Temporal perception deficits in schizophrenia: integration is the problem, not deployment of attentions

Patients with schizophrenia are known to have impairments in sensory processing. In order to understand the specific temporal perception deficits of schizophrenia, we investigated and determined to what extent impairments in temporal integration can be dissociated from attention deployment using Attentional Blink (AB). Our findings showed that there was no evident deficit in the deployment of attention in patients with schizophrenia. However, patients showed an increased temporal integration deficit within a hundred-millisecond timescale. The degree of such integration dysfunction was correlated with the clinical manifestations of schizophrenia. There was no difference between individuals with/without schizotypal personality disorder in temporal integration. Differently from previous studies using the AB, we did not find a significant impairment in deployment of attention in schizophrenia. Instead, we used both theoretical and empirical approaches to show that previous findings (using the suppression ratio to correct for the baseline difference) produced a systematic exaggeration of the attention deficits. Instead, we modulated the perceptual difficulty of the task to bring the baseline levels of target detection between the groups into closer alignment. We found that the integration dysfunction rather than deployment of attention is clinically relevant, and thus should be an additional focus of research in schizophrenia

Dutch translation and cross-cultural validation of the Adult Social Care Outcomes Toolkit (ASCOT)

Background: The Adult Social Care Outcomes Toolkit was developed to measure outcomes of social care in England. In this study, we translated the four level self-completion version (SCT-4) of the ASCOT for use in the Netherlands and performed a cross-cultural validation. Methods: The ASCOT SCT-4 was translated into Dutch following international guidelines, including two forward and back translations. The resulting version was pilot tested among frail older adults using think-aloud interviews. Furthermore, using a subsample of the Dutch ACT-study, we investigated test-retest reliability and construct validity and compared response distributions with data from a comparable English study. Results: The pilot tests showed that translated items were in general understood as intended, that most items were reliable, and that the response distributions of the Dutch translation and associations with other measures were comparable to the original English version. Based on the results of the pilot tests, some small modifications and a revision of the Dignity items were proposed for the final translation, which were approved by the ASCOT development team. The complete original English version and the final Dutch translation can be obtained after registration on the ASCOT website (http://www.pssru.ac.uk/ascot). Conclusions: This study provides preliminary evidence that the Dutch translation of the ASCOT is valid, reliable and comparable to the original English version. We recommend further research to confirm the validity of the modified Dutch ASCOT translation

Geomorphological evolution of a debris‐covered glacier surface

There exists a need to advance our understanding of debris‐covered glacier surfaces over relatively short timescales due to rapid, climatically induced areal expansion of debris cover at the global scale, and the impact debris has on mass balance. We applied unpiloted aerial vehicle structure‐from‐motion (UAV‐SfM) and digital elevation model (DEM) differencing with debris thickness and debris stability modelling to unravel the evolution of a 0.15 km2 region of the debris‐covered Miage Glacier, Italy, between June 2015 and July 2018. DEM differencing revealed widespread surface lowering (mean 4.1 ± 1.0 m a‐1; maximum 13.3 m a‐1). We combined elevation change data with local meteorological data and a sub‐debris melt model, and used these relationships to produce high resolution, spatially distributed maps of debris thickness. These maps were differenced to explore patterns and mechanisms of debris redistribution. Median debris thicknesses ranged from 0.12 to 0.17 m and were spatially variable. We observed localized debris thinning across ice cliff faces, except those which were decaying, where debris thickened. We observed pervasive debris thinning across larger, backwasting slopes, including those bordered by supraglacial streams, as well as ingestion of debris by a newly exposed englacial conduit. Debris stability mapping showed that 18.2–26.4% of the survey area was theoretically subject to debris remobilization. By linking changes in stability to changes in debris thickness, we observed that slopes that remain stable, stabilize, or remain unstable between periods almost exclusively show net debris thickening (mean 0.07 m a‐1) whilst those which become newly unstable exhibit both debris thinning and thickening. We observe a systematic downslope increase in the rate at which debris cover thickens which can be described as a function of the topographic position index and slope gradient. Our data provide quantifiable insights into mechanisms of debris remobilization on glacier surfaces over sub‐decadal timescales, and open avenues for future research to explore glacier‐scale spatiotemporal patterns of debris remobilization

The Use of Orthologous Sequences to Predict the Impact of Amino Acid Substitutions on Protein Function

Computational predictions of the functional impact of genetic variation play a critical role in human genetics research. For nonsynonymous coding variants, most prediction algorithms make use of patterns of amino acid substitutions observed among homologous proteins at a given site. In particular, substitutions observed in orthologous proteins from other species are often assumed to be tolerated in the human protein as well. We examined this assumption by evaluating a panel of nonsynonymous mutants of a prototypical human enzyme, methylenetetrahydrofolate reductase (MTHFR), in a yeast cell-based functional assay. As expected, substitutions in human MTHFR at sites that are well-conserved across distant orthologs result in an impaired enzyme, while substitutions present in recently diverged sequences (including a 9-site mutant that “resurrects” the human-macaque ancestor) result in a functional enzyme. We also interrogated 30 sites with varying degrees of conservation by creating substitutions in the human enzyme that are accepted in at least one ortholog of MTHFR. Quite surprisingly, most of these substitutions were deleterious to the human enzyme. The results suggest that selective constraints vary between phylogenetic lineages such that inclusion of distant orthologs to infer selective pressures on the human enzyme may be misleading. We propose that homologous proteins are best used to reconstruct ancestral sequences and infer amino acid conservation among only direct lineal ancestors of a particular protein. We show that such an “ancestral site preservation” measure outperforms other prediction methods, not only in our selected set for MTHFR, but also in an exhaustive set of E. coli LacI mutants

Structural correlations in bacterial metabolic networks

<p>Abstract</p> <p>Background</p> <p>Evolution of metabolism occurs through the acquisition and loss of genes whose products acts as enzymes in metabolic reactions, and from a presumably simple primordial metabolism the organisms living today have evolved complex and highly variable metabolisms. We have studied this phenomenon by comparing the metabolic networks of 134 bacterial species with known phylogenetic relationships, and by studying a neutral model of metabolic network evolution.</p> <p>Results</p> <p>We consider the 'union-network' of 134 bacterial metabolisms, and also the union of two smaller subsets of closely related species. Each reaction-node is tagged with the number of organisms it belongs to, which we denote organism degree (OD), a key concept in our study. Network analysis shows that common reactions are found at the centre of the network and that the average OD decreases as we move to the periphery. Nodes of the same OD are also more likely to be connected to each other compared to a random OD relabelling based on their occurrence in the real data. This trend persists up to a distance of around five reactions. A simple growth model of metabolic networks is used to investigate the biochemical constraints put on metabolic-network evolution. Despite this seemingly drastic simplification, a 'union-network' of a collection of unrelated model networks, free of any selective pressure, still exhibit similar structural features as their bacterial counterpart.</p> <p>Conclusions</p> <p>The OD distribution quantifies topological properties of the evolutionary history of bacterial metabolic networks, and lends additional support to the importance of horizontal gene transfer during bacterial metabolic evolution where new reactions are attached at the periphery of the network. The neutral model of metabolic network growth can reproduce the main features of real networks, but we observe that the real networks contain a smaller common core, while they are more similar at the periphery of the network. This suggests that natural selection and biochemical correlations can act both to diversify and to narrow down metabolic evolution.</p

Influence of the postoperative inflammatory response on cognitive decline in elderly patients undergoing on-pump cardiac surgery: a controlled, prospective observational study

BACKGROUND: The role of non-infective inflammatory response (IR) in the aetiology of postoperative cognitive dysfunction (POCD) is still controversial. The aim of this controlled, prospective observational study was to assess the possible relationship between the grade of IR, defined by procalcitonin (PCT) changes, and development of POCD related to cardiac surgery. METHODS: Forty-two patients, who were >/= 60 years of age and scheduled for elective cardiac surgery, were separated into the low inflammatory (LIR) and high inflammatory (HIR) response groups based on their PCT levels measured on the first postoperative day. A matched normative control group of 32 subjects was recruited from primary care practice. The PCT and C-reactive protein (CRP) levels were monitored daily during the first five postoperative days. The cognitive function and mood state were preoperatively tested with a set of five neurocognitive tests and two mood inventories and at the seventh postoperative day. The Reliable Change Index modified for practice (RCIp) using data from normative controls was applied to determine the significant decline in test performance. RESULTS: The LIR (n = 20) and HIR (n = 22) groups differed significantly in the PCT (p 0.05). Additionally, there was no difference in the mood states, anxiety levels and perioperative parameters known to influence the development of POCD. CONCLUSIONS: In this study, the magnitude of the non-infective inflammatory response generated by on-pump cardiac surgery did not influence the development of POCD in the early postoperative period in elderly patients

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Biofortified red mottled beans (Phaseolus vulgaris L.) in a maize and bean diet provide more bioavailable iron than standard red mottled beans: Studies in poultry (Gallus gallus) and an in vitro digestion/Caco-2 model

<p>Abstract</p> <p>Background</p> <p>Our objective was to compare the capacities of biofortified and standard colored beans to deliver iron (Fe) for hemoglobin synthesis. Two isolines of large-seeded, red mottled Andean beans (<it>Phaseolus vulgaris </it>L.), one standard ("Low Fe") and the other biofortified ("High Fe") in Fe (49 and 71 μg Fe/g, respectively) were used. This commercial class of red mottled beans is the preferred varietal type for most of the Caribbean and Eastern and Southern Africa where almost three quarters of a million hectares are grown. Therefore it is important to know the affect of biofortification of these beans on diets that simulate human feeding studies.</p> <p>Methods</p> <p>Maize-based diets containing the beans were formulated to meet the nutrient requirements for broiler except for Fe (Fe concentrations in the 2 diets were 42.9 ± 1.2 and 54.6 ± 0.9 mg/kg). One day old chicks (<it>Gallus gallus</it>) were allocated to the experimental diets (n = 12). For 4 wk, hemoglobin, feed-consumption and body-weights were measured.</p> <p>Results</p> <p>Hemoglobin maintenance efficiencies (HME) (means ± SEM) were different between groups on days 14 and 21 of the experiment (P < 0.05). Final total body hemoglobin Fe contents were different between the standard (12.58 ± 1.0 mg {0.228 ± 0.01 μmol}) and high Fe (15.04 ± 0.65 mg {0.273 ± 0.01 μmol}) bean groups (P < 0.05). At the end of the experiment, tissue samples were collected from the intestinal duodenum and liver for further analyses. Divalent-metal-transporter-1, duodenal-cytochrome-B, and ferroportin expressions were higher and liver ferritin was lower (P < 0.05) in the standard group vs. the biofortified group. <it>In-vitro </it>analysis showed lower iron bioavailability in cells exposed to standard ("Low Fe") bean based diet.</p> <p>Conclusions</p> <p>We conclude that the <it>in-vivo </it>results support the <it>in-vitro </it>observations; biofortified colored beans contain more bioavailable-iron than standard colored beans. In addition, biofortified beans seems to be a promising vehicle for increasing intakes of bioavailable Fe in human populations that consume these beans as a dietary staple. This justifies further work on the large-seeded Andean beans which are the staple of a large-region of Africa where iron-deficiency anemia is a primary cause of infant death and poor health status.</p

The Crystal Structure and RNA-Binding of an Orthomyxovirus Nucleoprotein

Genome packaging for viruses with segmented genomes is often a complex problem. This is particularly true for influenza viruses and other orthomyxoviruses, whose genome consists of multiple negative-sense RNAs encapsidated as ribonucleoprotein (RNP) complexes. To better understand the structural features of orthomyxovirus RNPs that allow them to be packaged, we determined the crystal structure of the nucleoprotein (NP) of a fish orthomyxovirus, the infectious salmon anemia virus (ISAV) (genus Isavirus). As the major protein component of the RNPs, ISAV-NP possesses a bi-lobular structure similar to the influenza virus NP. Because both RNA-free and RNA-bound ISAV NP forms stable dimers in solution, we were able to measure the NP RNA binding affinity as well as the stoichiometry using recombinant proteins and synthetic oligos. Our RNA binding analysis revealed that each ISAV-NP binds ,12 nts of RNA, shorter than the 24ﾖ28 nts originally estimated for the influenza A virus NP based on population average. The 12-nt stoichiometry was further confirmed by results from electron microscopy and dynamic light scattering. Considering that RNPs of ISAV and the influenza viruses have similar morphologies and dimensions, our findings suggest that NP-free RNA may exist on orthomyxovirus RNPs, and selective RNP packaging may be accomplished through direct RNA-RNA interactions

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO