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1. Voltage-gated potassium channels as a potential therapeutic target for the treatment of neurological and psychiatric disorders

Author

Isabel E. Faulkner, Rachael Z. Pajak, Michael K. Harte, Jocelyn D. Glazier, and Reinmar Hager

Subjects
Kv3 channels, schizophrenia, autism, epilepsy, ataxia, cognition, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Voltage-gated potassium channels are a widely distributed subgroup of potassium channels responsible for the efflux of potassium in the repolarisation of the cell membrane, and hence contribute to the latency and propagation of action potentials. As they are causal to synaptic transmission, alterations to the structure of these channels can lead to a variety of neurological and psychiatric diseases. The Kv3 subfamily of voltage-gated potassium channels are found on many neurons in the brain, including inhibitory interneurons where they contribute to fast-frequency firing. Changes to the firing ability of these interneurons can lead to an imbalance of inhibitory and excitatory neurotransmission. To date, we have little understanding of the mechanism by which excitatory and inhibitory inputs become imbalanced. This imbalance is associated with cognitive deficits seen across neurological and neuropsychiatric disorders, which are currently difficult to treat. In this review, we collate evidence supporting the hypothesis that voltage-gated potassium channels, specifically the Kv3 subfamily, are central to many neurological and psychiatric disorders, and may thus be considered as an effective drug target. The collective evidence provided by the studies reviewed here demonstrates that Kv3 channels may be amenable to novel treatments that modulate the activity of these channels, with the prospect of improved patient outcome.

Published
2024
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2. The impact of maternal immune activation on embryonic brain development

Author

Francesca McEwan, Jocelyn D. Glazier, and Reinmar Hager

Subjects
maternal immune activation, neurogenesis, neurodevelopment, proliferation, schizophrenia, autism spectrum disorder, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The adult brain is a complex structure with distinct functional sub-regions, which are generated from an initial pool of neural epithelial cells within the embryo. This transition requires a number of highly coordinated processes, including neurogenesis, i.e., the generation of neurons, and neuronal migration. These take place during a critical period of development, during which the brain is particularly susceptible to environmental insults. Neurogenesis defects have been associated with the pathogenesis of neurodevelopmental disorders (NDDs), such as autism spectrum disorder and schizophrenia. However, these disorders have highly complex multifactorial etiologies, and hence the underlying mechanisms leading to aberrant neurogenesis continue to be the focus of a significant research effort and have yet to be established. Evidence from epidemiological studies suggests that exposure to maternal infection in utero is a critical risk factor for NDDs. To establish the biological mechanisms linking maternal immune activation (MIA) and altered neurodevelopment, animal models have been developed that allow experimental manipulation and investigation of different developmental stages of brain development following exposure to MIA. Here, we review the changes to embryonic brain development focusing on neurogenesis, neuronal migration and cortical lamination, following MIA. Across published studies, we found evidence for an acute proliferation defect in the embryonic MIA brain, which, in most cases, is linked to an acceleration in neurogenesis, demonstrated by an increased proportion of neurogenic to proliferative divisions. This is accompanied by disrupted cortical lamination, particularly in the density of deep layer neurons, which may be a consequence of the premature neurogenic shift. Although many aspects of the underlying pathways remain unclear, an altered epigenome and mitochondrial dysfunction are likely mechanisms underpinning disrupted neurogenesis in the MIA model. Further research is necessary to delineate the causative pathways responsible for the variation in neurogenesis phenotype following MIA, which are likely due to differences in timing of MIA induction as well as sex-dependent variation. This will help to better understand the underlying pathogenesis of NDDs, and establish therapeutic targets.

Published
2023
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3. Clustering of cognitive phenotypes identifies susceptible and resilient offspring in a rat model of maternal immune activation and early-life stress

Author

Jarred M. Lorusso, Rebecca M. Woods, Francesca McEwan, Jocelyn D. Glazier, Joanna C. Neill, Michael Harte, and Reinmar Hager

Subjects
Maternal immune activation, Early life stress, Infection, Animal model, Two-hit, MIA, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Schizophrenia and other neurodevelopmental disorders often have very heterogeneous symptoms, especially regarding cognition: while some individuals may exhibit deficient cognition, others are relatively unaffected. Studies using developmental animal models often ignore phenotypic heterogeneity in favour of traditional treatment/control comparisons. This may result in resilient or unaffected individuals masking the effects of susceptible individuals if grouped together. Here, we used maternal immune activation and limited bedding and nesting, respectively, as a two-hit neurodevelopmental model for schizophrenia. Both factors reduced cognitive function in a novel object recognition (NOR) task. While we found treatment group effects on cognitive phenotypes, behavioural clustering identified three subpopulations exposed to either insult: those exhibiting ‘typical’ cognitive performance on the NOR, an intermediate phenotype, or a marked deficit. These clusters included offspring from each treatment group, although both intermediate and marked deficit clusters were composed primarily of offspring from treated groups. Clustering allowed stratification within treatment groups into ‘susceptible’ and ‘resilient’ individuals, while also identifying conserved phenotypes across treatment groups. Using unbiased cluster analyses in preclinical models can better characterize phenotypes and enables a better understanding of both face and construct validity of phenotypic heterogeneity. The use of unbiased clustering techniques may help identify potential markers associated with individual susceptibility and resilience in neurodevelopmental disorder models.

Published
2022
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4. Homocysteine Metabolism in Pregnancy and Developmental Impacts

Author

Stephen W. D’Souza and Jocelyn D. Glazier

Subjects
embryo, fetus, folate, methylation, neural tube defects, placenta, Biology (General), QH301-705.5
Abstract

Homocysteine is a metabolite generated by methionine cycle metabolism, comprising the demethylated derivative of methionine. Homocysteine can be metabolised by the transsulphuration pathway to cystathionine, which requires vitamin B6, or can undergo remethylation to methionine. Homocysteine remethylation to methionine is catalysed by methionine synthase activity which requires vitamin B12, regenerating methionine to allow synthesis of the universal methyl donor S-adenosylmethionine required for methylation and gene transcription regulation. The methyl-group donated for homocysteine remethylation comes from 5-methyltetrahydrofolate generated by the folate cycle, which allows tetrahydrofolate to be returned to the active folate pool for nucleotide biosynthesis. Therefore the integrated actions of the methionine and folate cycles, required to metabolise homocysteine, also perpetuate methylation and nucleotide synthesis, vitally important to support embryonic growth, proliferation and development. Dysregulated activities of these two interdependent metabolic cycles, arising from maternal suboptimal intake of nutrient co-factors such as folate and vitamin B12 or gene polymorphisms resulting in reduced enzymatic activity, leads to inefficient homocysteine metabolic conversion causing elevated concentrations, known as hyperhomocysteinemia. This condition is associated with multiple adverse pregnancy outcomes including neural tube defects (NTDs). Raised homocysteine is damaging to cellular function, binding to proteins thereby impairing their function, with perturbed homocysteine metabolism impacting negatively on embryonic development. This review discusses the “cross-talk” of maternal-fetal homocysteine interrelationships, describes the placental transport of homocysteine, homocysteine impacts on pregnancy outcomes, homocysteine and methylation effects linking to NTD risk and proposes a putative pathway for embryonic provision of folate and vitamin B12, homocysteine-modulating nutrients that ameliorate NTD risk.

Published
2022
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6. Maternal Immune Activation Induces Adolescent Cognitive Deficits Preceded by Developmental Perturbations in Cortical Reelin Signalling

Author

Rebecca M. Woods, Jarred M. Lorusso, Isabella Harris, Hager M. Kowash, Christopher Murgatroyd, Joanna C. Neill, Jocelyn D. Glazier, Michael Harte, and Reinmar Hager

Subjects
maternal immune activation, schizophrenia, Reelin, epigenetics, Microbiology, QR1-502
Abstract

Exposure to maternal immune activation (MIA) in utero significantly elevates the risk of developing schizophrenia and other neurodevelopmental disorders. To understand the biological mechanisms underlying the link between MIA and increased risk, preclinical animal models have focussed on specific signalling pathways in the brain that mediate symptoms associated with neurodevelopmental disorders such as cognitive dysfunction. Reelin signalling in multiple brain regions is involved in neuronal migration, synaptic plasticity and long-term potentiation, and has been implicated in cognitive deficits. However, how regulation of Reelin expression is affected by MIA across cortical development and associated cognitive functions remains largely unclear. Using a MIA rat model, here we demonstrate cognitive deficits in adolescent object-location memory in MIA offspring and reductions in Reln expression prenatally and in the adult prefrontal cortex. Further, developmental disturbances in gene/protein expression and DNA methylation of downstream signalling components occurred subsequent to MIA-induced Reelin dysregulation and prior to cognitive deficits. We propose that MIA-induced dysregulation of Reelin signalling contributes to the emergence of prefrontal cortex-mediated cognitive deficits through altered NMDA receptor function, resulting in inefficient long-term potentiation. Our data suggest a developmental window during which attenuation of Reelin signalling may provide a possible therapeutic target.

Published
2023
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7. Impact of maternal intermittent fasting during pregnancy on cardiovascular, metabolic and renal function in adult rat offspring

Author

Alaa Alkhalefah, Heather J. Eyre, Rezwana Hussain, Jocelyn D. Glazier, and Nick Ashton

Subjects
Medicine, Science
Abstract

Pregnant Muslim women are exempt from fasting during Ramadan; however a majority are reported to fast. The impact of this form of maternal intermittent fasting (IF) on fetal development and offspring health is not well defined. Using a rat model, we have shown previously that maternal IF results in fetal growth restriction accompanied by changes in placental nutrient transport function. The aim of this study was to assess cardiovascular, metabolic and renal function in adult offspring of IF-exposed dams. Food was withheld from Wistar rats from 17:00 to 09:00 daily throughout pregnancy; controls had ad libitum access to food. Birth weight was unaffected; however male IF pups grew more slowly up to 10 weeks of age (P < 0.01) whereas IF females matched their control counterparts. Systolic blood pressure (SBP), glucose tolerance and basal renal function at 14 weeks were not affected by IF exposure. When offered saline solutions (0.9–2.1%) to drink, females showed a greater salt preference than males (P < 0.01); however there were no differences between dietary groups. A separate group of pups was weaned onto a 4% NaCl diet. SBP increased in IF pups sooner, at 7 weeks (P < 0.01), than controls which became hypertensive from 10 weeks. Renal function did not appear to differ; however markers of renal injury were elevated in IF males (P < 0.05). Maternal IF does not affect resting cardiovascular, metabolic and renal function; but when challenged by dietary salt load male IF offspring are more prone to renal injury.

Published
2022

8. Maternal behaviours and adult offspring behavioural deficits are predicted by maternal TNFα concentration in a rat model of neurodevelopmental disorders

Author

Harry G. Potter, Hager M. Kowash, Rebecca M. Woods, Grace Revill, Amy Grime, Brendan Deeney, Matthew A. Burgess, Toby Aarons, Jocelyn D. Glazier, Joanna C. Neill, and Reinmar Hager

Subjects
Behavioral Neuroscience, Endocrine and Autonomic Systems, Immunology
Abstract

Exposure to inflammatory stressors during fetal development is a major risk factor for neurodevelopmental disorders (NDDs) in adult offspring. Maternal immune activation (MIA), induced by infection, causes an acute increase in pro-inflammatory cytokines which can increase the risk for NDDs directly by inducing placental and fetal brain inflammation, or indirectly through affecting maternal care behaviours thereby affecting postnatal brain development. Which of these two potential mechanisms dominates in increasing offspring risk for NDDs remains unclear. Here, we show that acute systemic maternal inflammation induced by the viral mimetic polyinosinic:polycytidylic acid (poly I:C) on gestational day 15 of rat pregnancy affects offspring and maternal behaviour, offspring cognition, and expression of NDD-relevant genes in the offspring brain. Dams exposed to poly I:C elicited an acute increase in the pro-inflammatory cytokine tumour necrosis factor (TNF; referred to here as TNFα), which predicted disruption of key maternal care behaviours. Offspring of poly I:C-treated dams showed early behavioural and adult cognitive deficits correlated to the maternal TNFα response, but, importantly, not with altered maternal care. We also found interacting effects of sex and treatment on GABAergic gene expression and DNA methylation in these offspring in a brain region-specific manner, including increased parvalbumin expression in the female adolescent frontal cortex. We conclude that the MIA-induced elevation of TNFα in the maternal compartment affects fetal neurodevelopment leading to altered offspring behaviour and cognition. Our results suggest that a focus on prenatal pathways affecting fetal neurodevelopment would provide greater insights into the mechanisms underpinning the TNFα-mediated genesis of altered offspring behaviour and cognition following maternal inflammation.

Published
2023
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9. The effect of Ramadan fasting during pregnancy on perinatal outcomes: a systematic review and meta-analysis

Author

Jocelyn D. Glazier, Dexter J. L. Hayes, Sabiha Hussain, Stephen W. D’Souza, Joanne Whitcombe, Alexander E. P. Heazell, and Nick Ashton

Subjects
Birth weight, Fasting, Placenta, Pregnancy, Ramadan, Gynecology and obstetrics, RG1-991
Abstract

Abstract Background Although exempt, many pregnant Muslim women partake in the daily fast during daylight hours during the month of Ramadan. In other contexts an impoverished diet during pregnancy impacts on birth weight. The aim of this systematic review was to determine whether Ramadan fasting by pregnant women affects perinatal outcomes. Primary outcomes investigated were perinatal mortality, preterm birth and small for gestational age (SGA) infants. Secondary outcomes investigated were stillbirth, neonatal death, maternal death, hypertensive disorders of pregnancy, gestational diabetes, congenital abnormalities, serious neonatal morbidity, birth weight, preterm birth and placental weight. Methods Systematic review and meta-analysis of observational studies and randomised controlled trials was conducted in EMBASE, MEDLINE, CINAHL, Web of Science, Google Scholar, the Health Management Information Consortium and Applied Social Sciences Index and Abstracts. Studies from any year were eligible. Studies reporting predefined perinatal outcomes in pregnancies exposed to Ramadan fasting were included. Cohort studies with no comparator group or that considered fasting outside pregnancy were excluded, as were studies assuming fasting practice based solely upon family name. Quality of included studies was assessed using the ROBINS-I tool for assessing risk of bias in non-randomised studies. Analyses were performed in STATA. Results From 375 records, 22 studies of 31,374 pregnancies were included, of which 18,920 pregnancies were exposed to Ramadan fasting. Birth weight was reported in 21 studies and was not affected by maternal fasting (standardised mean difference [SMD] 0.03, 95% CI 0.00 to 0.05). Placental weight was significantly lower in fasting mothers (SMD -0.94, 95% CI -0.97 to -0.90), although this observation was dominated by a single large study. No data were presented for perinatal mortality. Ramadan fasting had no effect on preterm delivery (odds ratio 0.99, 95% CI 0.72 to 1.37) based on 5600 pregnancies (1193 exposed to Ramadan fasting). Conclusions Ramadan fasting does not adversely affect birth weight although there is insufficient evidence regarding potential effects on other perinatal outcomes. Further studies are needed to accurately determine whether Ramadan fasting is associated with adverse maternal or neonatal outcome.

Published
2018
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10. Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders

Author

Rebecca M. Woods, Jarred M. Lorusso, Jennifer Fletcher, Heidi ElTaher, Francesca McEwan, Isabella Harris, Hager M. Kowash, Stephen W. D'Souza, Michael Harte, Reinmar Hager, and Jocelyn D. Glazier

Subjects
Cellular and Molecular Neuroscience, placenta, fetal brain, cytokine, pregnancy, infection, Epigenetic regulation
Abstract

Maternal infection during pregnancy, leading to maternal immune activation (mIA) and cytokine release, increases the offspring risk of developing a variety of neurodevelopmental disorders (NDDs), including schizophrenia. Animal models have provided evidence to support these mechanistic links, with placental inflammatory responses and dysregulation of placental function implicated. This leads to changes in fetal brain cytokine balance and altered epigenetic regulation of key neurodevelopmental pathways. The prenatal timing of such mIA-evoked changes, and the accompanying fetal developmental responses to an altered in utero environment, will determine the scope of the impacts on neurodevelopmental processes. Such dysregulation can impart enduring neuropathological changes, which manifest subsequently in the postnatal period as altered neurodevelopmental behaviours in the offspring. Hence, elucidation of the functional changes that occur at the molecular level in the placenta is vital in improving our understanding of the mechanisms that underlie the pathogenesis of NDDs. This has notable relevance to the recent COVID-19 pandemic, where inflammatory responses in the placenta to SARS-CoV-2 infection during pregnancy and NDDs in early childhood have been reported. This review presents an integrated overview of these collective topics and describes the possible contribution of prenatal programming through placental effects as an underlying mechanism that links to NDD risk, underpinned by altered epigenetic regulation of neurodevelopmental pathways.

Published
2023
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11. The Case for an EIC Theory Alliance

Author

R Abir, I Akushevich, T Altinoluk, D Anderle, B Balantekin, J Barata, M Battaglieri, C Bertulani, G Beuf, C Bissolotti, D Boer, M Boglione, R Boughezal, E Braaten, N Brambilla, V Braun, D Byer, F Celiberto, Y Chien, I Cloet, M Constantinou, W Cosyn, A Courtoy, A Czajka, U D'Alesio, I Danilkin, D Das, D de Florian, A Delgado, W Detmold, M Doring, A Dumitru, M Echevarria, R Edwards, G Eichmann, B El-Bennich, M Engelhardt, C Fernandez-Ramirez, C Fischer, G Fox, L Gamberg, M Garzelli, F Giacosa, G da Silveira, D Glazier, V Goncalves, S Grossberndt, F Guo, R Gupta, Y Hatta, M Hentschinski, A Blin, T Hobbs, A Ilyichev, J Jalilian-Marian, S Jia, Z Kang, B Karki, W Ke, V Khachatryan, D Kharzeev, S Klein, V Korepin, Y Kovchegov, S Kumano, W Lai, R Lebed, C Lee, K Lee, J Liao, H Lin, K Liu, S Liuti, C Lorce, H Mantysaari, V Mathieu, N Mathur, Y Mehtar-Tani, W Melnitchouk, E Mereghetti, A Metz, G Miller, S Mukherjee, S Munier, F Murgia, P Nadolsky, J Negele, D Neill, J Nemchik, E Nocera, V Okorokov, F Olness, B Pasquini, C Peng, P Petreczky, F Petriello, A Pilloni, B Pire, C Pisano, D Pitonyak, M Praszalowicz, A Prokudin, J Qiu, M Radici, J Rittenhouse West, A Rodas, S Rodini, J Rojo, F Salazar, E Santopinto, M Sargsian, N Sato, B Schenke, S Schindler, G Schnell, I Scimemi, J Segovia, K Semonov-Tian-Shansky, P Shanahan, D Shao, M Sievert, A Signori, R Singh, V Skokov, Q Song, S Srednyak, I Stewart, R Sufian, E Swanson, S Syritsyn, A Szczepaniak, Y Tawabutr, J Terry, T Toll, O Tomalak, F Twagirayezu, R Venugopalan, I Vitev, A Vladimirov, W Vogelsang, R Vogt, G Vujanovic, W Waalewijn, X Wang, B Xiao, Y Yang, X Yao, F Yuan, Y Zhao, and P Zurita

Published
2023
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12. ECCE sensitivity studies for single hadron transverse single spin asymmetry measurements

Author

R. Seidl, A. Vladimirov, D. Pitonyak, A. Prokudin, J.K. Adkins, Y. Akiba, A. Albataineh, M. Amaryan, I.C. Arsene, C. Ayerbe Gayoso, J. Bae, X. Bai, M.D. Baker, M. Bashkanov, R. Bellwied, F. Benmokhtar, V. Berdnikov, J.C. Bernauer, F. Bock, W. Boeglin, M. Borysova, E. Brash, P. Brindza, W.J. Briscoe, M. Brooks, S. Bueltmann, M.H.S. Bukhari, A. Bylinkin, R. Capobianco, W.-C. Chang, Y. Cheon, K. Chen, K.-F. Chen, K.-Y. Cheng, M. Chiu, T. Chujo, Z. Citron, E. Cline, E. Cohen, T. Cormier, Y. Corrales Morales, C. Cotton, J. Crafts, C. Crawford, S. Creekmore, C. Cuevas, J. Cunningham, G. David, C.T. Dean, M. Demarteau, S. Diehl, N. Doshita, R. Dupré, J.M. Durham, R. Dzhygadlo, R. Ehlers, L. El Fassi, A. Emmert, R. Ent, C. Fanelli, R. Fatemi, S. Fegan, M. Finger, J. Frantz, M. Friedman, I. Friscic, D. Gangadharan, S. Gardner, K. Gates, F. Geurts, R. Gilman, D. Glazier, E. Glimos, Y. Goto, N. Grau, S.V. Greene, A.Q. Guo, L. Guo, S.K. Ha, J. Haggerty, T. Hayward, X. He, O. Hen, D.W. Higinbotham, M. Hoballah, T. Horn, A. Hoghmrtsyan, P.-h.J. Hsu, J. Huang, G. Huber, A. Hutson, K.Y. Hwang, C.E. Hyde, M. Inaba, T. Iwata, H.S. Jo, K. Joo, N. Kalantarians, G. Kalicy, K. Kawade, S.J.D. Kay, A. Kim, B. Kim, C. Kim, M. Kim, Y. Kim, E. Kistenev, V. Klimenko, S.H. Ko, I. Korover, W. Korsch, G. Krintiras, S. Kuhn, C.-M. Kuo, T. Kutz, J. Lajoie, D. Lawrence, S. Lebedev, H. Lee, J.S.H. Lee, S.W. Lee, Y.-J. Lee, W. Li, W.B. Li, X. Li, Y.T. Liang, S. Lim, C.-H. Lin, D.X. Lin, K. Liu, M.X. Liu, K. Livingston, N. Liyanage, W.J. Llope, C. Loizides, E. Long, R.-S. Lu, Z. Lu, W. Lynch, S. Mantry, D. Marchand, M. Marcisovsky, C. Markert, P. Markowitz, H. Marukyan, P. McGaughey, M. Mihovilovic, R.G. Milner, A. Milov, Y. Miyachi, A. Mkrtchyan, P. Monaghan, R. Montgomery, D. Morrison, A. Movsisyan, H. Mkrtchyan, C. Munoz Camacho, M. Murray, K. Nagai, J. Nagle, I. Nakagawa, C. Nattrass, D. Nguyen, S. Niccolai, R. Nouicer, G. Nukazuka, M. Nycz, V.A. Okorokov, S. Orešić, J.D. Osborn, C. O’Shaughnessy, S. Paganis, Z. Papandreou, S.F. Pate, M. Patel, C. Paus, G. Penman, M.G. Perdekamp, D.V. Perepelitsa, H. Periera da Costa, K. Peters, W. Phelps, E. Piasetzky, C. Pinkenburg, I. Prochazka, T. Protzman, M.L. Purschke, J. Putschke, J.R. Pybus, R. Rajput-Ghoshal, J. Rasson, B. Raue, K.F. Read, K. Røed, R. Reed, J. Reinhold, E.L. Renner, J. Richards, C. Riedl, T. Rinn, J. Roche, G.M. Roland, G. Ron, M. Rosati, C. Royon, J. Ryu, S. Salur, N. Santiesteban, R. Santos, M. Sarsour, J. Schambach, A. Schmidt, N. Schmidt, C. Schwarz, J. Schwiening, A. Sickles, P. Simmerling, S. Sirca, D. Sharma, Z. Shi, T.-A. Shibata, C.-W. Shih, S. Shimizu, U. Shrestha, K. Slifer, K. Smith, D. Sokhan, R. Soltz, W. Sondheim, J. Song, I.I. Strakovsky, P. Steinberg, P. Stepanov, J. Stevens, J. Strube, P. Sun, X. Sun, K. Suresh, V. Tadevosyan, W.-C. Tang, S. Tapia Araya, S. Tarafdar, L. Teodorescu, D. Thomas, A. Timmins, L. Tomasek, N. Trotta, R. Trotta, T.S. Tveter, E. Umaka, A. Usman, H.W. van Hecke, C. Van Hulse, J. Velkovska, E. Voutier, P.K. Wang, Q. Wang, Y. Wang, D.P. Watts, N. Wickramaarachchi, L. Weinstein, M. Williams, C.-P. Wong, L. Wood, M.H. Wood, C. Woody, B. Wyslouch, Z. Xiao, Y. Yamazaki, Y. Yang, Z. Ye, H.D. Yoo, M. Yurov, N. Zachariou, W.A. Zajc, W. Zha, J.-L. Zhang, J.-X. Zhang, Y. Zhang, Y.-X. Zhao, X. Zheng, P. Zhuang, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
transverse spin dependent distribution and fragmentation functions, Nuclear and High Energy Physics, FOS: Physical sciences, lepton: scattering, transverse momentum dependence, hadron: transverse momentum, fragmentation function, x-dependence, High Energy Physics - Experiment, Sivers function, semi-inclusive DIS, High Energy Physics - Experiment (hep-ex), [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], parton, Collins, Instrumentation, transversity, spin: transverse, flavor, deep inelastic scattering: semi-inclusive reaction, positron p: deep inelastic scattering, nucleon: spin: transverse, sensitivity, Transverse spin dependent distribution and fragmentation functions, error: statistical, kinematics, ECCE detector feasibility studies, charge: tensor, numerical calculations: Monte Carlo, Semi-inclusive DIS, spin: asymmetry
Abstract

We performed feasibility studies for various single transverse spin measurements that are related to the Sivers effect, transversity and the tensor charge, and the Collins fragmentation function. The processes studied include semi-inclusive deep inelastic scattering (SIDIS) where single hadrons (pions and kaons) were detected in addition to the scattered DIS lepton. The data were obtained in {\sc pythia}6 and {\sc geant}4 simulated e+p collisions at 18 GeV on 275 GeV, 18 on 100, 10 on 100, and 5 on 41 that use the ECCE detector configuration. Typical DIS kinematics were selected, most notably $Q^2 > 1 $ GeV$^2$, and cover the $x$ range from $10^{-4}$ to $1$. The single spin asymmetries were extracted as a function of $x$ and $Q^2$, as well as the semi-inclusive variables $z$, and $P_T$. They are obtained in azimuthal moments in combinations of the azimuthal angles of the hadron transverse momentum and transverse spin of the nucleon relative to the lepton scattering plane. The initially unpolarized MonteCarlo was re-weighted in the true kinematic variables, hadron types and parton flavors based on global fits of fixed target SIDIS experiments and $e^+e^-$ annihilation data. The expected statistical precision of such measurements is extrapolated to 10 fb$^{-1}$ and potential systematic uncertainties are approximated given the deviations between true and reconstructed yields. The impact on the knowledge of the Sivers functions, transversity and tensor charges, and the Collins function has then been evaluated in the same phenomenological extractions as in the Yellow Report. The impact is found to be comparable to that obtained with the parameterized Yellow Report detector and shows that the ECCE detector configuration can fulfill the physics goals on these quantities., 22 pages, 22 figures, to be submitted to joint ECCE proposal NIM-A volume

Published
2023
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13. Search for e→τ charged lepton flavor violation at the EIC with the ECCE detector

Author

J.-L. Zhang, S. Mantry, J.K. Adkins, Y. Akiba, A. Albataineh, M. Amaryan, I.C. Arsene, C. Ayerbe Gayoso, J. Bae, X. Bai, M.D. Baker, M. Bashkanov, R. Bellwied, F. Benmokhtar, V. Berdnikov, J.C. Bernauer, F. Bock, W. Boeglin, M. Borysova, E. Brash, P. Brindza, W.J. Briscoe, M. Brooks, S. Bueltmann, M.H.S. Bukhari, A. Bylinkin, R. Capobianco, W.-C. Chang, Y. Cheon, K. Chen, K.-F. Chen, K.-Y. Cheng, M. Chiu, T. Chujo, Z. Citron, E. Cline, E. Cohen, T. Cormier, Y. Corrales Morales, C. Cotton, J. Crafts, C. Crawford, S. Creekmore, C. Cuevas, J. Cunningham, G. David, C.T. Dean, M. Demarteau, S. Diehl, N. Doshita, R. Dupré, J.M. Durham, R. Dzhygadlo, R. Ehlers, L. El Fassi, A. Emmert, R. Ent, C. Fanelli, R. Fatemi, S. Fegan, M. Finger, J. Frantz, M. Friedman, I. Friscic, D. Gangadharan, S. Gardner, K. Gates, F. Geurts, R. Gilman, D. Glazier, E. Glimos, Y. Goto, N. Grau, S.V. Greene, A.Q. Guo, L. Guo, S.K. Ha, J. Haggerty, T. Hayward, X. He, O. Hen, D.W. Higinbotham, M. Hoballah, T. Horn, A. Hoghmrtsyan, P.-h.J. Hsu, J. Huang, G. Huber, A. Hutson, K.Y. Hwang, C.E. Hyde, M. Inaba, T. Iwata, H.S. Jo, K. Joo, N. Kalantarians, G. Kalicy, K. Kawade, S.J.D. Kay, A. Kim, B. Kim, C. Kim, M. Kim, Y. Kim, E. Kistenev, V. Klimenko, S.H. Ko, I. Korover, W. Korsch, G. Krintiras, S. Kuhn, C.-M. Kuo, T. Kutz, J. Lajoie, D. Lawrence, S. Lebedev, H. Lee, J.S.H. Lee, S.W. Lee, Y.-J. Lee, W. Li, W.B. Li, X. Li, Y.T. Liang, S. Lim, C.-H. Lin, D.X. Lin, K. Liu, M.X. Liu, K. Livingston, N. Liyanage, W.J. Llope, C. Loizides, E. Long, R.-S. Lu, Z. Lu, W. Lynch, D. Marchand, M. Marcisovsky, C. Markert, P. Markowitz, H. Marukyan, P. McGaughey, M. Mihovilovic, R.G. Milner, A. Milov, Y. Miyachi, A. Mkrtchyan, H. Mkrtchyan, P. Monaghan, R. Montgomery, D. Morrison, A. Movsisyan, C. Munoz Camacho, M. Murray, K. Nagai, J. Nagle, I. Nakagawa, C. Nattrass, D. Nguyen, S. Niccolai, R. Nouicer, G. Nukazuka, M. Nycz, V.A. Okorokov, S. Orešić, J.D. Osborn, C. O’Shaughnessy, S. Paganis, Z. Papandreou, S.F. Pate, M. Patel, C. Paus, G. Penman, M.G. Perdekamp, D.V. Perepelitsa, H. Periera da Costa, K. Peters, W. Phelps, E. Piasetzky, C. Pinkenburg, I. Prochazka, T. Protzman, M.L. Purschke, J. Putschke, J.R. Pybus, R. Rajput-Ghoshal, J. Rasson, B. Raue, K.F. Read, K. Røed, R. Reed, J. Reinhold, E.L. Renner, J. Richards, C. Riedl, T. Rinn, J. Roche, G.M. Roland, G. Ron, M. Rosati, C. Royon, J. Ryu, S. Salur, N. Santiesteban, R. Santos, M. Sarsour, J. Schambach, A. Schmidt, N. Schmidt, C. Schwarz, J. Schwiening, R. Seidl, A. Sickles, P. Simmerling, S. Sirca, D. Sharma, Z. Shi, T.-A. Shibata, C.-W. Shih, S. Shimizu, U. Shrestha, K. Slifer, K. Smith, D. Sokhan, R. Soltz, W. Sondheim, J. Song, I.I. Strakovsky, P. Steinberg, P. Stepanov, J. Stevens, J. Strube, P. Sun, X. Sun, K. Suresh, V. Tadevosyan, W.-C. Tang, S. Tapia Araya, S. Tarafdar, L. Teodorescu, D. Thomas, A. Timmins, L. Tomasek, N. Trotta, R. Trotta, T.S. Tveter, E. Umaka, A. Usman, H.W. van Hecke, C. Van Hulse, J. Velkovska, E. Voutier, P.K. Wang, Q. Wang, Y. Wang, D.P. Watts, N. Wickramaarachchi, L. Weinstein, M. Williams, C.-P. Wong, L. Wood, M.H. Wood, C. Woody, B. Wyslouch, Z. Xiao, Y. Yamazaki, Y. Yang, Z. Ye, H.D. Yoo, M. Yurov, N. Zachariou, W.A. Zajc, W. Zha, J.-X. Zhang, Y. Zhang, Y.-X. Zhao, X. Zheng, and P. Zhuang

Subjects
Nuclear and High Energy Physics, Instrumentation
Published
2023
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14. Maternal immune activation in rodent models: A systematic review of neurodevelopmental changes in gene expression and epigenetic modulation in the offspring brain

Author

Harry G. Potter, Jarred Lorusso, Joanna C. Neill, Reinmar Hager, Jocelyn D. Glazier, and Rebecca M. Woods

Subjects
Epigenomics, Candidate gene, endocrine system diseases, Offspring, Cognitive Neuroscience, Gene Expression, Rodentia, Biology, Epigenesis, Genetic, Transcriptome, Behavioral Neuroscience, Pregnancy, Gene expression, medicine, Animals, Epigenetics, Gene, Behavior, Animal, Brain, medicine.disease, digestive system diseases, Disease Models, Animal, Poly I-C, Neuropsychology and Physiological Psychology, Schizophrenia, Prenatal Exposure Delayed Effects, Female, Neuroscience
Abstract

Maternal immune activation (mIA) during pregnancy is hypothesised to disrupt offspring neurodevelopment and predispose offspring to neurodevelopmental disorders such as schizophrenia. Rodent models of mIA have explored possible mechanisms underlying this paradigm and provide a vital tool for preclinical research. However, a comprehensive analysis of the molecular changes that occur in mIA-models is lacking, hindering identification of robust clinical targets. This systematic review assesses mIA-driven transcriptomic and epigenomic alterations in specific offspring brain regions. Across 118 studies, we focus on 88 candidate genes and show replicated changes in expression in critical functional areas, including elevated inflammatory markers, and reduced myelin and GABAergic signalling proteins. Further, disturbed epigenetic markers at nine of these genes support mIA-driven epigenetic modulation of transcription. Overall, our results demonstrate that current outcome measures have direct relevance for the hypothesised pathology of schizophrenia and emphasise the importance of mIA-models in contributing to the understanding of biological pathways impacted by mIA and the discovery of new drug targets.

Published
2021
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15. AI-assisted Optimization of the ECCE Tracking System at the Electron Ion Collider

Author

C. Fanelli, Z. Papandreou, K. Suresh, J.K. Adkins, Y. Akiba, A. Albataineh, M. Amaryan, I.C. Arsene, C. Ayerbe Gayoso, J. Bae, X. Bai, M.D. Baker, M. Bashkanov, R. Bellwied, F. Benmokhtar, V. Berdnikov, J.C. Bernauer, F. Bock, W. Boeglin, M. Borysova, E. Brash, P. Brindza, W.J. Briscoe, M. Brooks, S. Bueltmann, M.H.S. Bukhari, A. Bylinkin, R. Capobianco, W.-C. Chang, Y. Cheon, K. Chen, K.-F. Chen, K.-Y. Cheng, M. Chiu, T. Chujo, Z. Citron, E. Cline, E. Cohen, T. Cormier, Y. Corrales Morales, C. Cotton, J. Crafts, C. Crawford, S. Creekmore, C. Cuevas, J. Cunningham, G. David, C.T. Dean, M. Demarteau, S. Diehl, N. Doshita, R. Dupré, J.M. Durham, R. Dzhygadlo, R. Ehlers, L. El Fassi, A. Emmert, R. Ent, R. Fatemi, S. Fegan, M. Finger, J. Frantz, M. Friedman, I. Friscic, D. Gangadharan, S. Gardner, K. Gates, F. Geurts, R. Gilman, D. Glazier, E. Glimos, Y. Goto, N. Grau, S.V. Greene, A.Q. Guo, L. Guo, S.K. Ha, J. Haggerty, T. Hayward, X. He, O. Hen, D.W. Higinbotham, M. Hoballah, T. Horn, A. Hoghmrtsyan, P.-h.J. Hsu, J. Huang, G. Huber, A. Hutson, K.Y. Hwang, C.E. Hyde, M. Inaba, T. Iwata, H.S. Jo, K. Joo, N. Kalantarians, G. Kalicy, K. Kawade, S.J.D. Kay, A. Kim, B. Kim, C. Kim, M. Kim, Y. Kim, E. Kistenev, V. Klimenko, S.H. Ko, I. Korover, W. Korsch, G. Krintiras, S. Kuhn, C.-M. Kuo, T. Kutz, J. Lajoie, D. Lawrence, S. Lebedev, H. Lee, J.S.H. Lee, S.W. Lee, Y.-J. Lee, W. Li, W.B. Li, X. Li, Y.T. Liang, S. Lim, C.-H. Lin, D.X. Lin, K. Liu, M.X. Liu, K. Livingston, N. Liyanage, W.J. Llope, C. Loizides, E. Long, R.-S. Lu, Z. Lu, W. Lynch, S. Mantry, D. Marchand, M. Marcisovsky, C. Markert, P. Markowitz, H. Marukyan, P. McGaughey, M. Mihovilovic, R.G. Milner, A. Milov, Y. Miyachi, A. Mkrtchyan, P. Monaghan, R. Montgomery, D. Morrison, A. Movsisyan, H. Mkrtchyan, C. Munoz Camacho, M. Murray, K. Nagai, J. Nagle, I. Nakagawa, C. Nattrass, D. Nguyen, S. Niccolai, R. Nouicer, G. Nukazuka, M. Nycz, V.A. Okorokov, S. Orešić, J.D. Osborn, C. O’Shaughnessy, S. Paganis, S.F. Pate, M. Patel, C. Paus, G. Penman, M.G. Perdekamp, D.V. Perepelitsa, H. Periera da Costa, K. Peters, W. Phelps, E. Piasetzky, C. Pinkenburg, I. Prochazka, T. Protzman, M.L. Purschke, J. Putschke, J.R. Pybus, R. Rajput-Ghoshal, J. Rasson, B. Raue, K.F. Read, K. Røed, R. Reed, J. Reinhold, E.L. Renner, J. Richards, C. Riedl, T. Rinn, J. Roche, G.M. Roland, G. Ron, M. Rosati, C. Royon, J. Ryu, S. Salur, N. Santiesteban, R. Santos, M. Sarsour, J. Schambach, A. Schmidt, N. Schmidt, C. Schwarz, J. Schwiening, R. Seidl, A. Sickles, P. Simmerling, S. Sirca, D. Sharma, Z. Shi, T.-A. Shibata, C.-W. Shih, S. Shimizu, U. Shrestha, K. Slifer, K. Smith, D. Sokhan, R. Soltz, W. Sondheim, J. Song, I.I. Strakovsky, P. Steinberg, P. Stepanov, J. Stevens, J. Strube, P. Sun, X. Sun, V. Tadevosyan, W.-C. Tang, S. Tapia Araya, S. Tarafdar, L. Teodorescu, D. Thomas, A. Timmins, L. Tomasek, N. Trotta, R. Trotta, T.S. Tveter, E. Umaka, A. Usman, H.W. van Hecke, C. Van Hulse, J. Velkovska, E. Voutier, P.K. Wang, Q. Wang, Y. Wang, D.P. Watts, N. Wickramaarachchi, L. Weinstein, M. Williams, C.-P. Wong, L. Wood, M.H. Wood, C. Woody, B. Wyslouch, Z. Xiao, Y. Yamazaki, Y. Yang, Z. Ye, H.D. Yoo, M. Yurov, N. Zachariou, W.A. Zajc, W. Zha, J.-L. Zhang, J.-X. Zhang, Y. Zhang, Y.-X. Zhao, X. Zheng, P. Zhuang, HEP, INSPIRE, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
FOS: Computer and information sciences, Nuclear and High Energy Physics, Computer Science - Machine Learning, Physics - Instrumentation and Detectors, [PHYS.HEXP] Physics [physics]/High Energy Physics - Experiment [hep-ex], [PHYS.NEXP] Physics [physics]/Nuclear Experiment [nucl-ex], FOS: Physical sciences, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], [INFO] Computer Science [cs], Machine Learning (cs.LG), High Energy Physics - Experiment, Brookhaven Lab, High Energy Physics - Experiment (hep-ex), [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], [INFO]Computer Science [cs], tracking detector, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], evolutionary algorithms, Nuclear Experiment (nucl-ex), numerical calculations, Instrumentation, Nuclear Experiment, detector: design, Bayesian optimization, Instrumentation and Detectors (physics.ins-det), tracking, Computational Physics (physics.comp-ph), artificial intelligence, electron nucleus: colliding beams, [PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], ECCE, Physics - Computational Physics, electron ion collider, performance
Abstract

The Electron-Ion Collider (EIC) is a cutting-edge accelerator facility that will study the nature of the "glue" that binds the building blocks of the visible matter in the universe. The proposed experiment will be realized at Brookhaven National Laboratory in approximately 10 years from now, with detector design and R&D currently ongoing. Notably, EIC is one of the first large-scale facilities to leverage Artificial Intelligence (AI) already starting from the design and R&D phases. The EIC Comprehensive Chromodynamics Experiment (ECCE) is a consortium that proposed a detector design based on a 1.5T solenoid. The EIC detector proposal review concluded that the ECCE design will serve as the reference design for an EIC detector. Herein we describe a comprehensive optimization of the ECCE tracker using AI. The work required a complex parametrization of the simulated detector system. Our approach dealt with an optimization problem in a multidimensional design space driven by multiple objectives that encode the detector performance, while satisfying several mechanical constraints. We describe our strategy and show results obtained for the ECCE tracking system. The AI-assisted design is agnostic to the simulation framework and can be extended to other sub-detectors or to a system of sub-detectors to further optimize the performance of the EIC detector., 16 pages, 18 figures, 2 appendices, 3 tables

Published
2022
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16. Scientific Computing Plan for the ECCE Detector at the Electron Ion Collider

Author

J.C. Bernauer, C.T. Dean, C. Fanelli, J. Huang, K. Kauder, D. Lawrence, J.D. Osborn, C. Paus, J.K. Adkins, Y. Akiba, A. Albataineh, M. Amaryan, I.C. Arsene, C. Ayerbe Gayoso, J. Bae, X. Bai, M.D. Baker, M. Bashkanov, R. Bellwied, F. Benmokhtar, V. Berdnikov, F. Bock, W. Boeglin, M. Borysova, E. Brash, P. Brindza, W.J. Briscoe, M. Brooks, S. Bueltmann, M.H.S. Bukhari, A. Bylinkin, R. Capobianco, W.-C. Chang, Y. Cheon, K. Chen, K.-F. Chen, K.-Y. Cheng, M. Chiu, T. Chujo, Z. Citron, E. Cline, E. Cohen, T. Cormier, Y. Corrales Morales, C. Cotton, J. Crafts, C. Crawford, S. Creekmore, C. Cuevas, J. Cunningham, G. David, M. Demarteau, S. Diehl, N. Doshita, R. Dupré, J.M. Durham, R. Dzhygadlo, R. Ehlers, L. El Fassi, A. Emmert, R. Ent, R. Fatemi, S. Fegan, M. Finger, J. Frantz, M. Friedman, I. Friscic, D. Gangadharan, S. Gardner, K. Gates, F. Geurts, R. Gilman, D. Glazier, E. Glimos, Y. Goto, N. Grau, S.V. Greene, A.Q. Guo, L. Guo, S.K. Ha, J. Haggerty, T. Hayward, X. He, O. Hen, D.W. Higinbotham, M. Hoballah, T. Horn, A. Hoghmrtsyan, P.-h.J. Hsu, G. Huber, A. Hutson, K.Y. Hwang, C. Hyde, M. Inaba, T. Iwata, H.S. Jo, K. Joo, N. Kalantarians, G. Kalicy, K. Kawade, S.J.D. Kay, A. Kim, B. Kim, C. Kim, M. Kim, Y. Kim, E. Kistenev, V. Klimenko, S.H. Ko, I. Korover, W. Korsch, G. Krintiras, S. Kuhn, C.-M. Kuo, T. Kutz, J. Lajoie, S. Lebedev, H. Lee, J.S.H. Lee, S.W. Lee, Y.-J. Lee, W. Li, X. Li, Y.T. Liang, S. Lim, C.-h. Lin, D.X. Lin, K. Liu, M.X. Liu, K. Livingston, N. Liyanage, W.J. Llope, C. Loizides, E. Long, R.-S. Lu, Z. Lu, W. Lynch, D. Marchand, M. Marcisovsky, P. Markowitz, H. Marukyan, P. McGaughey, M. Mihovilovic, R.G. Milner, A. Milov, Y. Miyachi, A. Mkrtchyan, P. Monaghan, R. Montgomery, D. Morrison, A. Movsisyan, H. Mkrtchyan, C. Munoz Camacho, M. Murray, K. Nagai, J. Nagle, I. Nakagawa, C. Nattrass, D. Nguyen, S. Niccolai, R. Nouicer, G. Nukazuka, M. Nycz, V.A. Okorokov, S. Orešić, C. O’Shaughnessy, S. Paganis, Z. Papandreou, S.F. Pate, M. Patel, G. Penman, M.G. Perdekamp, D.V. Perepelitsa, H. Periera da Costa, K. Peters, W. Phelps, E. Piasetzky, C. Pinkenburg, I. Prochazka, T. Protzman, M.L. Purschke, J. Putschke, J.R. Pybus, R. Rajput-Ghoshal, J. Rasson, B. Raue, K. Read, K. Røed, R. Reed, J. Reinhold, E.L. Renner, J. Richards, C. Riedl, T. Rinn, J. Roche, G.M. Roland, G. Ron, M. Rosati, C. Royon, J. Ryu, S. Salur, N. Santiesteban, R. Santos, M. Sarsour, J. Schambach, A. Schmidt, N. Schmidt, C. Schwarz, J. Schwiening, R. Seidl, A. Sickles, P. Simmerling, S. Sirca, D. Sharma, Z. Shi, T.-A. Shibata, C.-W. Shih, S. Shimizu, U. Shrestha, K. Slifer, K. Smith, D. Sokhan, R. Soltz, W. Sondheim, J. Song, I.I. Strakovsky, P. Steinberg, P. Stepanov, J. Stevens, J. Strube, P. Sun, X. Sun, K. Suresh, V. Tadevosyan, W.-C. Tang, S. Tapia Araya, S. Tarafdar, L. Teodorescu, A. Timmins, L. Tomasek, N. Trotta, R. Trotta, T.S. Tveter, E. Umaka, A. Usman, H.W. van Hecke, C. Van Hulse, J. Velkovska, E. Voutier, P.K. Wang, Q. Wang, Y. Wang, D.P. Watts, N. Wickramaarachchi, L. Weinstein, M. Williams, C.-P. Wong, L. Wood, M.H. Wood, C. Woody, B. Wyslouch, Z. Xiao, Y. Yamazaki, Y. Yang, Z. Ye, H.D. Yoo, M. Yurov, N. Zachariou, W.A. Zajc, J. Zhang, Y. Zhang, Y.X. Zhao, X. Zheng, P. Zhuang, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Nuclear and High Energy Physics, Physics - Instrumentation and Detectors, data acquisition, FOS: Physical sciences, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], programming, computer: network, High Energy Physics - Experiment, Brookhaven Lab, High Energy Physics - Experiment (hep-ex), data compilation, quantum chromodynamics, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], [INFO]Computer Science [cs], [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Nuclear Experiment (nucl-ex), numerical calculations, Instrumentation, Nuclear Experiment, activity report, track data analysis, Instrumentation and Detectors (physics.ins-det), Computational Physics (physics.comp-ph), artificial intelligence, calibration, detector: proposed, electron nucleus: colliding beams, federated computing, data management, Physics - Computational Physics, electron ion collider, Jefferson Lab
Abstract

This is the arXiv pre-print which has not been peer reviewed. It is made available under a Creative Commons (CC BY) Attribution Lciense. The corrected version of record is available at: https://doi.org/10.1016/j.nima.2022.167859. Cite as: arXiv:2205.08607 [physics.ins-det] (or arXiv:2205.08607v1 [physics.ins-det] for this version) https://doi.org/10.48550/arXiv.2205.08607 Focus to learn more Journal reference: NIMA 1047, 167859 (2023) Related DOI: https://doi.org/10.1016/j.nima.2022.167859 Focus to learn more Submission history From: Joseph Osborn [view email] [v1] Tue, 17 May 2022 19:53:56 UTC (29,605 KB) Copyright © 2022 The Author(s). The Electron Ion Collider (EIC) is the next generation of precision QCD facility to be built at Brookhaven National Laboratory in conjunction with Thomas Jefferson National Laboratory. There are a significant number of software and computing challenges that need to be overcome at the EIC. During the EIC detector proposal development period, the ECCE consortium began identifying and addressing these challenges in the process of producing a complete detector proposal based upon detailed detector and physics simulations. In this document, the software and computing efforts to produce this proposal are discussed; furthermore, the computing and software model and resources required for the future of ECCE are described. Office of Nuclear Physics in the Office of Science in the Department of Energy, USA; National Science Foundation, USA; Los Alamos National Laboratory Laboratory Directed Research and Development (LDRD), USA 20200022DR.

Published
2022
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17. Passages and Afterworlds: Anthropological Perspectives on Death in the Caribbean

Author

Stephen D. Glazier

Subjects
060303 religions & theology, History, 060101 anthropology, Sociology and Political Science, Art history, 0601 history and archaeology, 06 humanities and the arts, 0603 philosophy, ethics and religion, Event (philosophy)
Abstract

In the Caribbean, afterworlds are very much connected to the worlds of the living, and for most Caribbean people, death is understood as a multi-stage process – not a one-time event. Spirits of the...

Published
2020
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18. Maternal immune activation in rats induces dysfunction of placental leucine transport and alters fetal brain growth

Author

Hager M. Kowash, Harry G. Potter, Rebecca M. Woods, Nick Ashton, Reinmar Hager, Joanna C. Neill, and Jocelyn D. Glazier

Subjects
Fetal Development, Poly I-C, Leucine, Pregnancy, Placenta, Animals, Brain, Cytokines, Female, General Medicine, Amino Acids, Rats
Abstract

Maternal infection during pregnancy increases the offspring risk of developing a variety of neurodevelopmental disorders (NDDs), including schizophrenia. While the mechanisms remain unclear, dysregulation of placental function is implicated. We hypothesised that maternal infection, leading to maternal immune activation and stimulated cytokine production, alters placental and yolk sac amino acid transport, affecting fetal brain development and thus NDD risk. Using a rat model of maternal immune activation induced by the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)), we investigated placental and yolk sac expression of system L amino acid transporter subtypes which transport several essential amino acids including branched-chain amino acids (BCAA), maternal and fetal BCAA concentration, placental 14C-leucine transport activity and associated impacts on fetal growth and development. Poly(I:C) treatment increased acutely maternal IL-6 and TNFα concentration, contrasting with IL-1β. Transcriptional responses for these pro-inflammatory cytokines were found in placenta and yolk sac following poly(I:C) treatment. Placental and yolk sac weights were reduced by poly(I:C) treatment, yet fetal body weight was unaffected, while fetal brain weight was increased. Maternal plasma BCAA concentration was reduced 24 h post-poly(I:C) treatment, yet placental, but not yolk sac, BCAA concentration was increased. Placental and yolk sac gene expression of Slc7a5, Slc7a8 and Slc43a2 encoding LAT1, LAT2 and LAT4 transporter subtypes, respectively, was altered by poly(I:C) treatment. Placental 14C-leucine transport was significantly reduced 24 h post-treatment, contrasting with a significant increase 6 days following poly(I:C) treatment. Maternal immune activation induces dysregulated placental transport of amino acids affecting fetal brain development, and NDD risk potential in offspring.

Published
2022
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19. Exclusive J/ψ detection and physics with ECCE

Author

X. Li, J.K. Adkins, Y. Akiba, A. Albataineh, M. Amaryan, I.C. Arsene, C. Ayerbe Gayoso, J. Bae, X. Bai, M.D. Baker, M. Bashkanov, R. Bellwied, F. Benmokhtar, V. Berdnikov, J.C. Bernauer, F. Bock, W. Boeglin, M. Borysova, E. Brash, P. Brindza, W.J. Briscoe, M. Brooks, S. Bueltmann, M.H.S. Bukhari, A. Bylinkin, R. Capobianco, W.-C. Chang, Y. Cheon, K. Chen, K.-F. Chen, K.-Y. Cheng, M. Chiu, T. Chujo, Z. Citron, E. Cline, E. Cohen, T. Cormier, Y. Corrales Morales, C. Cotton, J. Crafts, C. Crawford, S. Creekmore, C. Cuevas, J. Cunningham, G. David, C.T. Dean, M. Demarteau, S. Diehl, N. Doshita, R. Dupré, J.M. Durham, R. Dzhygadlo, R. Ehlers, L. El Fassi, A. Emmert, R. Ent, C. Fanelli, R. Fatemi, S. Fegan, M. Finger, J. Frantz, M. Friedman, I. Friscic, D. Gangadharan, S. Gardner, K. Gates, F. Geurts, R. Gilman, D. Glazier, E. Glimos, Y. Goto, N. Grau, S.V. Greene, A.Q. Guo, L. Guo, S.K. Ha, J. Haggerty, T. Hayward, X. He, O. Hen, D.W. Higinbotham, M. Hoballah, T. Horn, A. Hoghmrtsyan, P.-h.J. Hsu, J. Huang, G. Huber, A. Hutson, K.Y. Hwang, C.E. Hyde, M. Inaba, T. Iwata, H.S. Jo, K. Joo, N. Kalantarians, G. Kalicy, K. Kawade, S.J.D. Kay, A. Kim, B. Kim, C. Kim, M. Kim, Y. Kim, E. Kistenev, V. Klimenko, S.H. Ko, I. Korover, W. Korsch, G. Krintiras, S. Kuhn, C.-M. Kuo, T. Kutz, J. Lajoie, D. Lawrence, S. Lebedev, H. Lee, J.S.H. Lee, S.W. Lee, Y.-J. Lee, W. Li, W.B. Li, Y.T. Liang, S. Lim, C.-H. Lin, D.X. Lin, K. Liu, M.X. Liu, K. Livingston, N. Liyanage, W.J. Llope, C. Loizides, E. Long, R.-S. Lu, Z. Lu, W. Lynch, S. Mantry, D. Marchand, M. Marcisovsky, C. Markert, P. Markowitz, H. Marukyan, P. McGaughey, M. Mihovilovic, R.G. Milner, A. Milov, Y. Miyachi, A. Mkrtchyan, P. Monaghan, R. Montgomery, D. Morrison, A. Movsisyan, H. Mkrtchyan, C. Munoz Camacho, M. Murray, K. Nagai, J. Nagle, I. Nakagawa, C. Nattrass, D. Nguyen, S. Niccolai, R. Nouicer, G. Nukazuka, M. Nycz, V.A. Okorokov, S. Orešić, J.D. Osborn, C. O’Shaughnessy, S. Paganis, Z. Papandreou, S.F. Pate, M. Patel, C. Paus, G. Penman, M.G. Perdekamp, D.V. Perepelitsa, H. Periera da Costa, K. Peters, W. Phelps, E. Piasetzky, C. Pinkenburg, I. Prochazka, T. Protzman, M.L. Purschke, J. Putschke, J.R. Pybus, R. Rajput-Ghoshal, J. Rasson, B. Raue, K.F. Read, K. Røed, R. Reed, J. Reinhold, E.L. Renner, J. Richards, C. Riedl, T. Rinn, J. Roche, G.M. Roland, G. Ron, M. Rosati, C. Royon, J. Ryu, S. Salur, N. Santiesteban, R. Santos, M. Sarsour, J. Schambach, A. Schmidt, N. Schmidt, C. Schwarz, J. Schwiening, R. Seidl, A. Sickles, P. Simmerling, S. Sirca, D. Sharma, Z. Shi, T.-A. Shibata, C.-W. Shih, S. Shimizu, U. Shrestha, K. Slifer, K. Smith, D. Sokhan, R. Soltz, W. Sondheim, J. Song, I.I. Strakovsky, P. Steinberg, P. Stepanov, J. Stevens, J. Strube, P. Sun, X. Sun, K. Suresh, V. Tadevosyan, W.-C. Tang, S. Tapia Araya, S. Tarafdar, L. Teodorescu, D. Thomas, A. Timmins, L. Tomasek, N. Trotta, R. Trotta, T.S. Tveter, E. Umaka, A. Usman, H.W. van Hecke, C. Van Hulse, J. Velkovska, E. Voutier, P.K. Wang, Q. Wang, Y. Wang, D.P. Watts, N. Wickramaarachchi, L. Weinstein, M. Williams, C.-P. Wong, L. Wood, M.H. Wood, C. Woody, B. Wyslouch, Z. Xiao, Y. Yamazaki, Y. Yang, Z. Ye, H.D. Yoo, M. Yurov, N. Zachariou, W.A. Zajc, W. Zha, J.-L. Zhang, J.-X. Zhang, Y. Zhang, Y.-X. Zhao, X. Zheng, P. Zhuang, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Nuclear and High Energy Physics, Physics - Instrumentation and Detectors, Quarkonia, design, electron nucleon, Near threshold, EIC, pomeron, threshold, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], colliding beams, structure, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Nuclear Experiment, Instrumentation, detector, exchange, nucleus, Electron Ion Collider, nucleon, gluon, statistics, Exclusive, mass, production, ECCE, quarkonium, performance, photoproduction
Abstract

Exclusive heavy quarkonium photoproduction is one of the most popular processes in EIC, which has a large cross section and a simple final state. Due to the gluonic nature of the exchange Pomeron, this process can be related to the gluon distributions in the nucleus. The momentum transfer dependence of this process is sensitive to the interaction sites, which provides a powerful tool to probe the spatial distribution of gluons in the nucleus. Recently the problem of the origin of hadron mass has received lots of attention in determining the anomaly contribution $M_{a}$. The trace anomaly is sensitive to the gluon condensate, and exclusive production of quarkonia such as J/$\psi$ and $\Upsilon$ can serve as a sensitive probe to constrain it. In this paper, we present the performance of the ECCE detector for exclusive J/$\psi$ detection and the capability of this process to investigate the above physics opportunities with ECCE., Comment: 11 pages, 14 figures, 1 table

Published
2023
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20. Technical design report for the endcap disc DIRC

Author

F Davì, W Erni, B Krusche, M Steinacher, N Walford, H Liu, Z Liu, B Liu, X Shen, C Wang, J Zhao, M Albrecht, T Erlen, F Feldbauer, M Fink, V Freudenreich, M Fritsch, F H Heinsius, T Held, T Holtmann, I Keshk, H Koch, B Kopf, M Kuhlmann, M Kümmel, S Leiber, P Musiol, A Mustafa, M Pelizäus, A Pitka, G Reicherz, M Richter, C Schnier, T Schröder, S Sersin, L Sohl, C Sowa, M Steinke, T Triffterer, U Wiedner, R Beck, C Hammann, J Hartmann, B Ketzer, M Kube, M Rossbach, C Schmidt, R Schmitz, U Thoma, M Urban, A Bianconi, M Bragadireanu, D Pantea, W Czyzycki, M Domagala, G Filo, J Jaworowski, M Krawczyk, E Lisowski, F Lisowski, M Michałk, J Płażek, K Korcyl, A Kozela, P Kulessa, P Lebiedowicz, K Pysz, W Schäfer, A Szczurek, T Fiutowski, M Idzik, B Mindur, K Swientek, J Biernat, B Kamys, S Kistryn, G Korcyl, W Krzemien, A Magiera, P Moskal, W Przygoda, Z Rudy, P Salabura, J Smyrski, P Strzempek, A Wronska, I Augustin, R Böhm, I Lehmann, D Nicmorus Marinescu, L Schmitt, V Varentsov, M Al-Turany, A Belias, H Deppe, N Divani Veis, R Dzhygadlo, H Flemming, A Gerhardt, K Götzen, R Karabowicz, U Kurilla, D Lehmann, S Löchner, J Lühning, U Lynen, S Nakhoul, H Orth, K Peters, T Saito, G Schepers, C J Schmidt, C Schwarz, J Schwiening, A Täschner, M Traxler, B Voss, P Wieczorek, A Wilms, V Abazov, G Alexeev, V A Arefiev, V Astakhov, M Yu Barabanov, B V Batyunya, V Kh Dodokhov, A Efremov, A Fechtchenko, A Galoyan, G Golovanov, E K Koshurnikov, Y Yu Lobanov, V I Lobanov, V Malyshev, A G Olshevskiy, A A Piskun, A Samartsev, M G Sapozhnikov, N B Skachkov, A N Skachkova, E A Strokovsky, V Tokmenin, V Uzhinsky, A Verkheev, A Vodopianov, N I Zhuravlev, A Zinchenko, D Branford, D Glazier, D Watts, M Böhm, W Eyrich, A Lehmann, D Miehling, M Pfaffinger, S Stelter, F Uhlig, S Dobbs, K Seth, A Tomaradze, T Xiao, D Bettoni, A Ali, A Hamdi, M Krebs, F Nerling, V Akishina, S Gorbunov, I Kisel, G Kozlov, M Pugach, M Zyzak, N Bianchi, P Gianotti, C Guaraldo, V Lucherini, G Bracco, S Bodenschatz, K T Brinkmann, V Di Pietro, S Diehl, V Dormenev, M Düren, E Etzelmüller, K Föhl, M Galuska, T Geßler, E Gutz, C Hahn, A Hayrapetyan, M Kesselkaul, W Kühn, T Kuske, J S Lange, Y Liang, O Merle, V Metag, M Moritz, M Nanova, R Novotny, T Quagli, A Riccardi, J Rieke, M Schmidt, R Schnell, H Stenzel, M Strickert, U Thöring, T Wasem, B Wohlfahrt, H G Zaunick, E Tomasi-Gustafsson, D Ireland, G Rosner, B Seitz, P N Deepak, A Kulkarni, A Apostolou, M Babai, M Kavatsyuk, H Loehner, J Messchendorp, P Schakel, M Tiemens, J C van der Weele, S Vejdani, K Dutta, K Kalita, H Sohlbach, M Bai, L Bianchi, M Büscher, A Derichs, R Dosdall, A Erven, V Fracassi, A Gillitzer, F Goldenbaum, D Grunwald, L Jokhovets, G Kemmerling, H Kleines, A Lai, A Lehrach, M Mikirtychyants, S Orfanitski, D Prasuhn, E Prencipe, J Pütz, J Ritman, E Rosenthal, S Schadmand, T Sefzick, V Serdyuk, G Sterzenbach, T Stockmanns, P Wintz, P Wüstner, H Xu, Y Zhou, Z Li, X Ma, V Rigato, L Isaksson, P Achenbach, A Aycock, O Corell, A Denig, M Distler, M Hoek, W Lauth, H Merkel, U Müller, J Pochodzalla, S Sanchez, S Schlimme, C Sfienti, M Thiel, M Zambrana, H Ahmadi, S Ahmed, S Bleser, L Capozza, M Cardinali, A Dbeyssi, A Ehret, B Fröhlich, P Grasemann, S Haasler, D Izard, J Jorge, D Khaneft, R Klasen, R Kliemt, J Köhler, H H Leithoff, D Lin, F Maas, S Maldaner, M Michel, M C Mora Espí, C Morales Morales, C Motzko, O Noll, S Pflüger, D Rodríguez Piñeiro, M Steinen, E Walaa, S Wolff, I Zimmermann, A Fedorov, M Korzhik, O Missevitch, P Balanutsa, V Chernetsky, A Demekhin, A Dolgolenko, P Fedorets, A Gerasimov, V Goryachev, D Y Kirin, V A Matveev, A V Stavinskiy, A Balashoff, A Boukharov, O Malyshev, I Marishev, V Chandratre, V Datar, V Jha, H Kumawat, A K Mohanty, A Parmar, A K Rai, B Roy, G Sonika, C Fritzsch, S Grieser, A K Hergemöller, B Hetz, N Hüsken, A Khoukaz, J P Wessels, C Herold, K Khosonthongkee, C Kobdaj, A Limphirat, P Srisawad, Y Yan, A E Blinov, S Kononov, E A Kravchenko, E Antokhin, M Barnyakov, A Yu Barnyakov, K Beloborodov, V E Blinov, V S Bobrovnikov, I A Kuyanov, A P Onuchin, S Pivovarov, E Pyata, S Serednyakov, Y Tikhonov, R Kunne, D Marchand, B Ramstein, J van de Wiele, Y Wang, G Boca, V Burian, M Finger, A Nikolovova, M Pesek, M Peskova, M Pfeffer, I Prochazka, M Slunecka, P Gallus, V Jary, J Novy, M Tomasek, M Virius, V Vrba, V Abramov, N Belikov, S Bukreeva, A Davidenko, A Derevschikov, Y Goncharenko, V Grishin, V Kachanov, V Kormilitsin, A Levin, Y Melnik, N Minaev, V Mochalov, D Morozov, L Nogach, S Poslavskiy, A Ryazantsev, S Ryzhikov, P Semenov, I Shein, A Uzunian, A Vasiliev, A Yakutin, U Roy, B Yabsley, S Belostotski, G Gavrilov, A Izotov, S Manaenkov, O Miklukho, D Veretennikov, A Zhdanov, T Bäck, B Cederwall, K Makonyi, M Preston, P E Tegner, D Wölbing, S Godre, M P Bussa, S Marcello, S Spataro, F Iazzi, R Introzzi, A Lavagno, D Calvo, P De Remigis, A Filippi, G Mazza, A Rivetti, R Wheadon, A Martin, H Calen, W Ikegami Andersson, T Johansson, A Kupsc, P Marciniewski, M Papenbrock, J Pettersson, J Regina, K Schönning, M Wolke, J Diaz, V Pothodi Chackara, A Chlopik, G Kesik, D Melnychuk, B Slowinski, A Trzcinski, M Wojciechowski, S Wronka, B Zwieglinski, P Bühler, J Marton, D Steinschaden, K Suzuki, E Widmann, S Zimmermann, and J Zmeskal

Subjects
Subatomär fysik, Nuclear and High Energy Physics, PANDA, Subatomic Physics, Acceleratorfysik och instrumentering, technical design report, particle identification, Accelerator Physics and Instrumentation, Cherenkov detector
Abstract

PANDA (anti-proton annihiliation at Darmstadt) is planned to be one of the four main experiments at the future international accelerator complex FAIR (Facility for Antiproton and Ion Research) in Darmstadt, Germany. It is going to address fundamental questions of hadron physics and quantum chromodynamics using cooled antiproton beams with a high intensity and and momenta between 1.5 and 15 GeV/c. PANDA is designed to reach a maximum luminosity of 2 × 1032 cm−2 s. Most of the physics programs require an excellent particle identification (PID). The PID of hadronic states at the forward endcap of the target spectrometer will be done by a fast and compact Cherenkov detector that uses the detection of internally reflected Cherenkov light (DIRC) principle. It is designed to cover the polar angle range from 5° to 22° and to provide a separation power for the separation of charged pions and kaons up to 3 standard deviations (s.d.) for particle momenta up to 4 GeV/c in order to cover the important particle phase space. This document describes the technical design and the expected performance of the novel PANDA disc DIRC detector that has not been used in any other high energy physics experiment before. The performance has been studied with Monte-Carlo simulations and various beam tests at DESY and CERN. The final design meets all PANDA requirements and guarantees sufficient safety margins.

Published
2022

21. Homocysteine Metabolism in Pregnancy and Developmental Impacts

Author

Stephen W. D’Souza and Jocelyn D. Glazier

Subjects
Cell Biology, Developmental Biology
Abstract

Homocysteine is a metabolite generated by methionine cycle metabolism, comprising the demethylated derivative of methionine. Homocysteine can be metabolised by the transsulphuration pathway to cystathionine, which requires vitamin B6, or can undergo remethylation to methionine. Homocysteine remethylation to methionine is catalysed by methionine synthase activity which requires vitamin B12, regenerating methionine to allow synthesis of the universal methyl donor S-adenosylmethionine required for methylation and gene transcription regulation. The methyl-group donated for homocysteine remethylation comes from 5-methyltetrahydrofolate generated by the folate cycle, which allows tetrahydrofolate to be returned to the active folate pool for nucleotide biosynthesis. Therefore the integrated actions of the methionine and folate cycles, required to metabolise homocysteine, also perpetuate methylation and nucleotide synthesis, vitally important to support embryonic growth, proliferation and development. Dysregulated activities of these two interdependent metabolic cycles, arising from maternal suboptimal intake of nutrient co-factors such as folate and vitamin B12 or gene polymorphisms resulting in reduced enzymatic activity, leads to inefficient homocysteine metabolic conversion causing elevated concentrations, known as hyperhomocysteinemia. This condition is associated with multiple adverse pregnancy outcomes including neural tube defects (NTDs). Raised homocysteine is damaging to cellular function, binding to proteins thereby impairing their function, with perturbed homocysteine metabolism impacting negatively on embryonic development. This review discusses the “cross-talk” of maternal-fetal homocysteine interrelationships, describes the placental transport of homocysteine, homocysteine impacts on pregnancy outcomes, homocysteine and methylation effects linking to NTD risk and proposes a putative pathway for embryonic provision of folate and vitamin B12, homocysteine-modulating nutrients that ameliorate NTD risk.

Published
2021

23. Maternal intermittent fasting during pregnancy induces fetal growth restriction and down-regulated placental system A amino acid transport in the rat

Author

Franchesca D. Houghton, Jocelyn D. Glazier, Nick Ashton, Alaa Alkhalefah, Warwick B. Dunn, James W. Allwood, and Kate L. Parry

Subjects
0301 basic medicine, medicine.medical_specialty, Amino Acid Transport System A, Amino Acid Transport Systems, Placenta, Biology, Maternal Physiology, Fetal Development, 03 medical and health sciences, 0302 clinical medicine, Fetus, Pregnancy, Internal medicine, Intermittent fasting, medicine, Animals, Amino acid transporter, Rats, Wistar, 030219 obstetrics & reproductive medicine, Fetal Growth Retardation, Transplacental, General Medicine, Fasting, medicine.disease, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Gestation, Female
Abstract

During Ramadan, many pregnant Muslim women fast between dawn and sunset. Although the impacts of prolonged maternal intermittent fasting (IF) on fetal growth and placental function are under-researched, reported effects include reduced placental weight and birth weight. In the present study, pregnant Wistar rats were used to model repeated cycles of IF on fetal development and placental function and to examine sex-specific effects. In the IF group, food was withdrawn daily from 17:00 to 09:00 over 21 days of gestation, while the control group received food ad libitum. Both groups had free water access. IF dams consumed less food, had significantly reduced weight compared with controls, with reduced plasma glucose and amino acids. Both fetal sexes were significantly lighter in the IF group with reduced fetal plasma amino acids. Placental weights and morphology were unchanged. The profile of placental metabolites was altered in the IF group with sex-specific responses evident. Transplacental flux of 14C-methylaminoisobutyric acid ( 14C-MeAIB), a system A amino acid transporter substrate, was significantly reduced in both fetal sexes in the IF group. Sodium-dependent 14C-MeAIB uptake into isolated placental plasma membrane vesicles was unchanged. The gene expression of system A transporter Slc38a1, Slc38a2 and Slc38a4 was up-regulated in IF male placentas only. No changes were observed in placental SNAT1 and SNAT2 protein expression. Maternal IF results in detrimental impacts on maternal physiology and fetal development with changes in the placental and fetal metabolite profiles. Reduced placental system A transporter activity may be responsible for fetal growth restriction in both sexes.

Published
2021
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24. Differential expression of system L amino acid transporter subtypes in rat placenta and yolk sac

Author

Nick Ashton, Jocelyn D. Glazier, Wejdan H. Owaydhah, François Verrey, University of Zurich, and Glazier, Jocelyn D

Subjects
Male, 0301 basic medicine, Placenta, Endodermal cell, 10052 Institute of Physiology, 1309 Developmental Biology, 0302 clinical medicine, Pregnancy, Yolk Sac, chemistry.chemical_classification, 030219 obstetrics & reproductive medicine, biology, Chemistry, Fusion Regulatory Protein 1, Light Chains, Gene Expression Regulation, Developmental, Obstetrics and Gynecology, Cell biology, Amino acid, medicine.anatomical_structure, embryonic structures, CD98, Female, Amino Acid Transport System y+, 610 Medicine & health, Large Neutral Amino Acid-Transporter 1, Junctional zone, 03 medical and health sciences, medicine, Animals, Amino acid transporter, Rats, Wistar, Yolk sac, Labyrinth, Adaptor Proteins, Signal Transducing, Fetus, System L, LAT2, 2729 Obstetrics and Gynecology, LAT4, 2743 Reproductive Medicine, LAT1, Rats, 030104 developmental biology, Reproductive Medicine, Cytoplasm, Amino Acid Transport System L, biology.protein, 570 Life sciences, Developmental Biology
Abstract

Introduction: Amino acid transport across the placenta is crucial for fetal growth. In rodent models, the visceral yolk sac (referred to as yolk sac hereafter) is also likely to contribute to fetal amino acid provision. System L amino acid transporters mediate the transport of essential amino acids. System L activity is mediated by light chains LAT1 (Slc7a5) and LAT2 (Slc7a8) which form functional complexes by heterodimeric linkage to CD98 (Slc3a2). LAT4 (Slc43a2) is monomeric, possessing overlapping amino acid substrate specificity with LAT1 and LAT2. Methods: This study investigates the expression of these LAT subtypes in fetus-matched rat placenta and yolk sac. Results: Slc7a5, Slc7a8 and Slc43a2 transcripts were expressed in placenta and yolk sac with similar expression patterns between sexes. LAT1 expression was significantly higher in placenta than yolk sac. Conversely, LAT2 and LAT4 expression was significantly higher in yolk sac than placenta; CD98 expression was comparable. LAT1, LAT2, LAT4 and CD98 were distributed to rat placental labyrinth zone (LZ) and junctional zone (JZ). LAT1 and LAT4 demonstrated higher expression in LZ, whilst LAT2 was more intensely distributed to JZ. LAT1, LAT2, LAT4 and CD98 were expressed in yolk sac, with punctate LAT1 staining to endodermal cell cytoplasm, contrasting with the intense LAT2, LAT4 and CD98 endodermal cell basolateral distribution, accounting for greater LAT2 and LAT4 expression in yolk sac compared to placenta. Conclusion: LAT1, LAT2 and LAT4 are expressed in rat placenta and yolk sac implicating a combined role for these LAT subtypes in supporting fetal growth and development.

Published
2021
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26. Does malaria affect placental development? Evidence from in vitro models.

Author

Alexandra J Umbers, Danielle I Stanisic, Maria Ome, Regina Wangnapi, Sarah Hanieh, Holger W Unger, Leanne J Robinson, Elvin Lufele, Francesca Baiwog, Peter M Siba, Christopher L King, James G Beeson, Ivo Mueller, John D Aplin, Jocelyn D Glazier, and Stephen J Rogerson

Subjects
Medicine, Science
Abstract

BACKGROUND:Malaria in early pregnancy is difficult to study but has recently been associated with fetal growth restriction (FGR). The pathogenic mechanisms underlying malarial FGR are poorly characterized, but may include impaired placental development. We used in vitro methods that model migration and invasion of placental trophoblast into the uterine wall to investigate whether soluble factors released into maternal blood in malaria infection might impair placental development. Because trophoblast invasion is enhanced by a number of hormones and chemokines, and is inhibited by pro-inflammatory cytokines, many of which are dysregulated in malaria in pregnancy, we further compared concentrations of these factors in blood between malaria-infected and uninfected pregnancies. METHODOLOGY/PRINCIPAL FINDINGS:We measured trophoblast invasion, migration and viability in response to treatment with serum or plasma from two independent cohorts of Papua New Guinean women infected with Plasmodium falciparum or Plasmodium vivax in early pregnancy. Compared to uninfected women, serum and plasma from women with P. falciparum reduced trophoblast invasion (P = .06) and migration (P = .004). P. vivax infection did not alter trophoblast migration (P = .64). The P. falciparum-specific negative effect on placental development was independent of trophoblast viability, but associated with high-density infections. Serum from P. falciparum infected women tended to have lower levels of trophoblast invasion promoting hormones and factors and higher levels of invasion-inhibitory inflammatory factors. CONCLUSION/SIGNIFICANCE:We demonstrate that in vitro models of placental development can be adapted to indirectly study the impact of malaria in early pregnancy. These infections could result in impaired trophoblast invasion with reduced transformation of maternal spiral arteries due to maternal hormonal and inflammatory disturbances, which may contribute to FGR by limiting the delivery of maternal blood to the placenta. Future prevention strategies for malaria in pregnancy should include protection in the first half of pregnancy.

Published
2013
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27. Maternal Inositol Status and Neural Tube Defects: A Role for the Human Yolk Sac in Embryonic Inositol Delivery?

Author

Andrew J. Copp, Jocelyn D. Glazier, Stephen W D'Souza, and Nicholas D. E. Greene

Subjects
0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, myo-inositol, placenta, Medicine (miscellaneous), Review, 030105 genetics & heredity, Biology, folate, 03 medical and health sciences, chemistry.chemical_compound, AcademicSubjects/MED00060, Folic Acid, Pregnancy, medicine, Humans, Inositol, Neural Tube Defects, Yolk sac, Spinal Dysraphism, Yolk Sac, Fetus, Nutrition and Dietetics, Neural tube defect, Embryogenesis, Neural tube, medicine.disease, Embryonic stem cell, Cell biology, fetus, 030104 developmental biology, medicine.anatomical_structure, chemistry, polyol, Female, Food Science
Abstract

Supplementation with myo-inositol during the periconceptional period of pregnancy may ameliorate the recurrence risk of having a fetus affected by a neural tube defect (NTD; e.g., spina bifida). This could be of particular importance in providing a means for preventing NTDs that are unresponsive to folic acid. This review highlights the characteristics of inositol and describes the role of myo-inositol in the prevention of NTDs in rodent studies and the evidence for its efficacy in reducing NTD risk in human pregnancy. The possible reduction in NTD risk by maternal myo-inositol implies functional and developmentally important maternal–embryonic inositol interrelationships and also suggests that embryonic uptake of myo-inositol is crucial for embryonic development. The establishment of active myo-inositol cellular uptake mechanisms in the embryonic stages of human pregnancy, when the neural tube is closing, is likely to be an important determinant of normal development. We draw attention to the generation of materno-fetal inositol concentration gradients and relationships, and outline a transport pathway by which myo-inositol may be delivered to the early developing human embryo. These considerations provide novel insights into the mechanisms that may underpin inositol's ability to confer embryonic developmental benefit.

Published
2020

28. An Ethnography of a Vodu Shrine in Southern Togo: Of Spirit, Slave and Sea, by Eric J. Montgomery and Christian N. Vannier, Leiden, Brill, 2017, ix+306 pp., US$141.00 (hardback), ISBN 978 9 0043 4108 1

Author

Stephen D. Glazier

Subjects
History, 060101 anthropology, 060102 archaeology, Sociology and Political Science, biology, media_common.quotation_subject, Brill, 06 humanities and the arts, Art, biology.organism_classification, Ethnography, 0601 history and archaeology, Theology, media_common
Abstract

Vodu means ‘spirit’ in the Ewe language (Ellis 1890). It has been spelled variously in English (Vodon, Vodoun, Vodou, Voudou, Voodoo, etc.). The religion is widespread in southern and central Togo ...

Published
2018
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29. Edith Lucy Brocklesby Turner (1921-2016)

Author

Stephen D. Glazier

Subjects
060101 anthropology, 060102 archaeology, Arts and Humanities (miscellaneous), Anthropology, media_common.quotation_subject, 0601 history and archaeology, 06 humanities and the arts, Art, media_common
Published
2018
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30. Relevant assay to study the adhesion of Plasmodium falciparum-infected erythrocytes to the placental epithelium.

Author

Philippe Boeuf, Wina Hasang, Eric Hanssen, Jocelyn D Glazier, and Stephen J Rogerson

Subjects
Medicine, Science
Abstract

In placental malaria, Plasmodium falciparum-infected erythrocytes adhere to the apical plasma membrane of the placental epithelium, triggering an impairment of placental function detrimental to the fetus. The design of anti-adhesion intervention strategies requires a detailed understanding of the mechanisms involved. However, most adhesion assays lack in vivo relevance and are hardly quantitative. Here, we describe a flow cytometry-based adhesion assay that is fully relevant by using apical epithelial plasma membrane vesicles as the adhesion matrix, and being applicable to infected erythrocytes directly isolated from patients. Adhesion is measured both as the percentage of pathogens bound to epithelial membrane vesicles as well as the mean number of vesicles bound per infected erythrocytes. We show that adhesins alternative to those currently identified could be involved. This demonstrates the power of this assay to advance our understanding of epithelial adhesion of infected erythrocytes and in the design of intervention strategies.

Published
2011
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31. Undue Influence and Vulnerable Adults

Author

Sandra D. Glazier, Thomas M. Dixon, Thomas F. Sweeney, Sandra D. Glazier, Thomas M. Dixon, and Thomas F. Sweeney

Subjects
Wills--United States, Undue influence--United States
Abstract

Age-related issues, including diminished capacity, can be a significant indicator of the potential vulnerability of a client to undue influence, and also an indicator that our population as a whole is aging. Elder abuse has been called'the crime of the 21st century.'Undue influence is a form of financial abuse of the elderly, with the large number of reported cases and estimated $1.17 billion in damages just the tip of the iceberg.Looking at the topic from a legal perspective, Undue Influence and Vulnerable Adults addresses both the role and the importance of the attorney when representing a vulnerable adult. The book's authors, who each command extensive experience in the area, explain the relevant considerations and provide strategies when litigation is required. Their practical and legal advice on issues will assist planners identify issues and then create effective plans for vulnerable adults that may better withstand attack.Undue Influence and Vulnerable Adults also helps readers understand the options and potential consequences of proactive waivers and permissions for release of information as well as the potential importance of being able to initiate contact with family or other trusted advisors when concerns about capacity and/or undue influence subsequently arise. In addition, the authors provide strategies from a litigation perspective on handling efforts to invalidate as well as defend instruments claimed to be the result of undue influence.Table of ContentsPreambleIntroductionChapter 1: Ethical Considerations When Representing Vulnerable AdultsChapter 2: To Understand Undue Influence, One Needs to Understand CapacityChapter 3: What Is Undue Influence?Chapter 4: Evidence of Undue InfluenceChapter 5: Fraud and Duress Are Different Than Undue InfluenceChapter 6: The Presumption of Undue InfluenceChapter 7: Rebutting the PresumptionChapter 8: No-Contest Clauses and the Importance of Probable CauseChapter 9: A Litigation PerspectiveChapter 10: Using Experts and Understanding the Medical EvidenceChapter 11: The Attorney-Client PrivilegeChapter 12: Video Recording, Electronic Wills, and Remote Witnessing and NotarizationIndex

Published
2022

33. Caribbean Ethncty Revisited 4#

Author

Stephen D. Glazier and Stephen D. Glazier

Subjects
GN495.6
Abstract

This collection of papers by a number of eminent anthropologists explores the patterns of ethnicity in the Caribbean. A valuable contribution to current literature in the field, these papers greatly increase our understanding of Caribbean societies. The variety of theoretical approaches to the processes that shaped Caribbean ethnic relations make this work a fascinating and vital study of the region as a whole.

Published
2021

35. Withdrawal: Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel disease: Evidence for involvement of the transcription factor Egr-1

Author

Kazuhiko Yoshimatsu, Kotha Subbaramaiah, Robert A. Soslow, Andrew J. Dannenberg, Dragan Golijanin, Hiroaki Naraba, Tadashi Tanabe, Kenneth D. Glazier, Ellen Scherl, and Kiron M. Das

Subjects
Chemistry, medicine, Cell Biology, Pharmacology, Microsomal Prostaglandin E Synthase-1, medicine.disease, Molecular Biology, Biochemistry, Inflammatory bowel disease, Transcription factor
Published
2020

36. Poly(I:C) source, molecular weight and endotoxin contamination affect dam and prenatal outcomes, implications for models of maternal immune activation

Author

Michelle E. Edye, Jocelyn D. Glazier, Joanna C. Neill, Reinmar Hager, Eric Prinssen, Hager Kowash, Harry G. Potter, and S. Bandinelli

Subjects
sex differences, 0301 basic medicine, Male, endotoxin, placenta, Litter Size, Immunology, Andrology, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Fetus, fetal brain, Pregnancy, Placenta, medicine, Animals, Rats, Wistar, Interleukin 6, I²C, IL-6, maternal immune activation, biology, Behavior, Animal, Endocrine and Autonomic Systems, Fetal Body Weight, Reproducibility of Results, molecular weight, Phenotype, Infectious Disease Transmission, Vertical, Rats, Endotoxins, fetus, 030104 developmental biology, medicine.anatomical_structure, Poly I-C, Maternal Exposure, Neurodevelopmental Disorders, Prenatal Exposure Delayed Effects, biology.protein, Gestation, Cytokines, Female, Endotoxin Contamination, C) [poly(I], litter size, 030217 neurology & neurosurgery
Abstract

The viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) is increasingly used to induce maternal immune activation (mIA) to model neurodevelopmental disorders (NDDs). Robust and reproducible phenotypes across studies are essential for the generation of models that will enhance our understanding of NDDs and enable the development of improved therapeutic strategies. However, differences in mIA-induced phenotypes using poly(I:C) have been widely observed, and this has prompted the reporting of useful and much needed methodological guidelines. Here, we perform a detailed investigation of molecular weight and endotoxin variations in poly(I:C) procured from two of the most commonly used suppliers, Sigma and InvivoGen. We demonstrate that endotoxin contamination and molecular weight differences in poly(I:C) composition lead to considerable variability in maternal IL-6 response in rats treated on gestational day (GD)15 and impact on fetal outcomes. Specifically, both endotoxin contamination and molecular weight predicted reductions in litter size on GD21. Further, molecular weight predicted a reduction in placental weight at GD21. While fetal body weight at GD21 was not affected by poly(I:C) treatment, male fetal brain weight was significantly reduced by poly(I:C), dependent on supplier. Our data are in agreement with recent reports of the importance of poly(I:C) molecular weight, and extend this work to demonstrate a key role of endotoxin on relevant phenotypic outcomes. We recommend that the source and batch numbers of poly(I:C) used should always be stated and that molecular weight variability and endotoxin contamination should be minimised for more robust mIA modelling.

Published
2019
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37. A proposed model for paradigmatic relations within an emergent discipline

Author

Jack D. Glazier

Subjects
Paradigmatic change, Theory, Disciplinary change, Symbolic interactionism, Library and information science education, Thomas Kuhn's paradigmatic revolution, Information resources (General), ZA3040-5185
Abstract

This article is the vehicle for purposing a model for mapping the processual change associated with disciplinary and paradigmatic development. Change of this sort is contingent on the degree of consistency achieved within theory groups. Consistency, in this case, is equated theory and paradigm dominance. The symbolic interactionist tradition supplies the assumptions on which the model is grounded Examination of the model is accomplished by contrasting it with Thomas Kuhn's theory. The recent history of library and information science education in the U.S. serves as context and exemplar for application of the model

Published
2002

38. Propuesta de un modelo de las relaciones de los paradigmas en una disciplina emergente

Author

Jack D. Glazier

Subjects
cambios de paradigma, teoría, cambio disciplinar, interaccionismo simbólico, Enseñanza de la Biblioteconomía y Documentación, Teoría de las Revoluciones Científicas de Thomas Kuhn, Information resources (General), ZA3040-5185
Abstract

Este artículo sirve de vehículo para la propuesta de un modelo que describe los cambios progresivos relacionados con el desarrollo de disciplinas y paradigmas. Este tipo de cambios depende directamente del grado de consistencia alcanzado por los grupos teóricos. Consistencia, en este caso, equivale al predominio de una teoría y de un paradigma. Los presupuestos en que se basa nuestro modelo son aportados por el interaccionismo simbólico tradicional. El análisis de este modelo se realiza mediante su comparación con la teoría de Thomas Kuhn. La historia reciente de la enseñanza de la Biblioteconomía y Documentación en EEUU sirve como contexto y de ejemplo sobre el cual aplicar este modelo

Published
2002

40. Study of doubly strange systems using stored antiprotons

Author

B. Singh, W. Erni, B. Krusche, M. Steinacher, N. Walford, B. Liu, H. Liu, Z. Liu, X. Shen, C. Wang, J. Zhao, M. Albrecht, T. Erlen, M. Fink, F. Heinsius, T. Held, T. Holtmann, S. Jasper, I. Keshk, H. Koch, B. Kopf, M. Kuhlmann, M. Kümmel, S. Leiber, M. Mikirtychyants, P. Musiol, A. Mustafa, M. Pelizäus, J. Pychy, M. Richter, C. Schnier, T. Schröder, C. Sowa, M. Steinke, T. Triffterer, U. Wiedner, M. Ball, R. Beck, C. Hammann, B. Ketzer, M. Kube, P. Mahlberg, M. Rossbach, C. Schmidt, R. Schmitz, U. Thoma, M. Urban, D. Walther, C. Wendel, A. Wilson, A. Bianconi, M. Bragadireanu, M. Caprini, D. Pantea, B. Patel, W. Czyzycki, M. Domagala, G. Filo, J. Jaworowski, M. Krawczyk, E. Lisowski, F. Lisowski, M. Michałek, P. Poznański, J. Płażek, K. Korcyl, A. Kozela, P. Kulessa, P. Lebiedowicz, K. Pysz, W. Schäfer, A. Szczurek, T. Fiutowski, M. Idzik, B. Mindur, D. Przyborowski, K. Swientek, J. Biernat, B. Kamys, S. Kistryn, G. Korcyl, W. Krzemien, A. Magiera, P. Moskal, A. Psyzniak, Z. Rudy, P. Salabura, J. Smyrski, P. Strzempek, A. Wronska, I. Augustin, R. Böhm, I. Lehmann, D. Nicmorus Marinescu, L. Schmitt, V. Varentsov, M. Al-Turany, A. Belias, H. Deppe, R. Dzhygadlo, A. Ehret, H. Flemming, A. Gerhardt, K. Götzen, A. Gromliuk, L. Gruber, R. Karabowicz, R. Kliemt, M. Krebs, U. Kurilla, D. Lehmann, S. Löchner, J. Lühning, U. Lynen, H. Orth, M. Patsyuk, K. Peters, T. Saito, G. Schepers, C.J. Schmidt, C. Schwarz, J. Schwiening, A. Täschner, M. Traxler, C. Ugur, B. Voss, P. Wieczorek, A. Wilms, M. Zühlsdorf, V.M. Abazov, G. Alexeev, A. Arefiev, V.I. Astakhov, M.Yu. Barabanov, B.V. Batyunya, Yu.I. Davydov, V.Kh. Dodokhov, A.A. Efremov, A. Fechtchenko, A.G. Fedunov, A. Galoyan, S. Grigoryan, E.K. Koshurnikov, V.I. Lobanov, Y.Yu. Lobanov, A.F. Makarov, L.V. Malinina, V.L. Malyshev, A. Olshevskiy, E. Perevalova, A.A. Piskun, T. Pocheptsov, G. Pontecorvo, V. Rodionov, Y. Rogov, R. Salmin, A. Samartsev, M.G. Sapozhnikov, G. Shabratova, N.B. Skachkov, A.N. Skachkova, E.A. Strokovsky, M. Suleimanov, R. Teshev, V. Tokmenin, V. Uzhinsky, A. Vodopyanov, S.A. Zaporozhets, N.I. Zhuravlev, A.G. Zorin, D. Branford, D. Glazier, D. Watts, M. Böhm, A. Britting, W. Eyrich, A. Lehmann, M. Pfaffinger, F. Uhlig, S. Dobbs, K. Seth, A. Tomaradze, T. Xiao, D. Bettoni, V. Carassiti, A. Cotta Ramusino, P. Dalpiaz, A. Drago, E. Fioravanti, I. Garzia, M. Savriè, V. Akishina, I. Kisel, G. Kozlov, M. Pugach, M. Zyzak, P. Gianotti, C. Guaraldo, V. Lucherini, A. Bersani, G. Bracco, M. Macri, R.F. Parodi, K. Biguenko, K. Brinkmann, V. Di Pietro, S. Diehl, V. Dormenev, P. Drexler, M. Düren, E. Etzelmüller, M. Galuska, E. Gutz, C. Hahn, A. Hayrapetyan, M. Kesselkaul, W. Kühn, T. Kuske, J.S. Lange, Y. Liang, V. Metag, M. Nanova, S. Nazarenko, R. Novotny, T. Quagli, S. Reiter, J. Rieke, C. Rosenbaum, M. Schmidt, R. Schnell, H. Stenzel, U. Thöring, M. Ullrich, M.N. Wagner, T. Wasem, B. Wohlfarth, H. Zaunick, D. Ireland, G. Rosner, B. Seitz, P.N. Deepak, A. Kulkarni, A. Apostolou, M. Babai, M. Kavatsyuk, P. Lemmens, M. Lindemulder, H. Loehner, J. Messchendorp, P. Schakel, H. Smit, M. Tiemens, J.C. van der Weele, R. Veenstra, S. Vejdani, K. Dutta, K. Kalita, A. Kumar, A. Roy, H. Sohlbach, M. Bai, L. Bianchi, M. Büscher, L. Cao, A. Cebulla, R. Dosdall, A. Gillitzer, F. Goldenbaum, D. Grunwald, A. Herten, Q. Hu, G. Kemmerling, H. Kleines, A. Lehrach, R. Nellen, H. Ohm, S. Orfanitski, D. Prasuhn, E. Prencipe, J. Pütz, J. Ritman, S. Schadmand, T. Sefzick, V. Serdyuk, G. Sterzenbach, T. Stockmanns, P. Wintz, P. Wüstner, H. Xu, A. Zambanini, S. Li, Z. Li, Z. Sun, V. Rigato, L. Isaksson, P. Achenbach, O. Corell, A. Denig, M. Distler, M. Hoek, A. Karavdina, W. Lauth, H. Merkel, U. Müller, J. Pochodzalla, S. Schlimme, C. Sfienti, M. Thiel, H. Ahmadi, S. Ahmed, S. Bleser, L. Capozza, M. Cardinali, A. Dbeyssi, M. Deiseroth, F. Feldbauer, M. Fritsch, B. Fröhlich, P. Jasinski, D. Kang, D. Khaneft, R. Klasen, H.H. Leithoff, D. Lin, F. Maas, S. Maldaner, M. Martìnez Rojo, M. Marta, M. Michel, M.C. Mora Espì, C. Morales Morales, C. Motzko, F. Nerling, O. Noll, S. Pflüger, A. Pitka, D. Rodríguez Piñeiro, A. Sanchez Lorente, M. Steinen, R. Valente, T. Weber, M. Zambrana, I. Zimmermann, A. Fedorov, M. Korjik, O. Missevitch, A. Boukharov, O. Malyshev, I. Marishev, P. Balanutsa, V. Balanutsa, V. Chernetsky, A. Demekhin, A. Dolgolenko, P. Fedorets, A. Gerasimov, V. Goryachev, V. Chandratre, V. Datar, D. Dutta, V. Jha, H. Kumawat, A.K. Mohanty, A. Parmar, B. Roy, G. Sonika, C. Fritzsch, S. Grieser, A.K. Hergemöller, B. Hetz, N. Hüsken, A. Khoukaz, J.P. Wessels, K. Khosonthongkee, C. Kobdaj, A. Limphirat, P. Srisawad, Y. Yan, M. Barnyakov, A.Yu. Barnyakov, K. Beloborodov, A.E. Blinov, V.E. Blinov, V.S. Bobrovnikov, S. Kononov, E.A. Kravchenko, I.A. Kuyanov, K. Martin, A.P. Onuchin, S. Serednyakov, A. Sokolov, Y. Tikhonov, E. Atomssa, R. Kunne, D. Marchand, B. Ramstein, J. Van de Wiele, Y. Wang, G. Boca, S. Costanza, P. Genova, P. Montagna, A. Rotondi, V. Abramov, N. Belikov, S. Bukreeva, A. Davidenko, A. Derevschikov, Y. Goncharenko, V. Grishin, V. Kachanov, V. Kormilitsin, A. Levin, Y. Melnik, N. Minaev, V. Mochalov, D. Morozov, L. Nogach, S. Poslavskiy, A. Ryazantsev, S. Ryzhikov, P. Semenov, I. Shein, A. Uzunian, A. Vasiliev, A. Yakutin, E. Tomasi-Gustafsson, U. Roy, B. Yabsley, S. Belostotski, G. Gavrilov, A. Izotov, S. Manaenkov, O. Miklukho, D. Veretennikov, A. Zhdanov, K. Makonyi, M. Preston, P. Tegner, D. Wölbing, T. Bäck, B. Cederwall, A.K. Rai, S. Godre, D. Calvo, S. Coli, P. De Remigis, A. Filippi, G. Giraudo, S. Lusso, G. Mazza, M. Mignone, A. Rivetti, R. Wheadon, F. Balestra, F. Iazzi, R. Introzzi, A. Lavagno, J. Olave, A. Amoroso, M.P. Bussa, L. Busso, F. De Mori, M. Destefanis, L. Fava, L. Ferrero, M. Greco, J. Hu, L. Lavezzi, M. Maggiora, G. Maniscalco, S. Marcello, S. Sosio, S. Spataro, R. Birsa, F. Bradamante, A. Bressan, A. Martin, H. Calen, W. Ikegami Andersson, T. Johansson, A. Kupsc, P. Marciniewski, M. Papenbrock, J. Pettersson, K. Schönning, M. Wolke, B. Galnander, J. Diaz, V. Pothodi Chackara, A. Chlopik, G. Kesik, D. Melnychuk, B. Slowinski, A. Trzcinski, M. Wojciechowski, S. Wronka, B. Zwieglinski, P. Bühler, J. Marton, D. Steinschaden, K. Suzuki, E. Widmann, J. Zmeskal, Jürgen Gerl, Ivan Kojouharov, Jasmina Kojouharova, and Research unit Nuclear & Hadron Physics

Subjects
Particle physics, Nuclear and High Energy Physics, COLLISIONS, Strong interaction, Nuclear Theory, hyperatoms, Antiprotons, Hyperatoms, Hypernuclei, Strangeness, EXCHANGE CURRENTS, 01 natural sciences, Partícules (Física nuclear), NO, Nuclear physics, Subatomär fysik, Hypemuclei, strangeness, DECUPLET BARYONS, ELECTRIC QUADRUPOLE-MOMENTS, 0103 physical sciences, Subatomic Physics, 010306 general physics, Nuclear Experiment, Physics, hypernuclei, NUCLEI, 010308 nuclear & particles physics, Hyperon, Transport theory, DOUBLE-LAMBDA-HYPERNUCLEI, MODEL, OMEGA, Antiproton, Physics::Accelerator Physics, Heavy ion, High Energy Physics::Experiment, antiprotons, INTERMEDIATE ENERGIES, EMULSION
Abstract

Bound nuclear systems with two units of strangeness are still poorly known despite their importance for many strong interaction phenomena. Stored antiprotons beams in the GeV range represent an unparalleled factory for various hyperon-antihyperon pairs. Their outstanding large production probability in antiproton collisions will open the floodgates for a series of new studies of systems which contain two or even more units of strangeness at the PANDA experiment at FAIR. For the first time, high resolution gamma-spectroscopy of doubly strange Lambda Lambda-hypernuclei will be performed, thus complementing measurements of ground state decays of Lambda Lambda-hypernuclei at J-PARC or possible decays of particle unstable hypernuclei in heavy ion reactions. High resolution spectroscopy of multistrange Xi(-) -atoms will be feasible and even the production of Omega(-) -atoms will be within reach. The latter might open the door to the vertical bar S vertical bar = 3 world in strangeness nuclear physics, by the study of the hadronic Omega(-) -nucleus interaction. For the first time it will be possible to study the behavior of Xi(+) in nuclear systems under well controlled conditions. (C) 2016 Elsevier B.V. All rights reserved.

Published
2016
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41. Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation

Author

Bram G. Sengers, N Panitchob, Jocelyn D. Glazier, Colin P. Sibley, Edward D. Johnstone, Ian P. Crocker, Susanne Brooks, Kate Widdows, Rohan M. Lewis, Simone Perazzolo, and Emma M. Lofthouse

Subjects
0301 basic medicine, medicine.medical_specialty, Physiology, Phenylalanine, Placenta, Phenylalanine transport, exchanger, Models, Biological, 03 medical and health sciences, Pregnancy, Physiology (medical), Internal medicine, Journal Article, medicine, blood flow, Humans, facilitated transport, Carbon Radioisotopes, amino acid transfer, Maternal-Fetal Exchange, chemistry.chemical_classification, Fetus, Hormones, Reproduction and Development, business.industry, Biological Transport, Transporter, Metabolism, Amino acid, Perfusion, 030104 developmental biology, Fetal circulation, medicine.anatomical_structure, Endocrinology, Biochemistry, chemistry, Creatinine, Female, business, metabolism
Abstract

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [14C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer.

Published
2016
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42. Technical design report for the $\overline{{\rm{P}}}\mathrm{ANDA}$ Barrel DIRC detector

Author

B Singh, W Erni, B Krusche, M Steinacher, N Walford, B Liu, H Liu, Z Liu, X Shen, C Wang, J Zhao, M Albrecht, T Erlen, F Feldbauer, M Fink, M Fritsch, J Haase, F H Heinsius, T Held, T Holtmann, I Keshk, H Koch, B Kopf, M Kuhlmann, M Kümmel, S Leiber, M Mikirtychyants, P Musiol, A Mustafa, M Pelizäus, A Pitka, J Pychy, M Richter, C Schnier, T Schröder, C Sowa, M Steinke, T Triffterer, U Wiedner, M Ball, R Beck, C Hammann, B Ketzer, M Kube, P Mahlberg, M Rossbach, C Schmidt, R Schmitz, U Thoma, M Urban, D Walther, C Wendel, A Wilson, A Bianconi, M Bragadireanu, D Pantea, B Patel, W Czyzycki, M Domagala, G Filo, J Jaworowski, M Krawczyk, E Lisowski, F Lisowski, M Michałek, P Poznański, J Płażek, K Korcyl, A Kozela, P Kulessa, P Lebiedowicz, K Pysz, W Schäfer, A Szczurek, T Fiutowski, M Idzik, B Mindur, K Swientek, J Biernat, B Kamys, S Kistryn, G Korcyl, W Krzemien, A Magiera, P Moskal, A Pyszniak, Z Rudy, P Salabura, J Smyrski, P Strzempek, A Wronska, I Augustin, R Böhm, I Lehmann, D Nicmorus Marinescu, L Schmitt, V Varentsov, A Ali, M Al-Turany, A Belias, H Deppe, N Divani Veis, R Dzhygadlo, H Flemming, A Gerhardt, K Götzen, A Gromliuk, L Gruber, R Hohler, G Kalicy, R Karabowicz, R Kliemt, M Krebs, U Kurilla, D Lehmann, S Löchner, J Lühning, U Lynen, F Nerling, H Orth, M Patsyuk, K Peters, T Saito, G Schepers, C J Schmidt, C Schwarz, J Schwiening, A Täschner, M Traxler, C Ugur, B Voss, P Wieczorek, A Wilms, M Zühlsdorf, V Abazov, G Alexeev, V A Arefiev, V Astakhov, M Yu Barabanov, B V Batyunya, Y Davydov, V Kh Dodokhov, A Efremov, A Fechtchenko, A G Fedunov, A Galoyan, S Grigoryan, E K Koshurnikov, Y Yu Lobanov, V I Lobanov, A F Makarov, L V Malinina, V Malyshev, A G Olshevskiy, E Perevalova, A A Piskun, T Pocheptsov, G Pontecorvo, V Rodionov, Y Rogov, R Salmin, A Samartsev, M G Sapozhnikov, G Shabratova, N B Skachkov, A N Skachkova, E A Strokovsky, M Suleimanov, R Teshev, V Tokmenin, V Uzhinsky, A Vodopianov, S A Zaporozhets, N I Zhuravlev, A Zinchenko, D Branford, D Glazier, D Watts, M Böhm, A Britting, W Eyrich, A Lehmann, M Pfaffinger, F Uhlig, S Dobbs, K Seth, A Tomaradze, T Xiao, D Bettoni, V Carassiti, A Cotta Ramusino, P Dalpiaz, A Drago, E Fioravanti, I Garzia, M Savrie, V Akishina, S Gorbunov, I Kisel, G Kozlov, M Pugach, M Zyzak, P Gianotti, C Guaraldo, V Lucherini, A Bersani, G Bracco, M Macri, R F Parodi, K Biguenko, K T Brinkmann, V Di Pietro, S Diehl, V Dormenev, M Düren, E Etzelmüller, K Föhl, M Galuska, E Gutz, C Hahn, A Hayrapetyan, M Kesselkaul, K Kreutzfeldt, W Kühn, T Kuske, J S Lange, Y Liang, V Metag, M Moritz, M Nanova, R Novotny, T Quagli, S Reiter, A Riccardi, J Rieke, C Rosenbaum, M Schmidt, R Schnell, H Stenzel, U Thöring, M N Wagner, T Wasem, B Wohlfahrt, H G Zaunick, E Tomasi-Gustafsson, D Ireland, G Rosner, B Seitz, P N Deepak, A Kulkarni, A Apostolou, M Babai, M Kavatsyuk, P J Lemmens, M Lindemulder, H Loehner, J Messchendorp, P Schakel, H Smit, M Tiemens, J C van der Weele, R Veenstra, S Vejdani, K Dutta, K Kalita, A Kumar, A Roy, H Sohlbach, M Bai, L Bianchi, M Büscher, L Cao, A Cebulla, R Dosdall, A Erven, V Fracassi, A Gillitzer, F Goldenbaum, D Grunwald, A Herten, Q Hu, L Jokhovets, G Kemmerling, H Kleines, A Lai, A Lehrach, R Nellen, H Ohm, S Orfanitski, D Prasuhn, E Prencipe, J Pütz, J Ritman, E Rosenthal, S Schadmand, T Sefzick, V Serdyuk, G Sterzenbach, T Stockmanns, P Wintz, P Wüstner, H Xu, S Li, Z Li, Z Sun, V Rigato, L Isaksson, P Achenbach, A Aycock, O Corell, A Denig, M Distler, M Hoek, A Karavdina, W Lauth, H Merkel, U Müller, J Pochodzalla, S Sanchez, S Schlimme, C Sfienti, M Thiel, H Ahmadi, null S Ahmed, S Bleser, L Capozza, M Cardinali, A Dbeyssi, M Deiseroth, A Ehret, B Fröhlich, D Kang, D Khaneft, R Klasen, H H Leithoff, D Lin, F Maas, S Maldaner, M Martínez, M Michel, M C Mora Espí, C Morales Morales, C Motzko, O Noll, S Pflüger, D Rodríguez Piñeiro, A Sanchez-Lorente, M Steinen, R Valente, M Zambrana, I Zimmermann, A Fedorov, M Korjik, O Missevitch, A Balashoff, A Boukharov, O Malyshev, I Marishev, P Balanutsa, V Balanutsa, V Chernetsky, A Demekhin, A Dolgolenko, P Fedorets, A Gerasimov, V Goryachev, V Chandratre, V Datar, D Dutta, V Jha, H Kumawat, A K Mohanty, A Parmar, A K Rai, B Roy, G Sonika, C Fritzsch, S Grieser, A K Hergemöller, B Hetz, N Hüsken, A Khoukaz, J P Wessels, K Khosonthongkee, C Kobdaj, A Limphirat, P Srisawad, Y Yan, E Antokhin, A Yu Barnyakov, M Barnyakov, K Beloborodov, V E Blinov, V S Bobrovnikov, I A Kuyanov, K Martin, A P Onuchin, S Pivovarov, E Pyata, S Serednyakov, A Sokolov, Y Tikhonov, A E Blinov, S Kononov, E A Kravchenko, E Atomssa, R Kunne, D Marchand, B Ramstein, J van de Wiele, Y Wang, G Boca, S Costanza, P Genova, P Montagna, A Rotondi, M Bodlak, M Finger, A Nikolovova, M Pesek, M Peskova, M Pfeffer, I Prochazka, M Slunecka, P Gallus, V Jary, J Novy, M Tomasek, M Virius, V Vrba, V Abramov, N Belikov, S Bukreeva, A Davidenko, A Derevschikov, Y Goncharenko, V Grishin, V Kachanov, V Kormilitsin, A Levin, Y Melnik, N Minaev, V Mochalov, D Morozov, L Nogach, S Poslavskiy, A Ryazantsev, S Ryzhikov, P Semenov, I Shein, A Uzunian, A Vasiliev, A Yakutin, U Roy, B Yabsley, S Belostotski, G Gavrilov, A Izotov, S Manaenkov, O Miklukho, D Veretennikov, A Zhdanov, K Makonyi, M Preston, P E Tegner, D Wölbing, T Bäck, B Cederwall, S Godre, F Balestra, F Iazzi, R Introzzi, A Lavagno, J Olave, A Amoroso, M P Bussa, L Busso, M Destefanis, L Fava, L Ferrero, M Greco, J Hu, L Lavezzi, M Maggiora, G Maniscalco, S Marcello, S Sosio, S Spataro, D Calvo, S Coli, P De Remigis, A Filippi, G Giraudo, S Lusso, G Mazza, M Mignone, A Rivetti, R Wheadon, R Birsa, F Bradamante, A Bressan, A Martin, H Calen, W Ikegami Andersson, T Johansson, A Kupsc, P Marciniewski, M Papenbrock, J Pettersson, K Schönning, M Wolke, B Galnander, J Diaz, V Pothodi Chackara, A Chlopik, G Kesik, D Melnychuk, B Slowinski, A Trzcinski, M Wojciechowski, S Wronka, B Zwieglinski, P Bühler, J Marton, D Steinschaden, K Suzuki, E Widmann, S Zimmermann, and J Zmeskal

Subjects
Physics, Nuclear and High Energy Physics, Range (particle radiation), Large Hadron Collider, Physics::Instrumentation and Detectors, 010308 nuclear & particles physics, Hadron, Detector, Barrel (horology), 7. Clean energy, 01 natural sciences, Ring-imaging Cherenkov detector, Particle identification, Charged particle, Nuclear physics, 0103 physical sciences, High Energy Physics::Experiment, ddc:530, 010306 general physics, Nuclear Experiment
Abstract

The $\overline{{\rm{P}}}\mathrm{ANDA}$ (anti-Proton ANnihiliation at DArmstadt) experiment will be one of the four flagship experiments at the new international accelerator complex FAIR (Facility for Antiproton and Ion Research) in Darmstadt, Germany. $\overline{{\rm{P}}}\mathrm{ANDA}$ will address fundamental questions of hadron physics and quantum chromodynamics using high-intensity cooled antiproton beams with momenta between 1.5 and 15 GeV/c and a design luminosity of up to 2 × 1032 cm−2 s−1. Excellent particle identification (PID) is crucial to the success of the $\overline{{\rm{P}}}\mathrm{ANDA}$ physics program. Hadronic PID in the barrel region of the target spectrometer will be performed by a fast and compact Cherenkov counter using the detection of internally reflected Cherenkov light (DIRC) technology. It is designed to cover the polar angle range from 22° to 140° and will provide at least 3 standard deviations (s.d.) π/K separation up to 3.5 GeV/c, matching the expected upper limit of the final state kaon momentum distribution from simulation. This documents describes the technical design and the expected performance of the $\overline{{\rm{P}}}\mathrm{ANDA}$ Barrel DIRC detector. The design is based on the successful BaBar DIRC with several key improvements. The performance and system cost were optimized in detailed detector simulations and validated with full system prototypes using particle beams at GSI and CERN. The final design meets or exceeds the PID goal of clean π/K separation with at least 3 s.d. over the entire phase space of charged kaons in the Barrel DIRC.

Published
2019
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45. Urotensin II in the development and progression of chronic kidney disease following ⅚ nephrectomy in the rat

Author

Heather J, Eyre, Thomas, Speight, Jocelyn D, Glazier, David M, Smith, and Nick, Ashton

Subjects
Male, Urotensins, Blood Pressure, urologic and male genital diseases, Kidney, urotensin II, Nephrectomy, Research Papers, Rats, Rats, Sprague-Dawley, subtotal nephrectomy, Disease Progression, Animals, Renal Insufficiency, Chronic, Renal, chronic kidney disease, Glomerular Filtration Rate, Research Paper
Abstract

New Findings What is the central question of this study? Urotensin II is upregulated in patients in the later stages of chronic kidney disease (CKD), particularly in individuals requiring dialysis. Could treatment with a urotensin II receptor antagonist slow progression of renal disease? What is the main finding and its importance? In the rat, expression of urotensin II and its receptor increased, extending into cortical structures as CKD progressed towards end‐stage renal failure. Subchronic treatment with a urotensin receptor antagonist slowed but did not prevent progression of CKD. This suggests that urotensin II contributes to the decline in renal function in CKD. Abstract Elevated serum and urine urotensin II (UII) concentrations have been reported in patients with end‐stage chronic kidney disease (CKD). Similar increases in UII and its receptor, UT, have been reported in animal models of CKD, but only at much earlier stages of renal dysfunction. The aim of this study was to characterize urotensin system expression as renal disease progresses to end‐stage failure in a ⅚ subtotal nephrectomy (SNx) rat model. Male Sprague–Dawley rats underwent SNx or sham surgery and were killed at 8 weeks postsurgery [early (E)] or immediately before end‐stage renal failure [30 ± 3 weeks postsurgery; late (L)]. Systolic blood pressure, urinary albumin:creatinine ratio and glomerulosclerosis index were all increased in SNx‐E rats compared with sham‐E by 8 weeks postsurgery. These changes were associated with an increase in renal immunoreactive UII staining but little change in UT expression. As CKD progressed to end‐stage disease in the SNx‐L group, markers of renal function deteriorated further, in association with a marked increase in immunoreactive UII and UT staining. Subchronic administration of a UT antagonist, SB‐611812, at 30 mg kg−1 day−1 for 13 weeks, in a separate group of SNx rats resulted in a 2 week delay in the increase in both systolic blood pressure and urinary albumin:creatinine ratio observed in vehicle‐treated SNx but did not prevent the progression of renal dysfunction. The urotensin system is upregulated as renal function deteriorates in the rat; UT antagonism can slow but not prevent disease progression, suggesting that UII plays a role in CKD.

Published
2018

46. Equilibrative Nucleoside Transporter 1 (ENT1

Author

Lukas, Cerveny, Zuzana, Ptackova, Martina, Ceckova, Rona, Karahoda, Sara, Karbanova, Lucie, Jiraskova, Susan L, Greenwood, Jocelyn D, Glazier, and Frantisek, Staud

Subjects
Adenosine, Anti-HIV Agents, Placenta, Membrane Transport Proteins, Biological Transport, Nucleosides, Nucleoside Transport Proteins, Dideoxynucleosides, Rats, Equilibrative Nucleoside Transporter 1, Pregnancy, Cell Line, Tumor, Animals, Humans, Female, Equilibrative-Nucleoside Transporter 2, Rats, Wistar
Abstract

Abacavir is a preferred antiretroviral drug for preventing mother-to-child human immunodeficiency virus transmission; however, mechanisms of its placental transfer have not been satisfactorily described to date. Because abacavir is a nucleoside-derived drug, we hypothesized that the nucleoside transporters, equilibrative nucleoside transporters (ENTs

Published
2018

47. Relation of placental alkaline phosphatase expression in human term placental to maternal and offspring fat mass

Author

Nicholas C. Harvey, Hazel Inskip, Gernot Desoye, Nina Matthews, Eva Kitzinger, Ingeborg Klymiuk, Keith M. Godfrey, Rohan M. Lewis, Christian Wadsack, Colin P. Sibley, Sarah Crozier, Cyrus Cooper, Birgit Hirschmugl, and Jocelyn D. Glazier

Subjects
Adult, medicine.medical_specialty, Term Birth, Offspring, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, Biology, GPI-Linked Proteins, Article, Cohort Studies, 03 medical and health sciences, Child Development, 0302 clinical medicine, Syncytiotrophoblast, Pregnancy, Internal medicine, Placenta, Gene expression, medicine, Humans, Obesity, Fetus, 030219 obstetrics & reproductive medicine, Nutrition and Dietetics, Symporters, Tumor Suppressor Proteins, Infant, Newborn, Biological Transport, Alkaline Phosphatase, Isoenzymes, Endocrinology, medicine.anatomical_structure, Placental alkaline phosphatase, Prenatal Exposure Delayed Effects, Body Composition, Alkaline phosphatase, Female, Body mass index
Abstract

Alkaline phosphatase is implicated in intestinal lipid transport and in the development of obesity. Placental alkaline phosphatase is localised to the microvillous plasma membrane of the placental syncytiotrophoblast at the maternal–fetal interface, but its role is unclear. We investigated the relations of placental alkaline phosphatase activity and mRNA expression with maternal body composition and offspring fat mass in humans. Term human placentas from the UK Birthright cohort (n = 52) and the Southampton Women’s Survey (SWS) (n = 95) were studied. In the Birthright cohort, alkaline phosphatase activity was measured in placental microvillous plasma membrane vesicles. In the SWS, alkaline phosphatase mRNA was measured using Nanostring. Alkaline phosphatase gene expression was compared to other lipid-related genes. In Birthright samples placental microvillous plasma membrane alkaline phosphatase activity was positively associated with maternal triceps skinfold thickness and BMI (β = 0.04 (95% CI: 0.01–0.06) and β = 0.02 (0.00–0.03) µmol/mg protein/min per SD, P = 0.002 and P = 0.05, respectively) after adjusting for potential confounders. In SWS samples placental alkaline phosphatase mRNA expression in term placenta was positively associated with maternal triceps skinfold (β = 0.24 (0.04, 0.44) SD/SD, P = 0.02), had no association with neonatal %fat mass (β = 0.01 (−0.20 to 0.21) SD/SD, P = 0.93) and was negatively correlated with %fat mass at ages 4 (β = −0.28 (−0.52 to −0.04) SD/SD, P = 0.02), 6–7 (β = −0.25 (−0.49 to −0.02) SD/SD, P = 0.03) years. When compared with placental expression of other genes, alkaline phosphatase expression was positively related to genes including the lysophosphatidylcholine transporter MFSD2A (major facilitator superfamily domain containing 2A, P

Published
2018
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48. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

Author

Colin P. Please, Bram G. Sengers, Colin P. Sibley, Edward D. Johnstone, Ian P. Crocker, Kate Widdows, Rohan M. Lewis, N Panitchob, Jocelyn D. Glazier, and Mark A. Hanson

Subjects
Amino Acid Transport System y+, Placenta, Blotting, Western, Fluorescent Antibody Technique, Large Neutral Amino Acid-Transporter 1, Biology, Models, Biological, Biochemistry, antiporters, Cell membrane, Research Communication, Pregnancy, Serine, Genetics, medicine, Humans, Computer Simulation, Carbon Radioisotopes, facilitated transport, Amino acid transporter, Amino Acids, Transport Vesicles, Molecular Biology, chemistry.chemical_classification, Microvilli, Facilitated diffusion, Fusion Regulatory Protein 1, Light Chains, Vesicle, Cell Membrane, Biological Transport, Membrane transport, Amino acid, Vesicular transport protein, medicine.anatomical_structure, chemistry, overshoot phenomena, Female, LAT2 (SLC7A8), Biotechnology
Abstract

Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanism(s) mediating [14C]L-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that L-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]L-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with L-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms.

Published
2015
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49. Equilibrative nucleoside transporter 1 (ENT1, SLC29A1) facilitates transfer of the antiretroviral drug abacavir across the placenta

Author

Jocelyn D. Glazier, Lukas Cerveny, Rona Karahoda, Susan L. Greenwood, Martina Ceckova, Lucie Jirásková, Sara Karbanova, Frantisek Staud, and Zuzana Ptackova

Subjects
0301 basic medicine, Pharmacology, biology, Chemistry, Pharmaceutical Science, Transporter, Equilibrative nucleoside transporter 2, Apical membrane, Equilibrative nucleoside transporter 1, 030226 pharmacology & pharmacy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Syncytiotrophoblast, Abacavir, Placenta, embryonic structures, biology.protein, medicine, Nucleoside, medicine.drug
Abstract

Abacavir is a preferred antiretroviral drug for preventing mother-to-child human immunodeficiency virus transmission; however, mechanisms of its placental transfer have not been satisfactorily described to date. Because abacavir is a nucleoside-derived drug, we hypothesized that the nucleoside transporters, equilibrative nucleoside transporters (ENTs, SLC29A) and/or Na+-dependent concentrative nucleoside transporters (CNTs, SLC28A), may play a role in its passage across the placenta. To test this hypothesis, we performed uptake experiments using the choriocarcinoma-derived BeWo cell line, human fresh villous fragments, and microvillous plasma membrane (MVM) vesicles. Using endogenous substrates of nucleoside transporters, [3H]-adenosine (ENTs, CNT2, and CNT3) and [3H]-thymidine (ENTs, CNT1, and CNT3), we showed significant activity of ENT1 and CNT2 in BeWo cells, whereas experiments in the villous fragments and MVM vesicles, representing a model of the apical membrane of a syncytiotrophoblast, revealed only ENT1 activity. When testing [3H]-abacavir uptakes, we showed that of the nucleoside transporters, ENT1 plays the dominant role in abacavir uptake into placental tissues, whereas contribution of Na+-dependent transport, most likely mediated by CNTs, was observed only in BeWo cells. Subsequent experiments with dually perfused rat term placentas showed that Ent1 contributes significantly to overall [3H]-abacavir placental transport. Finally, we quantified the expression of SLC29A in first- and third-trimester placentas, revealing that SLC29A1 is the dominant isoform. Neither SLC29A1 nor SLC29A2 expression changed over the course of placental development, but there was considerable interindividual variability in their expression. Therefore, drug-drug interactions and the effect of interindividual variability in placental ENT1 expression on abacavir disposition into fetal circulation should be further investigated to guarantee safe and effective abacavir-based combination therapies in pregnancy.

Published
2018
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50. Computational modelling of amino acid exchange and facilitated transport in placental membrane vesicles

Author

Kate Widdows, C.P. Sibley, N Panitchob, Jocelyn D. Glazier, Rohan M. Lewis, Mark A. Hanson, Edward D. Johnstone, Colin P. Please, Ian P. Crocker, and Bram G. Sengers

Subjects
Statistics and Probability, Time Factors, Placenta, Antiporter, Biology, Models, Biological, Article, Facilitated Diffusion, General Biochemistry, Genetics and Molecular Biology, Placental Membrane, Serine, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Modelling and Simulation, Immunology and Microbiology(all), Humans, Carrier model, Transport Vesicles, Maternal-Fetal Exchange, 030304 developmental biology, Medicine(all), chemistry.chemical_classification, Membrane transport, 0303 health sciences, Membranes, Agricultural and Biological Sciences(all), General Immunology and Microbiology, Facilitated diffusion, Biochemistry, Genetics and Molecular Biology(all), Membrane transport protein, Applied Mathematics, Vesicle, General Medicine, Amino acid, Kinetics, chemistry, Biochemistry, Antiport, Modeling and Simulation, biology.protein, Biophysics, Amino acids, Female, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery
Abstract

Placental amino acid transport is required for fetal development and impaired transport has been associated with poor fetal growth. It is well known that placental amino acid transport is mediated by a broad array of specific membrane transporters with overlapping substrate specificity. However, it is not fully understood how these transporters function, both individually and as an integrated system. We propose that mathematical modelling could help in further elucidating the underlying mechanisms of how these transporters mediate placental amino acid transport. The aim of this work is to model the sodium independent transport of serine, which has been assumed to follow an obligatory exchange mechanism. However, previous amino acid uptake experiments in human placental microvillous plasma membrane vesicles have persistently produced results that are seemingly incompatible with such a mechanism; i.e. transport has been observed under zero-trans conditions, in the absence of internal substrates inside the vesicles to drive exchange. This observation raises two alternative hypotheses; (i) either exchange is not fully obligatory, or (ii) exchange is indeed obligatory, but an unforeseen initial concentration of amino acid substrate is present within the vesicle which could drive exchange. To investigate these possibilities, a mathematical model for tracer uptake was developed based on carrier mediated transport, which can represent either facilitated diffusion or obligatory exchange (also referred to as uniport and antiport mechanisms, respectively). In vitro measurements of serine uptake by placental microvillous membrane vesicles were carried out and the model applied to interpret the results based on the measured apparent Michaelis–Menten parameters Km and Vmax. In addition, based on model predictions, a new time series experiment was implemented to distinguish the hypothesised transporter mechanisms. Analysis of the results indicated the presence of a facilitated transport component, while based on the model no evidence for substantial levels of endogenous amino acids within the vesicle was found., Highlights • Initial rate and time course data for serine uptake in placental membrane vesicles. • Integrated model analysisof facilitative diffusion vs obligatory exchange. • Dependency apparent Michaelis–Menten constants on internal concentrations. • Uptake in placental vesicles was consistent with a facilitative transport component. • No effects of any internal endogenous substrate in vesicles were apparent.

Published
2015
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