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A new experimental setup combining X-ray photon correlation spectroscopy (XPCS) in the hard X-ray regime and a high-pressure sample environment has been developed to monitor the pressure dependence of the internal motion of complex systems down to the atomic scale in the multi-gigapascal range, from room temperature to 600 K. The high flux of coherent high-energy X-rays at fourth-generation synchrotron sources solves the problems caused by the absorption of diamond anvil cells used to generate high pressure, enabling the measurement of the intermediate scattering function over six orders of magnitude in time, from 10-3 s to 10³ s. The constraints posed by the high-pressure generation such as the preservation of X-ray coherence, as well as the sample, pressure and temperature stability, are discussed, and the feasibility of high-pressure XPCS is demonstrated through results obtained on metallic glasses. [ABSTRACT FROM AUTHOR]

Polaritonic chemistry is an interdisciplinary emerging field that presents several challenges and opportunities in chemistry, physics, and engineering. A systematic review of polaritonic response theory is presented, following a chemical perspective based on molecular response theory. We provide the reader with a general strategy for developing response theory for ab initio cavity quantum electrodynamics (QED) methods and critically emphasize details that still need clarification and require cooperation between the physical and chemistry communities. We show that several well‐established results can be applied to strong coupling light‐matter systems, leading to novel perspectives on the computation of matter and photonic properties. The application of the Pauli–Fierz Hamiltonian to polaritons is discussed, focusing on the effects of describing operators in different mathematical representations. We thoroughly examine the most common approximations employed in ab initio QED, such as the dipole approximation. We introduce the polaritonic response equations for the recently developed ab initio QED Hartree–Fock and QED coupled cluster methods. The discussion focuses on the similarities and differences from standard quantum chemistry methods, providing practical equations for computing the polaritonic properties. This article is categorized under:Electronic Structure Theory > Ab Initio Electronic Structure MethodsTheoretical and Physical Chemistry > SpectroscopySoftware > Quantum Chemistry [ABSTRACT FROM AUTHOR]

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder principally due to mutations in the low-density lipoprotein (LDL)-receptor pathway that causes markedly elevated plasma LDL-cholesterol concentration and premature coronary heart disease (CHD).[1] In addition to elevated LDL-cholesterol levels, there is evidence that alterations in reverse cholesterol transport (RCT) may also contribute to accelerating atherosclerosis in FH.[2] Excess cholesterol in macrophages is eliminated via the process of RCT in which cholesterol from peripheral tissues is transported to the liver for biliary excretion.[3] Cholesterol efflux from macrophages, the first step of RCT, plays a major role in anti-atherogenesis. Total cholesterol, LDL-cholesterol, HDL-cholesterol, apoA-I, apoA-II, apo(a) and Lp(a) concentrations were not significantly altered with -3FA treatment, nor were glucose, insulin concentrations and HOMA score. Whether -3FAs improve RCT in the latter stages by promoting hepatobiliary cholesterol excretion merits further investigation by detailed HDL kinetic and cholesterol balance studies. ABCA1 mediates cellular free cholesterol efflux to lipid-poor apoA-I whereas ABCG5 and SR-BI preferentially promotes the efflux of cellular cholesterol to mature apoA-I and/or apoA-II containing HDL particles. [Extracted from the article]

Summary: The occupational demands of law enforcement increase the risk of poor‐quality sleep, putting officers at risk of adverse physical and mental health. This cross‐sectional study aimed to characterise sleep quality in day workers, 8 and 12 h rotating shift pattern workers. One hundred eighty‐six officers volunteered for the study (37 female, age: 41 ± 7). Sleep quality was assessed using the Pittsburgh sleep quality index, actigraphy and the Leeds sleep evaluation questionnaire. The maximal aerobic capacity (VO2max) was measured on a treadmill via breath‐by‐breath analysis. There was a 70% overall prevalence of poor sleepers based on Pittsburgh sleep quality index scores, where 8 h shifts exhibited the worst prevalence (92%, p = 0.029), however, there was no difference between age, gender, or role. In contrast, 12 h shifts exhibited the poorest short‐term measures, including awakening from sleep (p = 0.039) and behaviour following wakefulness (p = 0.033) from subjective measures, and poorer total sleep time (p = 0.024) and sleep efficiency (p = 0.024) from the actigraphy. High VO2max predicted poorer wake after sleep onset (Rsq = 0.07, p = 0.05) and poorer sleep latency (p = 0.028). There was no relationship between the Pittsburgh sleep quality index scores and any of the short‐term measures. The prevalence of poor sleepers in this cohort was substantially higher than in the general population, regardless of shift pattern. The results obtained from the long‐ and short‐term measures of sleep quality yielded opposing results, where long‐term perceptions favoured the 12 h pattern, but short‐term subjective and objective measures both favoured the 8 h pattern. [ABSTRACT FROM AUTHOR]

Background: Cellular cholesterol efflux is a key step in reverse cholesterol transport that may impact on atherosclerotic cardiovascular risk. The process may be reliant on the availability of apolipoprotein (apo) B‐100‐containing lipoproteins to accept cholesterol from high‐density lipoprotein. Evolocumab and atorvastatin are known to lower plasma apoB‐100‐containing lipoproteins that could impact on cholesterol efflux capacity (CEC). Methods: We conducted a 2‐by‐2 factorial trial of the effects of subcutaneous evolocumab (420 mg every 2 weeks) and atorvastatin (80 mg daily) for 8 weeks on CEC in 81 healthy, normolipidaemic men. The capacity of whole plasma and apoB‐depleted plasma, including ATP‐binding cassette transporter A1 (ABCA1)‐mediated and passive diffusion, to efflux cholesterol, was measured. Results: Evolocumab and atorvastatin independently decreased whole plasma CEC (main effect p <.01 for both). However, there were no significant effects of evolocumab and atorvastatin on apoB‐depleted plasma, ABCA1‐mediated and passive diffusion‐mediated CEC (p >.05 in all). In the three intervention groups combined, the reduction in whole plasma CEC was significantly correlated with the corresponding reduction in plasma apoB‐100 concentration (r =.339, p <.01). In the evolocumab monotherapy group, the reduction in whole plasma CEC was also significantly correlated with the corresponding reduction in plasma lipoprotein(a) concentration (r =.487, p <.05). Conclusions: In normolipidaemic men, evolocumab and atorvastatin decrease the capacity of whole plasma to efflux cellular cholesterol. These effects may be chiefly owing to a fall in the availability of apoB‐100‐containing lipoproteins. Reduction in circulating lipoprotein(a) may also contribute to the decrease in whole plasma cholesterol efflux with evolocumab monotherapy. [ABSTRACT FROM AUTHOR]

The lymphatic vasculature has been widely described and explored for its key functions in fluid homeostasis and in the organization and modulation of the immune response. Besides transporting immune cells, lymphatic vessels play relevant roles in tumor growth and tumor cell dissemination. Cancer cells that have invaded into afferent lymphatics are propagated to tumor‐draining lymph nodes (LNs), which represent an important hub for metastatic cell arrest and growth, immune modulation, and secondary dissemination to distant sites. In recent years many studies have reported new mechanisms by which the lymphatic vasculature affects cancer progression, ranging from induction of lymphangiogenesis to metastatic niche preconditioning or immune modulation. In this review, we provide an up‐to‐date description of lymphatic organization and function in peripheral tissues and in LNs and the changes induced to this system by tumor growth and progression. We will specifically focus on the reported interactions that occur between tumor cells and lymphatic endothelial cells (LECs), as well as on interactions between immune cells and LECs, both in the tumor microenvironment and in tumor‐draining LNs. Moreover, the most recent prognostic and therapeutic implications of lymphatics in cancer will be reported and discussed in light of the new immune‐modulatory roles that have been ascribed to LECs. [ABSTRACT FROM AUTHOR]

Background: COVID‐19 is primarily a respiratory syndrome caused by SARS‐CoV‐2 infection, however, a third of COVID‐19 patients report post‐acute neurological sequelae. A close correlation between COVID‐19 and neurodegenerative diseases poses the question of viral etiology and its effect on pre‐existing disease. In this work, we performed brain transcriptomics to compare gene changes in SARS‐CoV‐infected mice and mouse models of Alzheimer's disease (AD) pathology to investigate the relationship between neuroinflammation, immune response, and associated molecular signature of AD. Method: K18‐hACE2 transgenic mice (6‐8 weeks old) expressing human ACE2 receptor were intranasally infected with SARS‐COV‐2 virus (Ancestral USA/WA1/2020). Mock‐infected mice were used as controls. Animals were euthanized 5‐10 days post‐infection. Brains were harvested, treated for viral deactivation, and processed for mRNA extraction. Brains harvested from an uninfected APP/PS1 mouse model of amyloid pathology (9‐12 mo old) and P301S model of tau pathology (8‐9 mo old) were used for comparison. TopHat was used to align RNA‐Seq using Bowtie mapped to the current reference mouse genome assembly. Cufflinks was used to estimate the abundance of transcripts and test for differential expression and regulation. Result: Assessment of differentially expressed genes (p value <0.05) between SARS‐CoV‐2 infected and uninfected K18‐hACE2 brain samples were compared with RNA from uninfected mouse models of AD. The differentially expressed gene set identified 36 upregulated genes that include disrupted RNA metabolism genes, interferon‐ genes, TNF‐associated genes, ubiquitin‐associated genes, transporters, and enzymes. Downregulation of a single gene Tnfrsf17 that has also been reported in patients with severe Covid‐19 (Table 1) and AD patients was observed. Conclusion: Brain transcriptomic profiling of SARS‐CoV‐2 infected mice revealed gene changes that are consistent with those in AD mouse models of amyloid and tau pathology. Our studies warrant further investigation of viral infections as a causative force of transcriptomic changes that precede neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: The multi‐organ physiological responses to spaceflight stressors resemble aging on Earth. We simulate space environment together with environmental stress, as a model of accelerated aging. Redox dys‐homeostasis was shown to contribute to aging‐related pathologies such as Alzheimer's and Parkinson's. The MCAT transgenic mice (overexpressing human catalase in the mitochondria), have increased life span, delayed age‐related pathology and enhanced hippocampal spatial learning and memory. Method: Our study uses 1‐year old C57BL/6NJ male and female mice that underwent exposure to 0.5 gray of gamma radiation together with social isolation. In order to determine ROS contribution to neuro‐behavioral stress response, we used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro‐behavioral consequences of low dose ionizing radiation and social isolation and whether sex differences will be detected. We have performed multiple behavioral tests which focused on performance, memory, physical stance, and stress, together with plasma and hippocampal neuro‐immune panels. Result: We have detected both sex and radiation/isolation effects; the older females look physically better, are faster and perform better almost in all behavioral tasks compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation and isolation in many cases. Interestingly, many of the neuro‐immune changes caused by radiation and social isolation were mitigated in the MCAT mice. In a plasma multiplex cytokine panel, corticosterone (7‐ and 90‐days post radiation), and hippocampal cytokine and microglial activation at the end of the experiment, we have detected significant changes due to radiation, isolation, sex and genotype in both short and long post radiation period. Our focus is now on applying advanced statistical modeling to correlate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits caused by various environmental stresses. Conclusion: Quenching ROS in older mice partially mitigates neuro‐immune consequences of environmental stresses. Significant sex differences were detected, pointing out the importance of examining both sexes, for better personal medicine. The study points out that anti‐oxydant meassures could help older isolated population. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in patients with atrial fibrillation (AF) or for treatment of deep vein thrombosis, although some concerns about safety and efficacy were raised on the use of these drugs in patients with advanced liver disease (ALD). We want to investigate the association of DOACs use with the bleeding and ischaemic risk. Material and Methods: We performed a systematic review and metanalysis of clinical studies retrieved from PubMed (via MEDLINE) and Cochrane (CENTRAL) databases addressing the impact of DOACs therapy on bleeding events including intracranial haemorrhage (ICH), gastrointestinal and major bleeding. Secondary end points were all‐cause death, ischaemic stroke/systemic embolism (IS/SE) and recurrence/progression of vein thrombosis (rDVT). Results: 12 studies were included in the meta‐analysis: a total of 43 532 patients with ALD or cirrhosis, of whom 27 574 (63.3%) were on treatment with DOACs and 15 958 were in warfarin/low molecular weight heparin. DOACs reduced the incidence of major bleeding by 61% (pooled Hazard Ratio [HR] 0.39, 95% Confidence Interval [CI] 0.21‐0.70), ICH by 52% (HR 0.48, 95% CI 0.40‐0.59), while no difference in the reduction of any and gastrointestinal bleeding were observed. DOACs reduced also rDVT by 82% (HR 0.18, 95%CI 0.06‐0.57), but did not reduce death and IS/SE. No difference was shown according to oesophageal varices and Child Pugh score in the meta‐regression analysis between warfarin/heparin and DOACs performed on each outcome. Conclusions: DOACs are associated with a lower incidence of bleeding and may be an attractive therapeutic option in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Objective: Interleukin 12 receptor beta 1 (IL‐12Rβ1) deficiency is a primary immunodeficiency that exposes affected individuals to an augmented risk of intracellular pathogen‐mediated infections. The paradoxical presence of autoimmune manifestations in immune‐deficient patients has been recognized, but the basis of this phenomenon is unclear, with the role of frequent infections being a possible trigger to break tolerance. Our study aimed to analyze extensively a profile of autoantibodies in a clinically well‐defined case series of patients with IL‐12Rβ1 deficiency. Methods: Eight patients with IL‐12Rβ1 deficiency referred to Children's Medical Center in Tunis, Tunisia, during 1995‐2012 were enrolled in the study. Sixteen age‐ and gender‐matched blood donors served as controls. Serum, liver‐related autoantibodies immunoglobulin (Ig)G, IgM, IgA were tested by ELISA and by standard indirect immunofluorescence on Hep‐2 cells. Results: We found a significant prevalence of liver autoantibodies in the study group. Regarding primary biliary cholangitis (PBC), two of eight patients were positive for MIT3 autoantibodies, both confirmed by immunofluorescence, and one patient was positive for PBC‐specific antinuclear antibodies, sp100. Moreover, two patients had significantly increased gamma‐glutamyltransferase levels and one had IgM levels twice the upper limit of normal. Intriguingly two patients were positive for anti‐actin antibodies; a typical feature of autoimmune hepatitis type 1, along with a significant increase in IgG levels. Conclusions: This is the first report of a serological analysis in patients with an IL‐12Rβ1 deficiency. Despite the difficulty in interpreting the role of the IL‐12, the evidence of liver‐specific autoantibodies confirms the importance its signal in liver autoimmunity. [ABSTRACT FROM AUTHOR]

For many years the one‐size‐fits‐all approach has been the only one available to manage patients affected by primary biliary cholangitis. The introduction of obeticholic acid in 2016 as a second‐line treatment, together with the creation and validation of several biochemically based scores to stratify the risk of progressive disease, has opened up the need to redefine clinical practice by changing the actual paradigm. The precision medicine initiative is a model of patient‐centered health care that aims to improve medicine based on genotypic and molecular characteristics that correlate to specific phenotypic, individual characteristics. In summary, the aim of the precision medicine is to define the right treatment for the right person at the right time. The availability of a second‐line disease‐modifying drug and new molecules in phase 2 or 3 trials makes this an exciting time for the precision medicine initiative in primary biliary cholangitis. In this review we describe the current risk stratification tools and we track a possible path towards the application of precision medicine in clinical daily life. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA)‐based hydrogels are one of the most promising naturally derived biomaterials for tissue engineering applications, as they can play an important role in many key cellular processes. In this study, HA was chemically functionalized with photo‐cross‐linkable motifs by reacting with methacrylic anhydride (MA) to obtain methacrylated hyaluronic acid (MeHA). A range of MA/HA molar ratios was used to obtain different degrees of substitution (DS) ranging from 3.5% to 74.5%, as showed by nuclear magnetic resonance and attenuated total reflection spectroscopy. By fine tuning the DS, the chemical reaction parameters, and the polymer concentration, it was demonstrated the possibility to tailor their mechanical features. Double network (DN) hydrogels were prepared through the synergic use of MeHA and polyethylene glycole diacrylate (PEGDA). To improve the biological properties of DN hydrogels, bioactive solid signals such as hydroxyapatite nanoparticles (HAp) prepared by sol–gel approach were used in combination with DN hydrogels to obtain an advanced composite material with dual function in terms of mechanical and biological support for soft/hard tissue formation. The results highlighted that composite‐DN hydrogels showed a 10‐time increase of the storage modulus, if compared to neat MeHA, and an early alkaline phosphatase expression from human mesenchymal stem cells in basal medium. This work can be considered a first systematic approach for the designing of photo‐cross‐linkable hydrogels, based on a combination of natural/synthetic polymers and HAp, that could be applied in three‐dimensional additive manufacturing techniques such as stereolithography. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3079–3089, 2018. [ABSTRACT FROM AUTHOR]

It is well known that the evaluation of a product from the shelf considers the simultaneous cerebral and emotional evaluation of the different qualities of the product such as its colour, the eventual images shown, and the envelope's texture (hereafter all included in the term "product experience"). However, the measurement of cerebral and emotional reactions during the interaction with food products has not been investigated in depth in specialized literature. (e aim of this paper was to investigate such reactions by the EEG and the autonomic activities, as elicited by the cross-sensory interaction (sight and touch) across several different products. In addition, we investigated whether (i) the brand (Major Brand or Private Label), (ii) the familiarity (Foreign or Local Brand), and (iii) the hedonic value of products (Comfort Food or Daily Food) influenced the reaction of a group of volunteers during their interaction with the products. Results showed statistically significantly higher tendency of cerebral approach (as indexed by EEG frontal alpha asymmetry) in response to comfort food during the visual exploration and the visual and tactile exploration phases. Furthermore, for the same index, a higher tendency of approach has been found toward foreign food products in comparison with local food products during the visual and tactile exploration phase. Finally, the same comparison performed on a different index (EEG frontal theta) showed higher mental effort during the interaction with foreign products during the visual exploration and the visual and tactile exploration phases. Results from the present study could deepen the knowledge on the neurophysiological response to food products characterized by different nature in terms of hedonic value familiarity; moreover, they could have implications for food marketers and finally lead to further study on how people make food choices through the interactions with their commercial envelope. [ABSTRACT FROM AUTHOR]

Since Judah Folkman hypothesized in 1971 that angiogenesis is required for solid tumor growth, numerous studies have been conducted to unravel the angiogenesis process, analyze its role in primary tumor growth, metastasis and angiogenic diseases, and to develop inhibitors of proangiogenic factors. These studies have led in 2004 to the approval of the first antiangiogenic agent (bevacizumab, a humanized antibody targeting vascular endothelial growth factor) for the treatment of patients with metastatic colorectal cancer. This approval launched great expectations for the use of antiangiogenic therapy for malignant diseases. However, these expectations have not been met and, as knowledge of blood vessel formation accumulates, many of the original paradigms no longer hold. Therefore, the regulators and clinical implications of angiogenesis need to be revisited. In this review, we discuss recently identified angiogenesis mediators and pathways, new concepts that have emerged over the past 10 years, tumor resistance and toxicity associated with the use of currently available antiangiogenic treatment and potentially new targets and/or approaches for malignant and nonmalignant neovascular diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Sexual differentiation (SD) during development results in anatomical, metabolic, and physiological differences that involve not only the gonads, but also a variety of other biological structures, such as the brain, determining differences in morphology, behavior, and response in the breeding season. In many reptiles, whose sex is determined by egg incubation temperature, such as the leopard gecko, Eublepharis macularius, embryos incubated at different temperatures clearly differ in the volume of brain nuclei that modulate behavior. Based on the premise that 'the developmental decision of gender does not flow through a single gene', we performed an analysis on E. macularius using three approaches to gain insights into the genes that may be involved in brain SD during the thermosensitive period. Using quantitative RT-PCR, we studied the expression of genes known to be involved in gonadal SD such as WNT4, SOX9, DMRT1, Erα, Erβ, GnRH, P450 aromatase, PRL, and PRL-R. Then, further genes putatively involved in sex dimorphic brain differentiation were sought by differential display (DDRT-PCR) and PCR array. Our findings indicate that embryo exposure to different sex determining temperatures induces differential expression of several genes that are involved not only in gonadal differentiation ( PRL-R, Wnt4, Erα, Erβ, p450 aromatase, and DMRT1), but also in neural differentiation ( TN-R, Adora2A, and ASCL1) and metabolic pathways ( GP1, RPS15, and NADH12). These data suggest that the brains of SDT reptiles might be dimorphic at birth, thus behavioral experiences in postnatal development would act on a structure already committed to male or female. [ABSTRACT FROM AUTHOR]

The polymerization of ethylene to Ultra-High Molecular Weight Polyethylene (UHMWPE) in certain reaction conditions allows synthesis of nascent powders with a considerably lower amount of entanglements: the material obtained is of great interest from both academic and industrial viewpoints. From an academic point of view, it is interesting to follow the evolution of the metastable melt state with the progressive entanglements formation. Industrially, it is valuable to have a solvent-free processing route for the production of high modulus, high strength tapes. Since the polymer synthesis is performed in the presence of a solvent, it is interesting to investigate the influence that the reaction medium can have on the catalyst activity, resultant molecular characteristics, and polymer morphology at the macroscopic as wells as microscopic level. In this paper, we present the effect that two typical polymerization solvents, toluene and heptane, and mixtures of them, have on the catalytic performance and on the polymer properties. The observations are that an unexpected increase of catalyst activity, accompanied by a significant improvement in mechanical properties, is found when using a carefully chosen mixture of solvents. A tentative explanation is given on the basis of the presented results. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is an organophosphate insecticide used primarily to control foliage and soil-borne insect pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce dose-related abnormalities such as slower brain growth and cerebral cortex thinning. In lower vertebrates, for example, fish and amphibians, teratogenic activity of this compound is correlated with several anatomical alterations. Little is known about the effects of CPF on mRNA expression of genes involved in early development of the anatomical structures appearing abnormal in embryos. This study investigated the effects of exposure to different CPF concentrations (10, 15 and 20 mg/L) on Xenopus laevis embryos from stage 4/8 to stage 46. Some of the morphological changes we detected in CPF-exposed embryos included cranial neural crest cell (NCC)-derived structures. For this reason, we analyzed the expression of select genes involved in hindbrain patterning ( egr2), cranial neural crest chondrogenesis, and craniofacial development ( fgf8, bmp4, sox9, hoxa2 and hoxb2). We found that CPF exposure induced a reduction in transcription of all the genes involved in NCC-dependent chondrogenesis, with largest reductions in fgf8 and sox9; whereas, in hindbrain, we did not find any alterations in egr2 expression. Changes in the expression of fgf8, bmp4, and sox9, which are master regulators of several developmental pathways, have important implications. If these changes are confirmed to belong to a general pattern of alterations in vertebrates prenatally exposed to OP, they might be useful to assess damage during vertebrate embryo development. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The activation of a bis-phenoxyimine catalyst based on titanium (IV) using different aluminoxanes (MAO, PMAO and MMAO12) has been studied. The effect of a co-catalyst modifier (BHT) used in combination with the MAO has been also tested. In particular, the effect of the activation time between the catalyst and the different aluminoxanes has been taken into consideration. On increasing the activation time between catalyst and the different aluminoxanes and TMA-free MAO, differences in the catalyst activities have been observed. UHMWPEs having a reduced number of entanglements have been synthesized activating the FI catalyst with MAO and TMA-free MAO. The obtained reactor powders can be solid-state processed below the melting temperature in order to obtain high modulus/high tenacity tapes used for body armor and vehicle protection applications. [ABSTRACT FROM AUTHOR]

Recently, it has been shown that by using a single-site catalytic system having titanium as a metallic center, it is possible to tailor the entanglement density in the amorphous region of a semi-crystalline ultra-high molecular weight polyethylene (UHMWPE). This route provides the possibility to make high-modulus, high-strength uniaxially and biaxially drawn tapes and films, without using any solvent during processing. In this publication, it is shown that a single-site catalyst having chromium as metallic center, proposed by Enders and co-workers, can also be tuned to provide control on the entanglement density during synthesis of the UHMWPE. However, to achieve the goal some modifications during the synthesis are required. The synthesized polymers can be processed in the solid state below the equilibrium melting temperature, resulting in uniaxially drawn tapes having tensile strength and modulus greater than 3.5 N/tex and 200 N/tex, respectively. Rheological studies have been performed to follow the increase in entanglement density in melt state with time. [ABSTRACT FROM AUTHOR]

N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway with an isopentenyl chain, is already known to exert a suppressor effect against various tumors. In this work, we investigated whether iPA also directly interferes with the angiogenic process, which is fundamental to tumor growth and progression. To this end, using human umbilical vein endothelial cells (HUVECs) as a suitable in vitro model of angiogenesis, we evaluated their viability, proliferation, migration, invasion, tube formation in response to iPA, and molecular mechanisms involved. Data were corroborated in mice by using a gel plug assay, iPA dose- and time-dependently inhibited all the neoangiogenesis stages, with an IC50 of 0.98 µM. We demonstrated for the first time, by liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS), that iPA was monophosphorylated into 5'-iPA-monophosphate (iPAMP) by the adenosine kinase (ADK) inside the cells, iPAMP is the active form that inhibits angiogenesis through the direct activation of AMP-kinase (AMPK). Indeed, all effects were completely reversed by pretreatment with 5-iodotubercidin (5-Itu), an ADK inhibitor. The isoprenoid intermediate isopentenyl pyrophosphate (IPP), which shares the isopentenyl moiety with iPA, was ineffective in the inhibition of anglogenesis, thus showing that the iPA structure is specific for the observed effects. In conclusion, iPA is a novel AMPK activator and could represent a useful tool for the treatment of diseases where excessive neoangiogenesis is the underlying pathology. [ABSTRACT FROM AUTHOR]

This study represents the first longitudinal, within-subject 1H MRS investigation of the developing rat brain spanning infancy, adolescence and early adulthood. We obtained neurometabolite profiles from a voxel located in a central location of the forebrain, centered on the striatum, with smaller contributions for the cortex, thalamus and hypothalamus, on postnatal days 7, 35 and 60. Water-scaled metabolite signals were corrected for T1 effects and quantified using the automated processing software LCModel, yielding molal concentrations. Our findings indicate age-related concentration changes in N-acetylaspartate + N-acetylaspartylglutamate, myo-inositol, glutamate + glutamine, taurine, creatine + phosphocreatine and glycerophosphocholine + phosphocholine. Using a repeated measures design and analysis, we identified significant neurodevelopment changes across all three developmental ages and identified adolescence as a distinctive phase in normative neurometabolic brain development. Between postnatal days 35 and 60, changes were observed in the concentrations of N-acetylaspartate + N-acetylaspartylglutamate, glutamate + glutamine and glycerophosphocholine + phosphocholine. Our data replicate past studies of early neurometabolite development and, for the first time, link maturational profiles in the same subjects across infancy, adolescence and adulthood. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors ( FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone ( DHT) up-regulates FGF2 and FGF8b production in murine TRAMP-C2 prostate cancer cells, activating a FGF-dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin-3 ( PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N-terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3-derived pentapeptide Ac- ARPCA-NH2 abolish the mitogenic response of murine TRAMP-C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT-activated TRAMP-C2 cells on the chick embryo chorioallantoic membrane ( CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP- C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP- C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP-C2 cells overexpress only the FGF-binding N-terminal PTX3 domain. In keeping with the anti-tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high-grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti-angiogenic and anti-neoplastic activity in prostate cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Mouse models with prenatal alterations in dopaminergic functioning can provide new opportunities to identify fetal behavioral abnormalities and the underlying neural substrates dependent on dopamine. In this study, we tested the hypothesis that prenatal loss of nigrostriatal function is associated with fetal akinesia, or difficulty initiating movement. Specific behaviors were analysed in fetal offspring derived from pregnant Pitx3ak/2J and C57BL/6J dams on the last 4 days before birth (E15-18 of a 19-day gestation). Using digital videography, we analysed: (i) behavioral state, by quantification of high- and low-amplitude movements, (ii) interlimb movement synchrony, a measure of the temporal relationship between spontaneous movements of limb pairs, (iii) facial wiping, a characteristic response to perioral tactile stimulation similar to the defensive response in human infants, and (iv) oral grasp of a non-nutritive nipple, a component of suckling in the human infant. Pitx3 mutants showed a selective decrease in interlimb movement synchrony rates at the shortest (0.1 s) temporal interval coupled with significantly increased latencies to exhibit facial wiping and oral grasp. Collectively, our findings provide evidence that the primary fetal neurobehavioral deficit of the Pitx3 mutation is akinesia related to nigrostriatal damage. Other findings of particular interest were the differences in neurobehavioral functioning between C57BL/6J and Pitx3 heterozygous subjects, suggesting the two groups are not equivalent controls. These results further suggest that fetal neurobehavioral assessments are sensitive indicators of emerging neural dysfunction, and may have utility for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

The role of submicroscopic infections in modulating malaria antibody responses is poorly understood and requires longitudinal studies. A cohort of 249 children ≤5 years of age, 126 children between 6 and 10 years and 134 adults ≥20 years was recruited in an area of intense malaria transmission in Apac, Uganda and treated with artemether/lumefantrine at enrolment. Parasite carriage was determined at enrolment and after 6 and 16 weeks using microscopy and PCR. Antibody prevalence and titres to circumsporozoite protein, apical membrane antigen-1 ( AMA-1), merozoite surface protein-1 ( MSP-119), merozoite surface protein-2 ( MSP-2) and Anopheles gambiae salivary gland protein 6 (g SG6) were determined by ELISA. Plasmodium falciparum infections were detected in 38·1% (194/509) of the individuals by microscopy and in 57·1% (284/493) of the individuals by PCR at enrolment. Antibody prevalence and titre against AMA-1, MSP-119, MSP-2 and g SG6 were related to concurrent (sub-)microscopic parasitaemia. Responses were stable in children who were continuously infected with malaria parasites but declined in children who were never parasitaemic during the study or were not re-infected after treatment. These findings indicate that continued malaria infections are required to maintain antibody titres in an area of intense malaria transmission. [ABSTRACT FROM AUTHOR]

The use of a hindered phenol to trap free trimethylaluminum (TMA) in methylaluminoxane (MAO) solutions has been reported to improve the performance of single-site, homogeneous catalysts for olefin polymerization. In the present study, with the help of rheological analyses, we have investigated and compared the molecular weight, molecular weight distribution and entanglement density of ultrahigh molecular weight polyethylene synthesized with a single-site catalyst activated by MAO and phenol-modified MAO. While the number average molecular weight ( Mn) of the obtained polymers remains the same for both activations, a higher yield and a higher entanglement density are found in the initial stages of polymerization on using phenol-modified MAO as the cocatalyst. These results suggest that on using the phenol-modified MAO as activator, a higher number of active sites are obtained. Surprisingly in the presence of untreated MAO, a tail in the higher molecular mass region is produced. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 [ABSTRACT FROM AUTHOR]

Understanding the developmental origins of congenital capabilities such as sucking is fundamental knowledge that can contribute to improving the clinical management of early feeding and facilitate the onset of oral ingestion. We describe analyses in rats showing that sensory stimulation in utero and during birth establishes the newborn's sucking responses to maternal cues. We mimicked elements of labor and delivery (viz., compressions simulating labor contractions, stroking simulating postnatal maternal licking of the newborn, and postnatal thermal flux), and used them to induce postnatal respiration and nipple attachment in caesariandelivered pups. We report herein new data showing that, by simulating a fetal rat's experience of being born, specific components of vaginal birth provide sufficient conditions for the odor learning that guides newborn's sucking responses. In contrast, the absence of in utero compressions was associated with poor sucking onset. Knowing how birth stimuli contribute to the first nipple attachment and constitute a context for learning to suckle is an important step toward better management of some early feeding problems. It can serve also as a foundation for understanding the challenges of facilitating sucking by babies born prematurely so that they do not experience the typical contingencies mediating onset of oral ingestion. [ABSTRACT FROM AUTHOR]

Fibronectin (FN) is an extracellular matrix cell-adhesive glycoprotein. The alternative spliced isoform EDB-FN (extra domain B containing FN) is highly expressed in tumour blood vessels and stroma and represents a candidate for tumour targeting. To investigate the impact of different angiogenic micro-environments on EDB-FN expression, we used a tumour model in which human endometrial adenocarcinoma Tet-FGF2 cells overexpressing fibroblast growth factor-2 (FGF2) driven by the tetracycline-responsive promoter were further transfected with a VEGF antisense cDNA, generating AS-VEGF/Tet-FGF2 cells. In this model, the expression of FGF2 plus VEGF results in fast-growing, highly vascularized Tet-FGF2 tumours. Down-regulation of FGF2 production by tetracycline administration and/or of VEGF production by AS-VEGF transduction inhibited tumour growth and vascularization, with profound changes in tumour micro-environment. Quantitative RT-PCR analysis using human EDB-FN primers shows that subcutaneous grafting in immunodeficient mice is per se sufficient to cause a dramatic up-regulation of EDB-FN expression by these cells, as well as by human oesophageal cancer KYSE 30 cells and renal carcinoma Caki-1 cells. However, in vivo down-regulation of VEGF expression, as occurs in AS-VEGF/Tet-FGF2 tumours, and to a lesser extent of FGF2 expression, as occurs in tetracycline-treated Tet-FGF2 tumour-bearing animals, causes significant inhibition of EDB-FN production in tumour grafts, as shown by immunohistochemistry and quantitative RT-PCR analysis. Accordingly, treatment of Tet-FGF2 tumour-bearing animals with the neutralizing anti-murine VEGF receptor-2 antibody DC101, or of Caki-1 tumour-bearing animals with the anti-VEGF antibody bevacizumab, inhibited EDB-FN expression in tumour grafts. EDB-FN down-regulation was paralleled by a decrease in vascularity, thus confirming EDB-FN as a marker of tumour angiogenesis. These data demonstrate that the angiogenic micro-environment, and in particular the VEGF/VEGFR-2 system, plays a key role in modulating EDB-FN expression by tumour cells in vivo. This may have implications for the design of therapeutic strategies targeting EDB-FN in combination with anti-angiogenic and/or cytotoxic drugs. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

3-iodothyronamine (T1AM) is a novel endogenous relative of thyroid hormone, able to interact with trace amine-associated receptors, a class of plasma membrane G protein-coupled receptors, and to produce a negative inotropic and chronotropic effect. In the isolated rat heart 20–25 μM T1AM decreased cardiac contractility, but oxygen consumption and glucose uptake were either unchanged or disproportionately high when compared to mechanical work. In adult rat cardiomyocytes acute exposure to 20 μM T1AM decreased the amplitude and duration of the calcium transient. In patch clamped cardiomyocytes sarcolemmal calcium current density was unchanged while current facilitation by membrane depolarization was abolished consistent with reduced sarcoplasmic reticulum (SR) calcium release. In addition, T1AM decreased transient outward current ( Ito) and IK1 background current. SR studies involving 20 μM T1AM revealed a significant decrease in ryanodine binding due to reduced Bmax, no significant change in the rate constant of calcium-induced calcium release, a significant increase in calcium leak measured under conditions promoting channel closure, and no effect on oxalate-supported calcium uptake. Based on these observations we conclude T1AM affects calcium and potassium homeostasis and suggest its negative inotropic action is due to a diminished pool of SR calcium as a result of increased diastolic leak through the ryanodine receptor, while increased action potential duration is accounted for by inhibition of Ito and IK1 currents. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor-1 (Fgfr1) gene knockout impairs cardiac and haematopoietic development in murine embryonic stem cells (mESC). In FGFR1, tyrosine residues Y653 and Y654 are responsible for its tyrosine kinase (TK) activity whereas phosphorylated Y463 and Y766 represent docking sites for intracellular substrates. Aim of this study was the characterization of FGFR1 signalling requirements necessary for cardiomyocyte differentiation in mESC. To this purpose, fgfr1−/− mESC were infected with lentiviral vectors harbouring human wild-type hFGFR1 or the Y653/654F, Y463F and Y766F hFGFR1 mutants. The resulting embryonic stem (ES) cell lines were differentiated as embryoid bodies (EBs) and beating foci formation was evaluated. In order to appraise the presence of cells belonging to cardiovascular and haematopoietic lineages, specific markers were analysed by quantitative PCR, whole mount in situ hybridization and immunofluorescence. Transduction with TK+ hFGFR1 or the TK+ Y766F-hFGFR1 mutant rescued cardiomyocyte beating foci formation in fgfr1−/− EBs whereas the TK− Y653/654F-hFGFR1 mutant and the TK+ Y463F-hFGFR1 mutant were both ineffective. Analysis of the expression of early and late cardiac markers in differentiating EBs confirmed these observations. At variance with cardiomyocyte differentiation, all the transduced TK+ FGFR1 forms were able to rescue haematopoietic differentiation in EBs originated by infected fgfr1−/− mESC, only the TK− Y653/654F-hFGFR1 mutant being ineffective. In keeping with these observations, treatment with different signalling pathway inhibitors indicates that protein kinase C and ERK activation are essential for cardiomyocyte but not for haematopoietic differentiation in EBs generated by fgfr1+/−∼ mESC. In conclusion, our results suggest that, although FGFR1 kinase activity is necessary for both cardiac and haematopoietic lineage maturation in mESC, phosphorylation of Y463 in the intracellular domain of the receptor is a specific requirement for cardiomyocyte differentiation. [ABSTRACT FROM AUTHOR]

The study of fetal neurobehavioral development in genetically altered mice promises a significant advance in our understanding of the prenatal origins of developmental disabilities in humans. Despite their importance, little is known about fetal neurobehavioral development in mice. In this study, we observed prenatal behavioral patterns of the C57BL/6J mouse, a common background strain for genetically altered mice, and report their similarity to those observed in the early to mid-gestation human fetus. Fetal offspring from pregnant C57BL/6J dams were observed on the day before birth (E18 of a 19-day gestation). Scoring and analysis of fetal movement included Prechtl's Method for Qualitative Assessment, Interlimb Movement Synchrony, a measure of the temporal relationship between movements of limb pairs, and Behavioral State, quantified through detailed analysis of high and low amplitude limb movements. With the exception of fetal breathing movements, all categories and patterns of behavior typically reported in the early to mid-gestation human fetus were observed in the C57BL/6J mouse fetus. Our results suggest that behavioral analysis of fetal C57BL/6J mice may yield important new insights into early to mid-gestation human behavioral development. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 51: 84–94, 2009 [ABSTRACT FROM AUTHOR]

The article presents a study which prepared and characterized immiscible blends of high molecular weight commercial poly(p-dioxanone) (PPDX) and poly( ε-caprolactone) (PCL). The results showed that the PPDX component in the blends has a much faster degradation rate than in neat PPDX which could be due to the larger surface area of PPDX composites. The study concluded that the blends may be a good option to replace neat PPDX in applications requiring longer life time of the material.

Our understanding of prenatal behavior has been significantly advanced by techniques for direct observation and manipulation of unanesthetized, behaving rodent fetuses with intact umbilical connections to the mother. These techniques involve brief administration of an inhalant anesthesic, enabling spinal transection of the rat or mouse dam, after which procedures can continue with unanesthetized dams and fetuses. Because anesthetics administered to the mother can cross the placental barrier, it is possible that fetuses are anesthetized to varying degrees. We compared in perinatal rats the effects of prenatal maternal exposure to two inhalant anesthetics: ether and isoflurane. Fewer spontaneous fetal movements and first postpartum nipple attachments were observed following maternal exposure to ether as compared to isoflurane. Neonatal breathing frequencies and oxygenation did not account for group differences in nipple attachment. Our results provide evidence that the particular inhalant anesthetic employed in prenatal manipulation studies determines frequencies of perinatal behavior. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 675–684, 2007. [ABSTRACT FROM AUTHOR]

3-iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27±5, 51±3, and 65±2% decrease in cardiac output at 19, 25, and 38 µM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 µM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function. [ABSTRACT FROM AUTHOR]

In polymer composites the interaction between polymer matrix and filler particles often results in nucleation of spherulites. The principles of polymer crystal nucleation and spherulite growth are investigated using scanning transmission electron microscopy (STEM) and microdiffraction techniques in combination with polarized light microscopy. Simultaneous diffraction patterns from the interface of the filler and the polymer were obtained. Special precautions for successful recording of the diffraction patterns were used to overcome the rapid loss of polymer crystallinity, resulting from electron beam damage. Analysis of the diffraction patterns has shown that partial epitaxial correlation between the atomic periodicity of the particle surface and the molecular periodicity of polymer chains is always present when spherulites are nucleated. STEM images show that only large particles, with well developed facets (cleavage planes), are nucleating. The nucleating efficiency of the filler is therefore dependent on the size as well as on the crystallographic orientation of the facet. Small particles, or those with no suitable facets, do not affect the crystalline structure of the polymer. It is also shown that anisotropic polymer structures can be formed by inhomogeneous dispersion of nucleating filler particles. [ABSTRACT FROM AUTHOR]