Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of venular microvessel permeability by calcium influx into endothelial cells

It has been proposed that calcium ion influx into endothelial cells modulates the permeability of venular microvessels via a calcium‐dependent contractile process. The results of recent investigations using permeabilized endothelial cell monolayers conform to this hypothesis by demonstrating a calcium‐dependent interaction of endothelial actin and myosin during the retraction of adjacent endothelial cells exposed to inflammatory agents. Little is known about the pathway for calcium influx into endothelial cells after exposure to mediators of inflammation, but evidence suggests that the properties of the calcium entry pathways are similar to the calcium entry pathways that regulate the release of endothelium‐derived relaxing factor (EDRF). Substances that stimulate EDRF release from arterial endothelium also increase venular microvessel permeability. Recently developed methods to measure cytoplasmic calcium concentration in the endothelial cells forming the walls of individually perfused microvessels enable a direct investigation of the modulation of the permeability of venular microvessels by calcium influx. These experiments demonstrate that the magnitude of the initial increase in the permeability of microvessels after exposure to an agent that increases permeability, such as a calcium ionophore, is determined by the magnitude of calcium ion influx into the endothelial cells. Furthermore, the magnitude of the calcium influx into endothelial cells is modulated by the membrane potential of the endothelial cells. Depolarization of the endothelial cell membrane reduces calcium influx and attenuates increases in permeability whereas hyperpolarization of the endothelial membrane increases calcium influx and potentiates increases in permeability. These data conform to the hypothesis that a passive conductance channel for calcium is a major pathway for calcium ion flux responsible to eliciting an increase in the permeability of the endothelial barrier in microvessels. —Curry, F. E. Modulation of venular microvessel permeability by calcium influx into endothelial cells. FASEB J. 6: 2456‐2466; 1992.
Altered development of the brain after focal herpesvirus infection of the central nervous system

Human cytomegalovirus infection of the developing central nervous system (CNS) is a major cause of neurological damage in newborn infants and children. To investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing CNS. Intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. Virus infection of the CNS was associated with the induction of inflammatory responses, including the induction of a large number of interferon-stimulated genes and histological evidence of focal encephalitis with recruitment of mononuclear cells to foci containing virus-infected cells. The morphogenesis of the cerebellum was delayed in infected animals. The defects in cerebellar development in infected animals were generalized and, although correlated temporally with virus replication and CNS inflammation, spatially unrelated to foci of virus-infected cells. Specific defects included decreased granular neuron proliferation and migration, expression of differentiation markers, and activation of neurotrophin receptors. These findings suggested that in the developing CNS, focal virus infection and induction of inflammatory responses in resident and infiltrating mononuclear cells resulted in delayed cerebellar morphogenesis.
Is there evidence that social class at birth increases risk of psychosis? A systematic review

Background: In the 1950s, researchers showed an association between low socio-economic status (SES) and psychosis. Two competing theories social causation and social drift were proposed to explain the findings. In the intervening years, contrasting evidence emerged as some studies showed no association between SES and schizophrenia. At present, the nature of the relationship is still unclear; currently, there are no reviews in the literature examining the association between social class at birth and psychosis. Aim: To search the literature to clarify the relationship between social class at birth, measured by paternal occupation at birth, and the risk of adult-onset psychosis. Methods: A systematic search of the literature using a combination of keywords in Group 1 together with the keywords in Group 2 was performed in October 2012 in the following online databases: (a) MEDLINE (1946–2012), (b) PubMed, (c) Embase (1980–2012), (d) PsycINFO (1806–2012) and (e) Web of Science (1899–2012). Reference lists were also hand searched. The search provided 3,240 studies; following screening of the titles and abstracts by inclusion and exclusion criteria and quality assessment of the full text, 14 studies were identified to be appropriate for the review. The keywords used for the search were as follows: Group 1 – social class, social status, socioeconomic, socio-economic, SES; Group 2 – psychosis, psychoses, schizophrenia. Results: Seven studies showed an association between low SES and psychosis. Four studies showed no association, and three studies showed an association with high SES. Conclusion: There is not enough evidence to support the association between social class and psychosis. While some findings showed an association between low social class and psychosis, there were a number of conflicting studies showing no association or a link with higher social class. Interestingly, the results followed a temporal pattern, as all the studies conducted after 2001 supported an association between low SES at birth and psychosis. Four of the six studies employed a prospective design with large sample populations, indicating the need for further investigation.
Using Gall Wasps on Oaks to Test Broad Ecological Concepts

Abstract: Planning conservation of insect herbivores requires knowing what needs to be conserved and developing a set of predictor variables that aid management. We conducted a state‐wide survey to examine the species richness of gall wasps (Hymenoptera: Cynipidae) on six oak species dominant in the threatened scrub‐oak vegetation in peninsular Florida. Eighty‐eight cynipid species were recorded; 23 were new species to Florida (a 35% increase), including 17 species new to science and 6 species newly recorded in the state. The cynipid species represented 68% of cynipids of Florida, on only 24% of oak species sampled. This fauna represents a hotspot of richness, justifying conservation initiatives in scrub‐oak habitat and throughout the state. We derived predictor variables from general ecological concepts: (1) the theory of island biogeography that insect species richness increases as host plant geographic area increases and as local abundance increases, (2) the plant‐architecture hypothesis that insect species richness increases with increased plant size, and (3) phytochemical patterns in leaves, including nutrients and digestibility reducers predicting suitability for insect herbivores. Concepts 1 and 2, developed for large scales and species numbers, were tested at smaller scales relevant to much conservation research and management. A stepwise multiple regression including all predictor variables accounted for 99% of the variance in cynipid species richness with three variables: foliar hemicellulose concentration (81%), host geographic area (16%), and tree height (2%). The trends were negative, however, and opposite to those predicted by concepts 1 and 2. Ecological theory was not applicable to discovery of predictors of cynipid species richness on six oak species. Thus, we promote caution in applying ecological theory to a narrow set of species without specific testing of how patterns conform to theoretical predictions.
Energy consumption in mine haulage due to road pavement performance

Mine haul road pavements are often designed with informal methods. This approach means the energy consumption in haulage is not quantified and so pavement operating costs are not able to be defined. The energy consumption of haul trucks operating on unbound and cementitiously modified haul road pavement basecourse and wearing courses were estimated with variable traffic, climate and maintenance inputs. Energy consumption estimates showed that significant benefits may arise through the use of superior gravels that contain a suitable fines content with low to medium plasticity in the pavement wearing course. Similarly, it was shown that the pavement structural class significantly impacts haul truck energy consumption. Structural class is determined by pavement design and may be improved by increasing the pavement depth or utilizing stiffer materials. Estimating the energy consumption of haul trucks as part of the pavement design process would allow optimization of capital and operating costs over the life of a haul road.
Overexpression of Q-rich prion-like proteins suppresses polyQ cytotoxicity and alters the polyQ interactome

Significance Expansion of a poly-glutamine (polyQ) repeat is the causal mutation of several inherited neurological disorders, including Huntington’s disease. In a yeast genetic screen, we identified several proteins with Q-rich, prion-like domains that reduce the toxicity of mutant polyQ proteins when overexpressed. One of these, glycine threonine serine repeat protein (Gts1p), was characterized in more detail. Association with Gts1p did not prevent aggregation but altered the physical properties and the interactome of the aggregates. Specifically, Gts1p expression reduced the sequestration of other prion-like proteins into the polyQ aggregates. These findings link polyQ toxicity in yeast with the coaggregation of prion proteins and show that short Q-rich peptides are able to shield toxic forms of polyQ proteins, directing them into nontoxic aggregates. Expansion of a poly-glutamine (polyQ) repeat in a group of functionally unrelated proteins is the cause of several inherited neurodegenerative disorders, including Huntington’s disease. The polyQ length-dependent aggregation and toxicity of these disease proteins can be reproduced in Saccharomyces cerevisiae. This system allowed us to screen for genes that when overexpressed reduce the toxic effects of an N-terminal fragment of mutant huntingtin with 103 Q. Surprisingly, among the identified suppressors were three proteins with Q-rich, prion-like domains (PrDs): glycine threonine serine repeat protein (Gts1p), nuclear polyadenylated RNA-binding protein 3, and minichromosome maintenance protein 1. Overexpression of the PrD of Gts1p, containing an imperfect 28 residue glutamine-alanine repeat, was sufficient for suppression of toxicity. Association with this discontinuous polyQ domain did not prevent 103Q aggregation, but altered the physical properties of the aggregates, most likely early in the assembly pathway, as reflected in their increased SDS solubility. Molecular simulations suggested that Gts1p arrests the aggregation of polyQ molecules at the level of nonfibrillar species, acting as a cap that destabilizes intermediates on path to form large fibrils. Quantitative proteomic analysis of polyQ interactors showed that expression of Gts1p reduced the interaction between polyQ and other prion-like proteins, and enhanced the association of molecular chaperones with the aggregates. These findings demonstrate that short, Q-rich peptides are able to shield the interactive surfaces of toxic forms of polyQ proteins and direct them into nontoxic aggregates.
Synaptic Localization and Activity of ADAM10 Regulate Excitatory Synapses through N-Cadherin Cleavage

N-Cadherin has an important role during dendrite arborization, axon guidance, and synaptogenesis. In particular, at synaptic sites, N-cadherin is involved in the regulation of cell–cell adhesion and in morphology and plasticity control. Recent studies have shown that N-cadherin can be cleaved by the metalloproteinase ADAM10. Here we demonstrate that impairing ADAM10 localization and activity at synaptic sites decreases its processing of N-cadherin. This leads to an accumulation of the full-length form of N-cadherin, to an increase in spine head width, and to modifications of the number and function of glutamate receptors of AMPA type, both in vitro and in vivo. Our results indicate a key role for ADAM10 in the complex sequence of events through which N-cadherin affects spine maturation and controls structure and function of glutamatergic synapses.
Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

Significance Experiences are remembered long-term when these memories are formed in a state of arousal and heightened emotion. The arousal-induced release of noradrenaline is critical for modulating consolidation, the process that establishes long-term memory. Although the effects of pharmacological manipulation of adrenergic signaling on memory stability are already being investigated in the clinical setting, how adrenergic receptors mediate long-term memory consolidation remains unclear. This study reports a previously unidentified mechanism with important translational implications: The noradrenergic receptors that in the hippocampus mediate memory consolidation are β2-adrenergic receptors (β2ARs) expressed in astrocytes. These receptors are necessary for the learning-evoked release of lactate from astrocytes, which then is required to support the neuronal molecular changes essential for long-term memory formation. Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2-adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long-term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.
Diffuse Retinal Pigment Epitheliopathy among the Inhabitants of Brahmaputra Valley of India

Purpose To analyze the patient demography and the various fluorescein angiography (FA) features of diffuse retinal pigment epitheliopathy (DRPE) cases among the inhabitants of the Brahmaputra Valley of India and to see if there is any ethnic variation in its clinical presentation and risk factors. Methods This is a retrospective study in a clinical practice setting with study population of Aryan and Mongoloid races. Data analysis of 30 cases (40 eyes) of DRPE of 262 consecutive cases of central serous chorioretinopathy (CSC) was done. The various features of these cases were compared and statistically evaluated with the findings of CSC cases with symptom duration of 6 months or more and cases with recurrent episodes. Results A total of 11.45% had DRPE that had average symptom duration of 3.50 years. Logistic regression showed high risk for DRPE if sensory retinal detachment (SRD) persists for more than 18 months. Systemic hypertension was another significant risk factor, whereas multiple RPE leaks appeared to be weakly significant. DRPE was predominant in eyes of patients having first acute episode of CSC in later age and fairly large retinal pigment epithelial detachments (PEDs) contributed to its development. Role of exogenous corticosteroid, retinotoxic drugs, and tobacco consumption could not be assessed properly due to inadequate sample size. Conclusions The main factor for the development of DRPE is the persistence of SRD for more than 1.50 years. Fairly large leaking PED and onset of primary CSC in later age appear to contribute towards its development. Except for these, no major variation from Western studies was observed.
A Small World of Citations? The Influence of Collaboration Networks on Citation Practices

This paper examines the proximity of authors to those they cite using degrees of separation in a co-author network, essentially using collaboration networks to expand on the notion of self-citations. While the proportion of direct self-citations (including co-authors of both citing and cited papers) is relatively constant in time and across specialties in the natural sciences (10% of references) and the social sciences (20%), the same cannot be said for citations to authors who are members of the co-author network. Differences between fields and trends over time lie not only in the degree of co-authorship which defines the large-scale topology of the collaboration network, but also in the referencing practices within a given discipline, computed by defining a propensity to cite at a given distance within the collaboration network. Overall, there is little tendency to cite those nearby in the collaboration network, excluding direct self-citations. These results are interpreted in terms of small-scale structure, field-specific citation practices, and the value of local co-author networks for the production of knowledge and for the accumulation of symbolic capital. Given the various levels of integration between co-authors, our findings shed light on the question of the availability of ‘arm's length’ expert reviewers of grant applications and manuscripts.
AGAPE (Automated Genome Analysis PipelinE) for Pan-Genome Analysis of Saccharomyces cerevisiae

The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated. Saccharomyces cerevisiae is an extensively studied model organism, with well-known protein functions and thoroughly curated phenotype data. To develop and expand the available resources linking genomic variation with function in yeast, we aim to model the pan-genome of S. cerevisiae. To initiate the yeast pan-genome, we newly sequenced or re-sequenced the genomes of 25 strains that are commonly used in the yeast research community using advanced sequencing technology at high quality. We also developed a pipeline for automated pan-genome analysis, which integrates the steps of assembly, annotation, and variation calling. To assign strain-specific functional annotations, we identified genes that were not present in the reference genome. We classified these according to their presence or absence across strains and characterized each group of genes with known functional and phenotypic features. The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages. As more S. cerevisiae strain genomes are released, our analysis can be used to collate genome data and relate it to lineage-specific patterns of genome evolution. Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community.
On First-Order Definability and Computability of Progression for Local-Effect Actions and Beyond

In a seminal paper, Lin and Reiter introduced the notion of progression for basic action theories in the situation calculus. Unfortunately, progression is not first-order definable in general. Recently, Vassos, Lakemeyer, and Levesque showed that in case actions have only local effects, progression is first-order representable. However, they could show computability of the first-order representation only for a restricted class. Also, their proofs were quite involved. In this paper, we present a result stronger than theirs that for local-effect actions, progression is always first-order definable and computable. We give a very simple proof for this via the concept of forgetting. We also show first-order definability and computability results for a class of knowledge bases and actions with non-local effects. Moreover, for a certain class of local-effect actions and knowledge bases for representing disjunctive information, we show that progression is not only first-order definable but also efficiently computable.
A Brief History of IL-1 and IL-1 Ra in Rheumatology

The history of what, in 1979, was called interleukin-1 (IL-1), orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP) (1974) and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF) (1977). Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra) in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as “inflammasome” have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still’s disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet’s disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.