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Low level expression in Escherichia coli of the RecA protein from the radiation resistant bacterium Deinococcus radiodurans protects a RecA deficient strain of E. coli from UV-A irradiation by up to ∼160% over basal UV-A resistance. The protection effect is inverse protein dose dependent: increasing the expression level of the D. radiodurans RecA (DrRecA) protein decreases the protection factor. This inverse protein dose dependence effect helps resolve previously conflicting reports of whether DrRecA expression is protective or toxic for E. coli. In contrast to the D. radiodurans protein effect, conspecific plasmid expression of E. coli RecA protein in RecA deficient E. coli is consistently protective over several protein expression levels, as well as consistently more protective to higher levels of UV-A exposure than that provided by the D. radiodurans protein. The results indicate that plasmid expression of D. radiodurans RecA can modestly enhance the UV resistance of living E. coli , but that the heterospecific protein shifts from protective to toxic as expression is increased. • Heterospectific expression of D. radiodurans RecA protein in E. coli confers modest organismal protection to UV-A damage. • The D. radiodurans RecA UV-A protection is inverse protein dose dependent: protection occurs at low but not high expression. • Conspecific expression of E. coli RecA protein in E. coli confers consistent but modest UV-A protection at all expression levels. • Conspecific RecA protein is more UV-A protective for E. coli cells than heterospecific D. radiodurans RecA protein. [ABSTRACT FROM AUTHOR]

The topic is the average order of a connected induced subgraph of a graph. This generalizes, to graphs in general, the average order of a subtree of a tree. In 1983, Jamison proved that the average order of a subtree, over all trees of order n , is minimized by the path P n. In 2018, Kroeker, Mol, and Oellermann conjectured that P n minimizes the average order of a connected induced subgraph over all connected graphs. The main result of this paper confirms this conjecture. [ABSTRACT FROM AUTHOR]

Tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTPBE) are both brominated flame retardants (BFRs) that have been detected in birds; however, their potential biological effects are largely unknown. We assessed the effects of embryonic exposure to TBBPA-BDBPE and BTBPE in a model avian predator, the American kestrel (Falco sparverius). Fertile eggs from a captive population of kestrels were injected on embryonic day 5 (ED5) with a vehicle control or one of three doses within the range of concentrations that have been detected in biota (nominal concentrations of 0, 10, 50 or 100 ng/g egg; measured concentrations 0, 3.0, 13.7 or 33.5 ng TBBPA-BDBPE/g egg and 0, 5.3, 26.8 or 58.1 ng BTBPE/g egg). Eggs were artificially incubated until hatching (ED28), at which point blood and tissues were collected to measure morphological and physiological endpoints, including organ somatic indices, circulating and glandular thyroid hormone concentrations, thyroid gland histology, hepatic deiodinase activity, and markers of oxidative stress. Neither compound had any effects on embryo survival through 90% of the incubation period or on hatching success, body mass, organ size, or oxidative stress of hatchlings. There was evidence of sex-specific effects in the thyroid system responses to the BTBPE exposures, with type 2 deiodinase (D2) activity decreasing at higher doses in female, but not in male hatchlings, suggesting that females may be more sensitive to BTBPE. However, there were no effects of TBBPA-BDBPE on the thyroid system in kestrels. For the BTPBE study, a subset of high-dose eggs was collected throughout the incubation period to measure changes in BTBPE concentrations. There was no decrease in BTBPE over the incubation period, suggesting that BTBPE is slowly metabolized by kestrel embryos throughout their ∼28-d development. These two compounds, therefore, do not appear to be particularly toxic to embryos of the American kestrel. • TBBPA-BDBPE and BTBPE are replacement BFR contaminants detected in birds. • We assessed effects of developmental exposure in birds using a model avian predator. • Embryos were exposed to concentrations reflecting those reported in wild bird eggs. • TBBPA-BDBPE did not affect hatching success, morphological or physiological endpoints. • BTBPE suppressed deiodinase enzymes in females, but had no other effects. [ABSTRACT FROM AUTHOR]

The programmed cell death machinery exhibits surprising flexibility, capable of crosstalk and non-apoptotic roles. Much of this complexity arises from the diverse functions of caspase-8, a cysteine-aspartic acid protease typically associated with activating caspase-3 and − 7 to induce apoptosis. However, recent research has revealed that caspase-8 also plays a role in regulating the lytic gasdermin cell death machinery, contributing to pyroptosis and immune responses in contexts such as infection, autoinflammation, and T-cell signalling. In mice, loss of caspase-8 results in embryonic lethality from unrestrained necroptotic killing, while in humans caspase-8 deficiency can lead to an autoimmune lymphoproliferative syndrome, immunodeficiency, inflammatory bowel disease or, when it can't cleave its substrate RIPK1, early onset periodic fevers. This review focuses on non-canonical caspase-8 signalling that drives immune responses, including its regulation of inflammatory gene transcription, activation within inflammasome complexes, and roles in pyroptotic cell death. Ultimately, a deeper understanding of caspase-8 function will aid in determining whether, and when, targeting caspase-8 pathways could be therapeutically beneficial in human diseases. • Dysregulated caspase-8 signalling causes immunodeficiency and inflammatory diseases. • Caspase-8 has both enzymatic and scaffolding functions. • Non-apoptotic caspase-8 gene transcription is critical for immunity. • Caspase-8 can be recruited into inflammasome complexes to cause cell death. • Caspase-8 can cause pyroptosis through GSDMC, GSDMD and GSDME activation. [ABSTRACT FROM AUTHOR]

Abstract Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials. Highlights • Frontotemporal Dementia is preceded by a long period of subtle brain changes. • Time-varying dynamic connectivity can unveiled underappreciated brain details. • Presymptomatic Frontotemporal Dementia exhibits a reduced dynamic fluidity. • Frontotemporal Dementia showed a selective vulnerability of specific brain regions. • At the very early stage Frontotemporal Dementia is affecting brain as global system. [ABSTRACT FROM AUTHOR]

Abstract Temperament consists of multi-dimensional traits that affect various domains of human life. Evidence has shown functional connectome-based predictive models are powerful predictors of cognitive abilities. Putatively, individuals' innate temperament traits may be predictable by unique patterns of brain functional connectivity (FC) as well. However, quantitative prediction for multiple temperament traits at the individual level has not yet been studied. Therefore, we were motivated to realize the individualized prediction of four temperament traits (novelty seeking [NS], harm avoidance [HA], reward dependence [RD] and persistence [PS]) using whole-brain FC. Specifically, a multivariate prediction framework integrating feature selection and sparse regression was applied to resting-state fMRI data from 360 college students, resulting in 4 connectome-based predictive models that enabled prediction of temperament scores for unseen subjects in cross-validation. More importantly, predictive models for HA and NS could be successfully generalized to two relevant personality traits for unseen individuals, i.e. , neuroticism and extraversion, in an independent dataset. In four temperament trait predictions, brain connectivities that show top contributing power commonly concentrated on the hippocampus, prefrontal cortex, basal ganglia, amygdala, and cingulate gyrus. Finally, across independent datasets and multiple traits, we show person's temperament traits can be reliably predicted using functional connectivity strength within frontal-subcortical circuits, indicating that human social and behavioral performance can be characterized by specific brain connectivity profile. Highlights • Development of connectome-based predictive models for four temperament metrics. • Temperaments can be characterized by functional connections within the frontal-subcortical circuits. • Prediction of harm avoidance can be generalized to neuroticism in new independent dataset. • Prediction of novelty seeking can be generalized to extraversion in new independent dataset. [ABSTRACT FROM AUTHOR]

Klenow and Klentaq are the large fragment domains of the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus , respectively. Herein, we show that both polymerases can significantly stimulate complementary intermolecular end-joining ligations by E.coli DNA ligase when the polymerases are present at concentrations lower than that of the DNA substrates. In contrast, high polymerase concentrations relative to the DNA substrates inhibit the intermolecular ligation activity of DNA ligase. Neither polymerase was able to stimulate the DNA ligase from T4 bacteriophage. Additionally, nick-closure by E. coli DNA ligase (but not T4 ligase) is slightly stimulated by both polymerases, but only at about 10% of the magnitude seen for end-joining enhancement. The data represent one of the first observations of direct polymerase-ligase interactions in prokaryotes, and suggest that the polymerases stabilize the associated DNA ends during intermolecular ligation, and that such a complex can be taken advantage of by some, but not all, DNA ligases. [ABSTRACT FROM AUTHOR]

The development of third party assessment and certification of fisheries and aquaculture has provided new forms of governance in sectors that were traditionally dominated by state based regulation. Emerging market based approaches are driven by shareholder expectations as well as commitment to corporate social responsibility, whereas community engagement is increasingly centered on the questions of social license to operate. Third party assessment and certification links state, market and community into an interesting and challenging hybrid form of governance. While civil society organizations have long been active in pursuing sustainable and safe seafood production, the development of formal non-state based certification provides both opportunities and challenges, and opens up interesting debates over hybrid forms of governance. This paper explores these developments in coastal marine resources management, focusing on aquaculture and the development and operation of the Aquaculture Stewardship Council. It examines the case of salmonid aquaculture in Tasmania, Australia, now Australia's most valuable seafood industry, which remains the focus of considerable community debate over its siting, operation and environmental impact. [ABSTRACT FROM AUTHOR]

The diachronic development of the crossbow brooch was examined for northern Gaul during the Late Roman period (3rd to 5th century) in order to extrapolate changes in production organisation from variation in the copper-alloy composition and shape of the artefacts. A combined method of surface analysis by handheld XRF and dimensional analyses by focussing on variation or similarity was applied and interpreted in a typological framework to confirm and enhance the traditional production model of the crossbow brooch. This led to new insights into the processes of regionality and state-control in Roman metal production in a provincial context. From a simple military commodity to an elite symbol of power and authority, these changes in production and consumption reflect sociocultural changes in the Late Roman West. [ABSTRACT FROM AUTHOR]

1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH - formerly TBECH) is an emerging brominated flame retardant (BFR) pollutant with androgen potentiating ability and other endocrine disrupting effects in birds and fish. The objectives of this study were to determine the effects of exposure to environmentally-relevant levels of DBE-DBCH on circulating levels of thyroid and sex steroid hormones in American kestrels, and if hormonal concentrations were related to previously reported changes in reproductive success and courtship behaviors. Sixteen kestrel pairs were exposed to 0.239 ng β-DBE-DBCH/g kestrel/day by diet, based on concentrations in wild bird eggs, from 4 weeks before pairing until the chicks hatched (mean 82 d), and were compared with vehicle-only-exposed control pairs (n=15). As previously reported, DBE-DBCH concentrations were not detected in tissue or eggs of these birds, nor were any potential metabolites, despite the low method limits of detection (≤0.4 ng/g wet weight), suggesting it may be rapidly metabolized and/or eliminated by the kestrels. Nevertheless, exposed kestrels demonstrated changes in reproduction and behavior, indicating an effect from exposure. During early breeding, males were sampled at multiple time points at pairing and during courtship and incubation; females were blood sampled at pairing only; both sexes were sampled at the end of the season. All comparisons are made to control males or control females, and the relative differences in hormone concentrations between treatment and control birds, calculated separately for each sex, are presented for each time point. Males exposed to β-DBE-DBCH demonstrated significantly (p=0.05) lower concentrations of total thyroxine (TT 4 ) overall, that were 11–28% lower than those of control males at the individual sampling points, yet significantly higher (p=0.03) concentrations of free thyroxine (FT 4 ), that were 5–13% higher than those of control males at the individual sampling points; females had similar concentrations of TT 4 and FT 4 at the time of pairing, and T 4 was similar in both sexes at the end of the breeding season. Testosterone (T) concentrations in the treatment males were significantly higher during early (85%) and mid-courtship (30%) (time*treatment p=0.001), whereas females demonstrated a reduction in T at the time of pairing (17%, p=0.05). In the treatment females, concentrations of 17β-estradiol (E 2 ) showed a non-significant decrease (20%) and were positively correlated with T concentrations (p=0.03); E 2 concentrations were below quantification limits in males. For males, some variation in T was also significantly associated with their sexual behavior (p<0.001) and FT 4 concentrations (p=0.01). For females, there was no relationship between hormones measured at pairing and subsequent sexual behaviors or reproductive measures. This study demonstrates that exposure to β-DBE-DBCH at levels that are likely below those experienced by wild birds, affects the thyroid and sex steroid axes in birds and thus may be a contaminant of concern for wildlife warranting further research. [ABSTRACT FROM AUTHOR]

Changes in the sense of agency are defining feature of hypnosis. The Sense of Agency Rating Scale (SOARS) is a 10-item questionnaire, administered after a hypnosis session to assess alteration in the sense of agency. In the present study, a Hungarian version of the measure (SOARS-HU) is presented. The SOARS-HU and the Phenomenology of Consciousness Inventory (PCI) were administered to 197 subjects following hypnotizability screening with the Harvard Group Scale of Hypnotic Susceptibility Scale, Form A (HGSHS:A). Confirmatory factor analysis and correlations with hypnotizability demonstrate the reliability and validity of the SOARS-HU. Changes in the Involuntariness and Effortlessness subscales of the SOARS-HU were associated with alterations in subjective conscious experience, as measured by the PCI. These changes in subjective experience remained significant after controlling for HGSHS:A scores. These results indicate that changes in the sense of agency during hypnosis are associated with alterations of consciousness that are independent of hypnotizability. [ABSTRACT FROM AUTHOR]

Effective and efficient privacy risk management (PRM) is a necessary condition to support digitalization in health care and secondary use of patient data in research. To reduce privacy risks, current PRM frameworks are rooted in an approach trying to reduce undesired technical/organizational outcomes such as broken encryption or unintentional data disclosure. Comparing this with risk management in preventive or therapeutic medicine, a key difference becomes apparent: in health-related risk management, medicine focuses on person-specific health outcomes, whereas PRM mostly targets more indirect, technical/organizational outcomes. In this paper, we illustrate and discuss how a PRM approach based on evidence of person-specific privacy outcomes might look using three consecutive steps: i) a specification of undesired person-specific privacy outcomes, ii) empirical assessments of their frequency and severity, and iii) empirical studies on how effectively the available PRM interventions reduce their frequency or severity. After an introduction of these three steps, we cover their status quo and outline open questions and PRM-specific challenges in need of further conceptual clarification and feasibility studies. Specific challenges of a outcome-oriented approach to PRM include the potential delays between concrete threats manifesting and the resulting person/group-specific privacy outcomes. Moreover, new ways of exploiting privacy-sensitive information to harm individuals could be developed in the future. The challenges described are of technical, legal, ethical, financial and resource-oriented nature. In health research, however, there is explicit discussion about how to overcome such challenges to make important outcome-based assessments as feasible as possible. This paper concludes that it might be the time to have this discussion in the PRM field as well. [ABSTRACT FROM AUTHOR]

The fast and affordable sequencing of large clinical and environmental metagenomic datasets opens up new horizons in medical and biotechnological applications. It is believed that today we have described only about 1% of the microorganisms on the Earth, therefore, metagenomic analysis mostly deals with unknown species in the samples. Microbial communities in extreme environments may contain genes with high biotechnological potential, and clinical metagenomes, related to diseases, may uncover still unknown pathogens and pathological mechanisms in known diseases. While the species-level identification and description of the taxa in the samples do not seem to be possible today, we can search for novel genes with known functions in these samples, using numerous techniques, including artificial intelligence tools, like the hidden Markov models (HMMs). Here we describe a simple-to-use webserver, the MetaHMM, which is capable of homology-based automatic model-building for the genes to be searched for, and it also finds the closest matches in the metagenome. The webserver uses already highly successful building blocks: it performs multiple alignments by applying Clustal Omega, builds a hidden Markov model with HMMER components of hmmbuild and uses hmmsearch for finding similar sequences to the specified model in the metagenomes. The webserver is publicly available at https://metahmm.pitgroup.org. • Metagenomics data yields a rich treasury of genomic information. • Advanced, fast and easy-to-use tools are needed to exploit this plenty. • We present here the MetaHMM webserver for finding new genes in metagenomes. • Hidden Markov Models are applied in the search for still unknown genes. • The webserver is available at https://metahmm.pitgroup.org. [ABSTRACT FROM AUTHOR]

Conventional oil spill recovery may cause significant damage to shoreline habitats during the removal of oiled material and from human and equipment interaction. In addition, these methods are costly and can leave a significant amount of residual oil in the environment. Biological remediation strategies may be a less invasive option for recovering oil from sensitive regions, with potential to increase recovery. Floating treatment wetlands are a growing area of interest for biodegradation of oil facilitated by plant-bacterial partnerships. Plants are able to stimulate microbial colonization in the rhizosphere, creating greater opportunity for contaminant interaction and degradation. A literature review analysis revealed thirteen articles researching this topic, and found that floating treatment wetlands have high potential to degrade oil contaminants. In some instances, plants and inoculated bacteria exhibited the highest degradation potential, however, plants alone had higher degradation potential than bacteria alone. Research is needed to explore how floating treatment wetlands perform in field-based trials and under variable environmental conditions. [Display omitted] • Conventional spill recovery is costly and can be damaging to sensitive habitats. • Floating wetlands may be a successful bioremediation strategy for oil spills. • Plants and bacteria have higher degradation capacity when together than alone. • Future field-based research is needed to test efficacy of this strategy. [ABSTRACT FROM AUTHOR]

Spontaneous fluctuations of resting state functional MRI (rsfMRI) have been widely used to understand the macro-connectome of the human brain. However, these fluctuations are not synchronized among subjects, which leads to limitations and makes utilization of first-level model-based methods challenging. Considering this limitation of rsfMRI data in the time domain, we propose to transfer the spatiotemporal information of the rsfMRI data to another domain, the connectivity domain, in which each value represents the same effect across subjects. Using a set of seed networks and a connectivity index to calculate the functional connectivity for each seed network, we transform data into the connectivity domain by generating connectivity weights for each subject. Comparison of the two domains using a data-driven method suggests several advantages in analyzing data using data-driven methods in the connectivity domain over the time domain. We also demonstrate the feasibility of applying model-based methods in the connectivity domain, which offers a new pathway for the use of first-level model-based methods on rsfMRI data. The connectivity domain, furthermore, demonstrates a unique opportunity to perform first-level feature-based data-driven and model-based analyses. The connectivity domain can be constructed from any technique that identifies sets of features that are similar across subjects and can greatly help researchers in the study of macro-connectome brain function by enabling us to perform a wide range of model-based and data-driven approaches on rsfMRI data, decreasing susceptibility of analysis techniques to parameters that are not related to brain connectivity information, and evaluating both static and dynamic functional connectivity of the brain from a new perspective. [ABSTRACT FROM AUTHOR]

Discoveries of new biomarkers for frequently occurring diseases are of special importance in today's medicine. While fully developed type II diabetes (T2D) can be detected easily, the early identification of high risk individuals is an area of interest in T2D, too. Metagenomic analysis of the human bacterial flora has shown subtle changes in diabetic patients, but no specific microbes are known to cause or promote the disease. Moderate changes were also detected in the microbial gene composition of the metagenomes of diabetic patients, but again, no specific gene was found that is present in disease-related and missing in healthy metagenome. However, these fine differences in microbial taxon- and gene composition are difficult to apply as quantitative biomarkers for diagnosing or predicting type II diabetes. In the present work we report some nucleotide 9-mers with significantly differing frequencies in diabetic and healthy intestinal flora. To our knowledge, it is the first time such short DNA fragments have been associated with T2D. The automated, quantitative analysis of the frequencies of short nucleotide sequences seems to be more feasible than accurate phylogenetic and functional analysis, and thus it might be a promising direction of diagnostic research. [ABSTRACT FROM AUTHOR]

Functional connectivity (FC) patterns obtained from resting-state functional magnetic resonance imaging data are commonly employed to study neuropsychiatric conditions by using pattern classifiers such as the support vector machine (SVM). Meanwhile, a deep neural network (DNN) with multiple hidden layers has shown its ability to systematically extract lower-to-higher level information of image and speech data from lower-to-higher hidden layers, markedly enhancing classification accuracy. The objective of this study was to adopt the DNN for whole-brain resting-state FC pattern classification of schizophrenia (SZ) patients vs. healthy controls (HCs) and identification of aberrant FC patterns associated with SZ. We hypothesized that the lower-to-higher level features learned via the DNN would significantly enhance the classification accuracy, and proposed an adaptive learning algorithm to explicitly control the weight sparsity in each hidden layer via L 1 -norm regularization. Furthermore, the weights were initialized via stacked autoencoder based pre-training to further improve the classification performance. Classification accuracy was systematically evaluated as a function of (1) the number of hidden layers/nodes, (2) the use of L 1 -norm regularization, (3) the use of the pre-training, (4) the use of framewise displacement (FD) removal, and (5) the use of anatomical/functional parcellation. Using FC patterns from anatomically parcellated regions without FD removal, an error rate of 14.2% was achieved by employing three hidden layers and 50 hidden nodes with both L 1 -norm regularization and pre-training, which was substantially lower than the error rate from the SVM (22.3%). Moreover, the trained DNN weights (i.e., the learned features) were found to represent the hierarchical organization of aberrant FC patterns in SZ compared with HC. Specifically, pairs of nodes extracted from the lower hidden layer represented sparse FC patterns implicated in SZ, which was quantified by using kurtosis/modularity measures and features from the higher hidden layer showed holistic/global FC patterns differentiating SZ from HC. Our proposed schemes and reported findings attained by using the DNN classifier and whole-brain FC data suggest that such approaches show improved ability to learn hidden patterns in brain imaging data, which may be useful for developing diagnostic tools for SZ and other neuropsychiatric disorders and identifying associated aberrant FC patterns. [ABSTRACT FROM AUTHOR]

Large data sets are becoming more common in fMRI and, with the advent of faster pulse sequences, memory efficient strategies for data reduction via principal component analysis (PCA) turn out to be extremely useful, especially for widely used approaches like group independent component analysis (ICA). In this commentary, we discuss results and limitations from a recent paper on the topic and attempt to provide a more complete perspective on available approaches as well as discussing various issues to consider related to PCA for very large group ICA. We also provide an analysis of computation time, memory use, and number of dataloads for a variety of approaches under multiple scenarios of small and extremely large data sets. [ABSTRACT FROM AUTHOR]

Spreading depolarizations (SD) are mass depolarizations of neurons and astrocytes that occur spontaneously in acute brain injury and mediate time-dependent lesion growth. Glutamate excitotoxicity has also been extensively studied as a mechanism of neuronal injury, although its relevance to in vivo pathology remains unclear. Here we hypothesized that excitotoxicity in acute lesion development occurs only as a consequence of SD. Using glutamate-sensitive microelectrodes, we found that SD induced by KCl in normal rat cortex elicits increases in extracellular glutamate (11.6 ± 1.3 μM) that are synchronous with the onset, sustainment, and resolution of the extracellular direct-current shift of SD. Inhibition of glutamate uptake with d , l - threo -β-benzyloxyaspartate (TBOA, 0.5 and 1 mM) significantly prolonged the duration of the direct-current shift (148% and 426%, respectively) and the glutamate increase (167% and 374%, respectively) in a dose-dependent manner (P < 0.05). These prolonged events produced significant cortical lesions as indicated by Fluoro-Jade staining (P < 0.05), while no lesions were observed after SD in control conditions or after cortical injection of 1 mM glutamate (extracellular increase: 243 ± 50.8 μM) or 0.5 mM TBOA (glutamate increase: 8.5 ± 1.6 μM) without SD. We then used an embolic focal ischemia model to determine whether glutamate elevations occur independent of SD in the natural evolution of a cortical lesion. In both the ischemic core and penumbra, glutamate increased only in synchrony with anoxic terminal SD (6.1 ± 1.1 μM) and transient SDs (11.8 ± 2.4 μM), and not otherwise. Delayed terminal SDs were also observed in two animals at 98 and 150 min after ischemic onset and induced similar glutamate elevations. Durations of SDs and glutamate increases were significantly correlated in both normal and ischemic animals (P < 0.05). These data suggest that pathologically prolonged SDs are a required mechanism of acute cortical lesion development and that glutamate elevations and the mass electrochemical changes of SD and are merely different facets of the same pathophysiologic process. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) and borderline personality (BPD) disorder share clinical features such as emotional lability and poor interpersonal functioning but the course of illness and treatment differs in these groups, which suggests that the underlying neurobiology of BD and BPD is likely to be different. Understanding the neural mechanisms behind the pathophysiology of BD and BPD will facilitate accurate diagnosis and inform the administration of targeted treatment. Since deficits in social cognition or emotion regulation or in the self-referential processing system can give rise to these clinical features, and impairment in these domains have been observed in both patient groups, functional connectivity within and between networks subserving these processes during resting was investigated using functional magnetic resonance imaging. Data were acquired from 16 patients with BD, 14 patients with BPD, and 13 healthy controls (HC) and functional connectivity strength was correlated with scores using the Difficulties in Emotion Regulation Scale. Functional network connectivity (FNC) patterns differentiated BD and BPD patients from HC. In BD, FNC was increased while in BPD it was decreased. In BD impaired FNC was evident primarily among networks involved in self-referential processing while in BPD it also involved the emotion regulatory network. Impaired FNC displayed an association with impulsivity in BPD and emotional clarity and emotional awareness in BD. This study shows that BD and BPD can perhaps be differentiated using resting state FNC approach and that the neural mechanisms underpinning overlapping symptoms discernibly differ between the groups. These findings provide a potential platform for elucidating the targeted effects of psychological interventions in both disorders. [ABSTRACT FROM AUTHOR]

Abstract: Matrix factorization models are the current dominant approach for resolving meaningful data-driven features in neuroimaging data. Among them, independent component analysis (ICA) is arguably the most widely used for identifying functional networks, and its success has led to a number of versatile extensions to group and multimodal data. However there are indications that ICA may have reached a limit in flexibility and representational capacity, as the majority of such extensions are case-driven, custom-made solutions that are still contained within the class of mixture models. In this work, we seek out a principled and naturally extensible approach and consider a probabilistic model known as a restricted Boltzmann machine (RBM). An RBM separates linear factors from functional brain imaging data by fitting a probability distribution model to the data. Importantly, the solution can be used as a building block for more complex (deep) models, making it naturally suitable for hierarchical and multimodal extensions that are not easily captured when using linear factorizations alone. We investigate the capability of RBMs to identify intrinsic networks and compare its performance to that of well-known linear mixture models, in particular ICA. Using synthetic and real task fMRI data, we show that RBMs can be used to identify networks and their temporal activations with accuracy that is equal or greater than that of factorization models. The demonstrated effectiveness of RBMs supports its use as a building block for deeper models, a significant prospect for future neuroimaging research. [Copyright &y& Elsevier]

Abstract: Recent work on both task-induced and resting-state functional magnetic resonance imaging (fMRI) data suggests that functional connectivity may fluctuate, rather than being stationary during an entire scan. Most dynamic studies are based on second-order statistics between fMRI time series or time courses derived from blind source separation, e.g., independent component analysis (ICA), to investigate changes of temporal interactions among brain regions. However, fluctuations related to spatial components over time are of interest as well. In this paper, we examine higher-order statistical dependence between pairs of spatial components, which we define as spatial functional network connectivity (sFNC), and changes of sFNC across a resting-state scan. We extract time-varying components from healthy controls and patients with schizophrenia to represent brain networks using independent vector analysis (IVA), which is an extension of ICA to multiple data sets and enables one to capture spatial variations. Based on mutual information among IVA components, we perform statistical analysis and Markov modeling to quantify the changes in spatial connectivity. Our experimental results suggest significantly more fluctuations in patient group and show that patients with schizophrenia have more variable patterns of spatial concordance primarily between the frontoparietal, cerebellar and temporal lobe regions. This study extends upon earlier studies showing temporal connectivity differences in similar areas on average by providing evidence that the dynamic spatial interplay between these regions is also impacted by schizophrenia. [Copyright &y& Elsevier]

One application of imaging genomics is to explore genetic variants associated with brain structure and function, presenting a new means of mapping genetic influences on mental disorders. While there is growing interest in performing genome-wide searches for determinants, it remains challenging to identify genetic factors of small effect size, especially in limited sample sizes. In an attempt to address this issue, we propose to take advantage of a priori knowledge, specifically to extend parallel independent component analysis (pICA) to incorporate a reference (pICA-R), aiming to better reveal relationships between hidden factors of a particular attribute. The new approach was first evaluated on simulated data for its performance under different configurations of effect size and dimensionality. Then pICA-R was applied to a 300-participant (140 schizophrenia (SZ) patients versus 160 healthy controls) dataset consisting of structural magnetic resonance imaging (sMRI) and single nucleotide polymorphism (SNP) data. Guided by a reference SNP set derived from ANK3, a gene implicated by the Psychiatric Genomic Consortium SZ study, pICA-R identified one pair of SNP and sMRI components with a significant loading correlation of 0.27 (p=1.64×10−6). The sMRI component showed a significant group difference in loading parameters between patients and controls (p=1.33×10−15), indicating SZ-related reduction in gray matter concentration in prefrontal and temporal regions. The linked SNP component also showed a group difference (p=0.04) and was predominantly contributed to by 1030 SNPs. The effect of these top contributing SNPs was verified using association test results of the Psychiatric Genomic Consortium SZ study, where the 1030 SNPs exhibited significant SZ enrichment compared to the whole genome. In addition, pathway analyses indicated the genetic component majorly relating to neurotransmitter and nervous system signaling pathways. Given the simulation and experiment results, pICA-R may prove a promising multivariate approach for use in imaging genomics to discover reliable genetic risk factors under a scenario of relatively high dimensionality and small effect size. [ABSTRACT FROM AUTHOR]

Highlights: [•] We developed a new, psychometric measure of agency: the Sense of Agency Rating Scale. [•] We identified two components of sense of agency: Involuntariness and Effortlessness. [•] SOARS scores correlate with hypnotisability and passing hypnotic items of different types. [•] The SOARS offers an empirical method for indexing agency in a range of contexts. [ABSTRACT FROM AUTHOR]

Abstract: Connectivity analysis using functional magnetic resonance imaging (fMRI) data is an important area, useful for the identification of biomarkers for various mental disorders, including schizophrenia. Most studies to date have focused on resting data, while the study of functional connectivity during task and the differences between task and rest are of great interest as well. In this work, we examine the graph-theoretical properties of the connectivity maps constructed using spatial components derived from independent component analysis (ICA) for healthy controls and patients with schizophrenia during an auditory oddball task (AOD) and at extended rest. We estimate functional connectivity using the higher-order statistical dependence, i.e., mutual information among the ICA spatial components, instead of the typically used temporal correlation. We also define three novel topological metrics based on the modules of brain networks obtained using a clustering approach. Our experimental results show that although the schizophrenia patients preserve the small-world property, they present a significantly lower small-worldness during both AOD task and rest when compared to the healthy controls, indicating a consistent tendency towards a more random organization of brain networks. In addition, the task-induced modulations to topological measures of several components involving motor, cerebellum and parietal regions are altered in patients relative to controls, providing further evidence for the aberrant connectivity in schizophrenia. [Copyright &y& Elsevier]

Abstract: Recently, deriving candidate endophenotypes from brain imaging data has become a valuable approach to study genetic influences on schizophrenia (SZ), whose pathophysiology remains unclear. In this work we utilized a multivariate approach, parallel independent component analysis, to identify genomic risk components associated with brain function abnormalities in SZ. 5157 candidate single nucleotide polymorphisms (SNPs) were derived from genome-wide array based on their possible connections with SZ and further investigated for their associations with brain activations captured with functional magnetic resonance imaging (fMRI) during a sensorimotor task. Using data from 92 SZ patients and 116 healthy controls, we detected a significant correlation (r=0.29; p=2.41×10−5) between one fMRI component and one SNP component, both of which significantly differentiated patients from controls. The fMRI component mainly consisted of precentral and postcentral gyri, the major activated regions in the motor task. On average, higher activation in these regions was observed in participants with higher loadings of the linked SNP component, predominantly contributed to by 253 SNPs. 138 identified SNPs were from known coding regions of 100 unique genes. 31 identified SNPs did not differ between groups, but moderately correlated with some other group-discriminating SNPs, indicating interactions among alleles contributing toward elevated SZ susceptibility. The genes associated with the identified SNPs participated in four neurotransmitter pathways: GABA receptor signaling, dopamine receptor signaling, neuregulin signaling and glutamate receptor signaling. In summary, our work provides further evidence for the complexity of genomic risk to the functional brain abnormality in SZ and suggests a pathological role of interactions between SNPs, genes and multiple neurotransmitter pathways. [Copyright &y& Elsevier]

Abstract: The anterior cingulate cortex (ACC) is commonly separated into two functional divisions: the cognitive division, which lies in the caudal region and the affective division, which lies in the rostral region of the ACC. Both regions of the ACC are engaged during error-monitoring tasks; however, little is known about the temporal sequencing associated with cognition and affective processes during error-monitoring. Here we use joint Independent Component Analysis (jICA) to couple event-related potential (ERP) time courses and functional magnetic resonance imaging (fMRI) spatial maps to examine the spatio-temporal stages of engagement in the two divisions of the ACC during error-monitoring. Consistent with hypotheses, two of the five significant spatio-temporal components identified by jICA revealed that the error-related negativity (ERN) ERP was associated with distinct spatial fMRI patterns in the ACC. The ERN1 was associated with activity in the caudal ACC and lateral prefrontal cortex (lPFC) while the ERN2 was associated with activity in the rostral ACC. These results suggest that during error-monitoring the caudal ACC and lPFC engage prior to the rostral ACC. These results suggest that cognition precedes affect during error-monitoring. [Copyright &y& Elsevier]

Abstract: Much attention has been paid recently to the role of anomalous experiences in the aetiology of certain types of psychopathology, e.g. in the formation of delusions. We examine, instead, the top-down influence of pre-existing beliefs and affective factors in shaping an individual’s characterisation of anomalous sensory experiences. Specifically we investigated the effects of paranormal beliefs and alexithymia in determining the intensity and quality of an altered state of consciousness (ASC). Fifty five participants took part in a sweat lodge ceremony, a traditional shamanic ritual which was unfamiliar to them. Participants reported significant alterations in their state of consciousness, quantified using the ‘APZ’ questionnaire, a standardized measure of ASC experience. Participants endorsing paranormal beliefs compatible with shamanic mythology, and those showing difficulty identifying feelings scored higher on positive dimensions of ASC experience. Our findings demonstrate that variation in an individual’s characterisation of anomalous experiences is nuanced by pre-existing beliefs and affective factors. [Copyright &y& Elsevier]

Abstract: Let T be a tree all of whose internal vertices have degree at least three. In 1983 Jamison conjectured in JCT B that the average order of a subtree of T is at least half the order of T. In this paper a proof is provided. In addition, it is proved that the average order of a subtree of T is at most three quarters the order of T. Several open questions are stated. [Copyright &y& Elsevier]

The toxicity of the nonylphenol polyethoxylate, R-11 and the neonicotinoid insecticide, imidacloprid were evaluated on the crustacean, Ceriodaphnia dubia Richard. These compounds were evaluated separately and as a mixture because they are applied for pest control and may exist as a binary mixture in surface water. Acute mortality estimates (48h) were developed followed by population-level studies after chronic exposure. LC50s and 95% CL for R-11 and imidacloprid were 9241 (8521–9842)μg/l and 2.1 (1.1–3.4)μg/l, respectively. In the population study, C. dubia were exposed to concentrations equivalent to the acute LC25 for R-11 (8090μg/l) and imidacloprid (0.3μg/l) separately and as a mixture for 8d. The results of the chronic study indicated that R-11 had a greater impact on population parameters than imidacloprid and the mixture had a greater impact than either compound alone. For example, the total number of individuals at the end of the chronic study was 73%, 19%, and 6% of the control for imidacloprid, R-11, and the binary mixture, respectively. Additionally, exposure to R-11, imidacloprid, and the mixture resulted in 52%, 10%, and 91% reductions in population growth rate compared to the control, respectively. The results of this study indicate that when combined, R-11 and imidacloprid act in a more than additive manner. Therefore, it is important that their potential effects on aquatic organisms be evaluated together. [Copyright &y& Elsevier]

Abstract: The Contrast Transfer Function (CTF) of an image, which modulates images taken from a Transmission Electron Microscope (TEM), is usually determined from the radial average of the power spectrum of the image (Frank, J., Three-dimensional Electron Microscopy of Macromolecular Assemblies, Oxford University Press, Oxford, 2006). The CTF is primarily defined by the defocus. If the defocus estimate is accurate enough then it is possible to demodulate the image, which is popularly known as the CTF correction. However, it is known that the radial average is somewhat attenuated if the image is astigmatic (see Fernando, K.V., Fuller, S.D., 2007. Determination of astigmatism in TEM images. Journal of Structural Biology 157, 189–200) but this distortion due to astigmatism has not been fully studied or understood up to now. We have discovered the exact mathematical relationship between the radial averages of TEM images with and without astigmatism. This relationship is determined by a zeroth order Bessel function of the first kind and hence we can exactly quantify this distortion in the radial averages of signal and power spectra of astigmatic images. The argument to this Bessel function is similar to an aberration function (without the spherical aberration term) except that the defocus parameter is replaced by the differences of the defoci in the major and minor axes of astigmatism. The ill effects due this Bessel function are twofold. Since the zeroth order Bessel function is a decaying oscillatory function, it introduces additional zeros to the radial average and it also attenuates the CTF signal in the radial averages. Using our analysis, it is possible to simulate the effects of astigmatism in radial averages by imposing Bessel functions on idealized radial averages of images which are not astigmatic. We validate our theory using astigmatic TEM images. [Copyright &y& Elsevier]

[Display omitted] • A four gene phylogeny clarifies the relationships of Lethrinids in Micronesia. • The cryptic species Monotaxis heterodon is reported in Micronesia. • The ancestral trophic type of Lethrinidae was most likely "stalkers", low-body with conical teeth. • The radiation of recent Lethrinidae species coincides with the radiation of scleractinian corals. Island communities that rely on reef fish are currently faced with declining marine resources due to unsustainable fishing and climate change. Identification of genetic stocks through phylogenetic analyses has become a growing field of study with conservation implications, but genetic information on reef fish in Micronesia is limited. In this study we focus on Lethrinidae, one of the most commonly fished reef fish families in Micronesia. Our main goal was to establish a phylogeny for Lethrinidae based on Micronesian data with the intent to help future conservation efforts and clarify the evolutionary history of trophic types in this family. Thirty-eight Lethrinidae specimens collected across five Micronesian islands were used to build a phylogeny with three mitochondrial and one nuclear gene. The phylogenetic analyses allowed us to clarify the identity and position of 11 commonly harvested species and provided a novel genetic identification for Monotaxis heterodon in Micronesia. Our improved and dated phylogeny supports a new hypothesis for the ancestral trophic type of emperor fishes: "stalkers" with low-bodies and conical teeth. We correlated the radiation of most Lethrinidae species with the radiation of major scleractinian coral lineages in the middle Miocene, highlighting the tight relationships between declining reefs and the survival of emperor fishes. [ABSTRACT FROM AUTHOR]

Abstract: We have developed a new two-step algorithm to determine the astigmatism of images from transmission electron microscopes (TEMs). Instead of computing the radial average of the power spectrum, we divide the power spectrum of a TEM image 1 to m (typically 32) sectors. We use a technique based on perturbation analysis of the contrast transfer function (CTF) to assimilate sector averages of the power spectrum of an image, which are incoherent in the presence of astigmatism, to a coherent radial average corresponding to a nominal defocus value. This is based on the fact that small defocus change from a nominal value can be considered to be equivalent to a perturbation on the spatial frequency spectra. Thus, instead of measuring the angular defocus variations, we optimise the frequency change required to obtain a coherent radial average. Numerically, this is achieved by minimizing σ 2/σ 1 of a matrix formed from the sector averages, where σ i denotes the ith singular value of the matrix. After the minimisation procedure, the second singular value should be very small compared with the first singular value, indicating that the matrix is nearly rank unity. In the second step, the nominal defocus can be obtained from the coherent radial average using any good defocus estimation program, which assumes zero astigmatism. The defocus value at a sector can be obtained from this nominal defocus value and one of the parameters from the unconstrained optima. Our algorithm is tested on astigmatic images of carbon film, 2D crystals of bacteriorhodopsin and cryo-images of HIV cores. [Copyright &y& Elsevier]

Abstract: Over the past decade there has been interest in the computer representation of global data based on multi-resolution subdivisions of regular polyhedra. A simple and efficient indexing of the cells of such a subdivision, called A3-coordinates, is introduced. These can be used to encode the 4·3 n +2 cells at the nth level of resolution of the octahedral aperture 3 hexagonal discrete global grid using n +3 digits, each digit from the set {−1,0,1}. [Copyright &y& Elsevier]

Abstract: BD16449 lipase is the product of a phospholipid-specific lipase gene expressed in the yeast Pichia pastoris strain DVSA-PLC-004. This type C phospholipid lipase (EC 3.1.4.3) is intended for use in the degumming of edible vegetable oil. BD16449 lipase was tested as a refined test article preparation (DV16449) for its effects on genotoxicity and in acute, inhalation, and subchronic toxicity studies. Dosages ranged from 5000μg/plate for in vitro toxicity studies to 2000mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo (NOAEL of 2000mg/kg/day) resulted in a safety margin of 133,000 based on the conservative estimate of the total human consumption of BD16449 lipase of 0.015mg/kg/day. There was no toxicity reported for any of these studies including additional safety studies. A review of the literature indicates that P. pastoris fulfills recognized safety criteria pertinent to microbial production strains used in the manufacture of food enzyme preparations. The results of the toxicity studies presented herein attest to the safety of BD16449 lipase for use in the degumming of edible vegetable oil. [Copyright &y& Elsevier]

Abstract: Evidence from neuroimaging studies suggests that the right hemisphere of the human brain might be more specialized for attention than the left hemisphere. However, differences between right and left hemisphere in the magnitude of hemodynamic activity (i.e., ‘functional asymmetry’) rarely have been explicitly examined in previous neuroimaging studies of attention. This study used a new voxel-based comparison method to examine hemispheric differences in the amplitude of the hemodynamic response in response to infrequent target, infrequent novel, and frequent standard stimuli during an event-related fMRI auditory oddball task in 100 healthy adult participants. Processing of low probability task-relevant target stimuli, or ‘oddballs’, and low probability task-irrelevant novel stimuli is believed to engage in orienting and attentional processes. It was hypothesized that greater right-hemisphere activation compared to left would be observed to infrequent target and novel stimuli. Consistent with predictions, greater right hemisphere than left frontal, temporal, and parietal lobe activity was observed for target detection and novelty processing. Moreover, asymmetry effects did not differ with respect to age or gender of the participants. The results (1) support the proposal that the right hemisphere is differentially engaged in processing salient stimuli and (2) demonstrate the successful use of a new voxel-based laterality analysis technique for fMRI data. [Copyright &y& Elsevier]

Objective: The orthotopic C6 glioma spheroid implantation model has been used to examine factors of neoangiogenesis, growth factor release, and protease expression as well the effect of antitumor agents. The present study systematically investigates the long-term course of orthotopically implanted C6 spheroid gliomas. Methods: Reaggregated C6 spheroid tumors were implanted into the forebrain of 48 male Sprague–Dawley rats (32 immunocompetent, 16 thymectomized). The animals were examined by MRI at postoperative day (POD) 7, 14, 21, 28, 32, 45, 60, and 70. The MRI protocol included a T2-w and T1-w SE sequence before and after application of contrast medium and a CISS 3D sequence for volumetry. A total of six animals were selected after each MR exam from both groups and sacrificed for HE light microscopy and CD8+ T-lymphocyte, ED1+ macrophage, CD31+ endothelial cell immunohistochemistry. Results: The tumors progressed to reach a maximum volume on day 28: 0.23 ± 0.05 ml in the thymectomized and 0.16 ± 0.021 ml in the immunocompetent group. Tumors then consistently regressed to vanish completely by POD 70. The influx of cytotoxic CD8+ T-lymphocytes correlated with tumor progression and the tumors reached a larger size in the thymectomized group. However, the time course of tumor regression was the same for both groups. Conclusion: The present data suggest that the orthotopic C6 glioma implanted into Sprague–Dawley rats will progress within a time span of approximately 4 weeks and can then retrogress again spontaneously. This finding has to be taken into account when deciding on a study protocol and the appropriate animal model. The C6 glioma model may be suitable to study the cell biological steps involved in the phenomenon of spontaneous tumor regression. [Copyright &y& Elsevier]

Although selenium is required by vertebrates, toxicity can arise at concentrations only slightly greater than those they require. The toxicity of Se is thought to arise from its ability to substitute for sulfur during the assembly of proteins. However, recent studies also indicate that some forms of selenium are capable of generating oxidative stress in an in vitro test system that includes glutathione. l-Selenomethionine, the predominant form of selenium in the eggs of oviparous vertebrates, does not generate oxidative radicals in this system, but lesions consistent with oxidative stress have been identified in fish and birds with high concentrations of Se. Here we report on the ability of rainbow trout embryos to transform l-Selenomethionine to a form capable of producing a superoxide radical. Oxidative stress appears to be generated by methioninase enzyme activity in the embryos that liberates methylselenol from l-Selenomethionine. Methylselenol redox cycles in the presence of glutathione producing superoxide and likely accounts for oxidative lesions present in fish and birds environmentally exposed to excessive loads of selenomethionine. [Copyright &y& Elsevier]

Inflammatory events in the central nervous system (CNS) contribute to the disease process in a variety of neuroinflammatory diseases such as multiple sclerosis (MS), Alzheimer’s Disease (AD), and cerebral ischemia, and activated macrophages/microglia are central to this response. Immunological activation of these cells leads to the production of a wide array of cytokines, chemokines, matrix metalloproteinases and neurotoxins, and ultimately to glial/neuronal injury and death. The CD40 molecule has an important role in promoting inflammatory responses by macrophages/microglia, since interaction with its cognate ligand, CD154, leads to secretion of cytokines and neurotoxins. Aberrant CD40 expression by macrophages/microglia, induced by cytokines such as IFN-γ and TNF-α, contributes to neuroimmunologic cascades in the CNS. Strategies to suppress CD40 expression may attenuate inflammation and neuronal damage within the CNS, which will ultimately be of benefit in neuroinflammatory diseases. The mediators that regulate expression of CD40 in macrophages/microglia (both induction and inhibition) function at the level of gene transcription. In this review, we present an overview of the molecular basis of CD40 expression in macrophages/microglia. The signal transduction pathways and transcription factors employed by IFN-γ and TNF-α to induce CD40 expression are described, as are the cis-elements in the CD40 promoter that are critical for CD40 transcription. Information is provided on the mechanism(s) underlying suppression of CD40 in macrophages/microglia by immunomodulatory agents such as IL-4, TGF-β, neuropeptides, neurotrophins, and statins. A comprehensive assessment of CD40 production and function in macrophages/microglia will establish the foundation for future therapeutic manipulation of this critical immunoregulatory protein. [Copyright &y& Elsevier]

BD006 phytase is the product of the Escherichia coli B appA gene expressed in Schizosaccharomyces pombe strain ASP595-1. This enzyme preparation is intended for use in animal feed applications where it improves the bioavailability of phosphate for monogastric animals. BD006 phytase was tested as an unrefined (DV006U) and a refined (DV006R) preparation for its effects on genotoxicity and in acute, inhalation and subchronic toxicity studies. Dosages ranged from 5000 μg/plate for in vitro toxicity studies to a high of 2000X for oral in vivo toxicity studies. The highest oral dose tested (2000X) is 2000 times the highest expected consumption of product by poultry or swine (X=50 units of phytase per kg bwt/day). There was no genotoxicity or any in vivo toxicity reported which could be directly related to systemic effects of the product. Other additional safety studies conducted were devoid of any relevant toxicity. The historic safety profile of the production organism S. pombe, and the results of the toxicity studies presented herein, attest to the safety of BD006 phytase for use in animal feed applications. [Copyright &y& Elsevier]

For a graph G, a graph recurrence sequence x0,x1,x2,… of vectors is defined by the recurrencext+1=Axt, t=0,1,…,where A is the adjacency matrix of G and x0 is an initial vector. Each vector in this sequence can be thought of as a vertex labeling of G, the label at a given vertex at step t+1 obtained by summing the values at the adjacent vertices at step t. Based on graphical sequences, three concepts are defined: (1) for a graph to be determined by a set of vectors, (2) for two graphs to be m-equivalent, and (3) for the vertices of the graph to be separated by a set of vectors. Results concerning these notions are given, relations to the graph isomorphism problem are discussed, and numerous open problems are posed. [Copyright &y& Elsevier]

Let f be an n-variable polynomial with positive integer coefficients, and let H={H1,H2,…,Hm} be a set system on the n-element universe. We define a set system f(H)={G1,G2,…,Gm} and prove that f(Hi1∩Hi2∩⋯∩Hik)=&z.sfnc;Gi1∩Gi2∩⋯∩Gik&z.sfnc;, for any 1&les;k&les;m, where f(Hi1∩Hi2∩⋯∩Hik) denotes the value of f on the characteristic vector of Hi1∩Hi2∩⋯∩Hik. The construction of f(H) is a straightforward polynomial-time algorithm from the set system H and the polynomial f. In this paper we use this algorithm for constructing set systems with prescribed intersection sizes modulo an integer. As a by-product of our method, some upper bounds on the number of sets in set systems with prescribed intersection sizes are extended. [Copyright &y& Elsevier]

I. Danelisen, V. Palace, H. Lou and P. K. Singal. Maintenance of Myocardial Levels of Vitamin A in Heart Failure due to Adriamycin. Journal of Molecular and Cellular Cardiology (2002) 34, 789–795. The therapeutic use of adriamycin (doxorubicin), a potent antitumor antibiotic, is limited by the development of dose-dependent cardiomyopathy. Increased oxidative stress due to adriamycin is considered to play a role in the pathogenesis of this toxic effect. In this study, we examined the levels and redistribution of vitamin A (a potent non-enzymatic antioxidant) in adriamycin-induced cardiomyopathy in rats. Three weeks after the adriamycin (ADR) treatment, animals were hemodynamically assessed and different tissues were analyzed for total retinol (vitamin A), 3H-radio-labeled retinol, retinol palmitate and vitamin E. At 3 weeks, animals in the ADR group were hemodynamically and clinically confirmed to be in heart failure. In the ADR group, total retinol levels in heart and plasma were unchanged. However, levels of the 3H radio-labeled fraction of retinol were significantly increased in both organs suggesting increased turnover. In the liver, the levels of total retinol and retinol palmitate were significantly decreased, while the radio-labeled fraction of retinol was significantly increased suggesting mobilization of retinol from this organ. Alpha tocopherol (vitamin E) levels were found unchanged in hearts of the ADR animals, while its levels in the plasma and liver were significantly increased. Increased radio-labeled fraction, without any change in the total retinol in the heart, suggested that vitamin A is utilized more by the heart under increased oxidative stress due to adriamycin. Its levels in the plasma and the heart may have been maintained at the expense of the loss from the liver. [ABSTRACT FROM AUTHOR]

We prove a version of the Ray-Chaudhuri–Wilson and Frankl–Wilson theorems for k-wise intersections and also generalize a classical code-theoretic result of Delsarte for k-wise Hamming distances. A set of code-words a1, a2,…,ak of length n have k-wise Hamming-distance ℓ, if there are exactly ℓ such coordinates, where not all of their coordinates coincide (alternatively, exactly n−ℓ of their coordinates are the same). We show a Delsarte-like upper bound: codes with few k-wise Hamming-distances must contain few code-words. [Copyright &y& Elsevier]

Previous studies have shown that tumour necrosis factor α (TNF-α) genetranscription is induced in the mouse kidney in response to Shiga-like toxin 1 (Stx 1, or Verotoxin 1, VT1) administration, suggesting that local TNF-α expression plays a role in renal pathogenesis caused by the toxin. Further, TNF-α neutralizing antibody pretreatment of mice orally infected with VT-producing Escherichia coli (VTEC) protected the animals from disease development and death. We examined the role of TNF-α release in response to parenteral challenge with purified VT1. Mice injected with 10- and 100-fold the 50% lethal dose (LD50) of VT1 showed a weak, transient elevation of serum TNF-α only at the higher toxin dose. TNF-α was not detected in the urine of mice at either dose. Treatment of BALB/c mice with a neutralizing anti-TNF-α antibody prior to administration of 3 LD50 of toxin failed to protect the mice from VT1-mediated toxicity. Further, TNF-α knock-out mice administered 3 LD50 of VT1 were not protected against the lethal effects of the toxin relative to the wild-type animals. These findings suggest that VT1 is a poor inducer of TNF-αin vivo and that the low levels of the cytokine released in response to toxin challenge do not play a direct role in potentiating the toxicity of VT1 in mice. Strong toxin accumulation in the kidney but not in the brain was demonstrated by immunohistochemistry after intraperitoneal administration of VT1. Tubular damage and extensive apoptosis in the kidney, together with a 10-fold increase in levels of blood urea nitrogen, suggest that mice died of acute renal failure. [Copyright &y& Elsevier]

Perinataland juvenile oral treatment of rats with methoxychlor (MXC) only during development reduces testicular size and Sertoli cell number in those animals as adults. The objectives were to determine if MXC administered orally reduces numbers of spermatogonia and daily sperm production that parallel reduction in Sertoli cell number and if germ cell degeneration rate or function of individual Sertoli cells was also affected. Rat dams were gavaged with MXC at 0, 5, 50, or 150 mg/kg/day for the week before and after they gave birth. Resulting male pups (14–16 per group) then were dosed directly from postnatal day 7 to 42. Testes were fixed in Bouin''s fixative, postfixed in osmium tetroxide, and embedded in Epon. Sections of 0.5 and 20 μm were evaluated stereologically. Across dose groups, body weight was not affected, but testicular weight was significantly reduced in a dose-dependent fashion. Spermatogenic potential based on number of spermatogonia and number of spermatids per testis was significantly reduced by treatment. There was no adverse effect on daily sperm production per gram of parenchyma based on spermatids; however, the number of spermatogonia per gram was reduced. The ratio of spermatid number per spermatogonia was higher in the MXC-treated groups. This difference indicated that the testis can compensate for the treatment-induced reduction in number of spermatogonia by reducing degeneration of their progeny. However, the reduced number of Sertoli cells prevented the compensation from recovering the daily sperm production per testis totally. Given that endocrine disruptors like MXC can induce compensation during spermatogenesis, it may reduce the ability of the testis to compensate during subsequent exposures. [Copyright &y& Elsevier]

ABSTRACTFive multichannel hematology analyzers (four different models) were evaluated to determine the ability of analyzers to correctly measure packed cell volume (PCV) values across the clinically relevant range. A sixth analyzer (fifth model) was subsequently included using archival data. Twenty-two different blood samples with PCVs ranging from 0.2 to 0.6 L/L were run in duplicate on each analyzer. Duplicate reference PCV determinations were also done using the recently described ICSH-recommended reference method. Simultaneously, a simpler “surrogate reference” procedure was performed in duplicate. Analyzer values were compared to ICSH reference and to surrogate reference PCV values using Deming regression analysis. Compared to either reference, all analyzers showed a slope of less than 1.0, thereby overestimating the PCV at 0.2 L/L and underestimating the PCV at 0.6 L/L to some extent. This outcome was surprising. Deming regression slopes would be expected to average at 1.0. Instruments whose slopes are significantly less than 1.0 will show decreased sensitivity to both anemic and polycythemic patients. We know of no inherent reason why multichannel analyzers should behave in this fashion. [Copyright &y& Elsevier]