bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case-control design identifies ecological drivers of endemic coral diseases
Authors: Caldwell Jamie M. , Aeby Greta , Heron Scott F. , Donahue Megan J. 
Published: June 2019

AbstractEndemic disease transmission is an important ecological process that is challenging to study because of low occurrence rates. Here, we investigate the ecological drivers of two coral diseases -- growth anomalies and tissue loss -- affecting five coral species. We first show that a statistical framework called the case-control study design, commonly used in epidemiology but rarely applied to ecology, provided high predictive accuracy (67-82%) and disease detection rates (60-83%) compared with a traditional statistical approach that yielded high accuracy (98-100%) but low disease detection rates (0-17%). Using this framework, we found evidence that 1) larger corals have higher disease risk; 2) shallow reefs with low herbivorous fish abundance, limited water motion, and located adjacent to watersheds with high fertilizer and pesticide runoff promote low levels of growth anomalies, a chronic coral disease; and 3) wave exposure, stream exposure, depth, and low thermal stress are associated with tissue loss disease risk during interepidemic periods. Variation in risk factors across host-disease pairs suggests that either different pathogens cause the same gross lesions in different species or that the same disease may arise in different species under different ecological conditions.
Dynamic Size-Weight Changes After Object Lifting Reduce the Size-Weight Illusion
Authors: van Polanen Vonne , Davare Marco 
Published: June 2019

ABSTRACTIn the size-weight illusion, the smaller object from two equally weighted objects is typically perceived as being heavier. One explanation is that the mismatch between the weight expectation based on object size and actual sensory feedback influences heaviness perception. In most studies, the size of an object is perceived before its weight. We investigated whether size changes would influence weight perception if both would be perceived simultaneously. We used virtual reality to change the size and weight of an object after lifting and asked participants to judge whether objects became lighter or heavier. We found that simultaneous size-weight changes greatly reduced the size-weight illusion to perceptual biases below discrimination thresholds. In a control experiment in which we used a standard size-weight illusion protocol with sequential lifts of small and large objects in the same virtual reality setup, we found a larger, typical perceptual bias. These results show that the size-weight illusion is smaller when size and weight information is perceived simultaneously. This provides support for the prediction mismatch theory explaining the size-weight illusion. Furthermore, these findings suggest that the lifting phase is a critical time window during which brain mechanisms comparing perceived and expected weight mediate the size-weight illusion.
Stratifying major depressive disorder by polygenic risk for schizophrenia in relation to structural brain measures
Authors: Harris Mathew A. , Shen Xueyi , Cox Simon R. , Gibson Jude , Adams Mark J. , Clarke Toni-Kim , Deary Ian J. , Lawrie Stephen M. , McIntosh Andrew M. , Whalley Heather C. 
Published: June 2019

AbstractBackgroundSubstantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.MethodsThe present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2,370 male and 2,574 female UK Biobank participants.ResultsThere was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β=.191, q=.043). This was driven by apositiveassociation between SCZ PRS and RACC thickness among MDD cases (β=.098, p=.026), compared to a negative association among controls (β=–.087, p=.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.ConclusionsOur significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
Genetic, morphometric, and molecular analyses of interspecies differences in head shape and hybrid developmental defects in the wasp genusNasonia
Authors: Cohen Lorna B , Edwards Rachel , Moody Dyese , Arsala Deanna , Werren Jack H , Lynch Jeremy A 
Published: June 2019

AbstractMales in the parasitoid wasp genusNasonia(N. vitripennis, N. giraulti, N. longicornis) have distinct, species specific, head shapes. Fertile hybrids among the species are readily produced in the lab allowing genetic analysis of the evolved differences. In addition, the obligate haploidy of males makes these wasps a uniquely powerful model for analyzing the role of complex gene interactions in development and evolution. Previous analyses have shown that complex gene interactions underpin different aspects of the shape differences, and developmental incompatibilities that are specific to the head in F2 haploid hybrid males are also governed by networks of gene interaction. Here we use the genetic tools available inNasoniato extend our understanding of the gene interactions that affect development and morphogenesis in male heads. Using artificial diploid male hybrids, we show that alleles affecting head shape are codominant, leading to uniform, averaged hybrid F1 diploid male heads, while the alleles mediating developmental defects are recessive, and are not visible in the diploid hybrids. We also determine that divergence in time, rather than in morphological disparity is the primary driver of hybrid developmental defects. In addition, we show that doublesex is necessary for the male head shape differences, but is not the only important factor. Finally we demonstrate that we can dissect complex interspecies gene interaction networks using introgression in this system. These advances represent significant progress in the complex web of gene interactions that govern morphological development, and chart the connections between genomic and phenotypic variation.
Misfolded α-synuclein causes hyperactive respiration without functional deficit in live neuroblastoma cells
Authors: Ugalde C.L , Annesley S.J , Gordon S , Mroczek K , Perugini M.A , Lawson V.A , Fisher P.R , Finkelstein D.I , Hill A.F 
Published: June 2019

AbstractThe misfolding and aggregation of the largely disordered protein, α-synuclein, is a central pathogenic event that occurs in the synucleinopathies; a group of neurodegenerative disorders that includes Parkinson’s disease. While there is a clear link between protein misfolding and neuronal vulnerability, the precise pathogenic mechanisms employed by disease-associated α-synuclein are unresolved. Here, we studied the pathogenicity of misfolded α-synuclein produced using the Protein Misfolding Cyclic Amplification (PMCA) assay. To do this, previous published methods were adapted to allow PMCA-induced protein fibrillization to occur under non-toxic conditions. Insight into potential intracellular targets of misfolded α-synuclein was obtained using an unbiased lipid screen of 15 biologically relevant lipids that identified cardiolipin (CA) as a potential binding partner for PMCA-generated misfolded α-synuclein. To investigate if such an interaction can impact the properties of α-synuclein misfolding, protein fibrillization was carried out in the presence of the lipid. We show CA both accelerates the rate of α-synuclein fibrillization and produces species that harbour enhanced resistance to proteolysis. Because CA is virtually exclusively expressed in the inner mitochondrial membrane, we then assessed the ability of these misfolded species to alter mitochondrial respiration in live non-transgenic SH-SY5Y neuroblastoma cells. Extensive analysis revealed misfolded α-synuclein causes hyperactive mitochondrial respiration without causing any functional deficit. These data give strong support for the mitochondrion as a target for misfolded α-synuclein and reveals persistent, hyperactive respiration as a potential up-stream pathogenic event associated with the synucleinopathies.Summary statementMisfolded α-synuclein that was produced using the Protein Misfolding Cyclic Amplification (PMCA) assay was found to associate with cardiolipin and cause hyperactive respiration in neuronal cells.
The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia
Authors: Yang Yunpeng , Lang Nannan , Zhang Huan , Zhang Lu , Chai Changsheng , Jiang Weihong , Gu Yang 
Published: June 2019

ABSTRACTSmall noncoding RNAs (sncRNAs) are crucial regulatory molecules in organisms and are well known not only for their roles in the control of diverse essential biological processes but also for their value in genetic modification. However, to date, in gram-positive anaerobic solventogenic clostridia (which are a group of important industrial bacteria with exceptional substrate and product diversity), sncRNAs remain minimally explored, leading to a lack of detailed understanding regarding these important molecules and their use as targets for genetic improvement. Here, we performed large-scale phenotypic screens of a transposon-mediated mutant library ofClostridium acetobutylicum, a typical solventogenic clostridial species, and discovered a novel sncRNA (sr8384) that functions as a determinant positive regulator of growth and solvent synthesis. Comparative transcriptomic data combined with genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator and controls multiple targets that are associated with crucial biological processes, through direct or indirect interactions. Notably, modulation of the expression level of either sr8384 or its core target genes significantly increased the growth rate, solvent titer and productivity of the cells, indicating the importance of sr8384-mediated regulatory network inC. acetobutylicum. Furthermore, a homolog of sr8384 was discovered and proven to be functional in another importantClostridiumspecies,C. beijerinckii, suggesting the potential broad role of this sncRNA in clostridia. Our work showcases a previously unknown potent and complex role of sncRNAs in clostridia, providing new opportunities for understanding and engineering these anaerobes, including pathogenicClostridiumspecies.IMPORTANCEThe discovery of sncRNAs as new resources for functional studies and strain modifications are promising strategies in microorganisms. However, these crucial regulatory molecules have hardly been explored in industrially important solventogenic clostridia. Here, we identified sr8384 as a novel determinant sncRNA controlling cellular performance of solventogenicClostridium acetobutylicumand performed detailed functional analysis, which is the most in-depth study of sncRNAs in clostridia to date. We reveal the pleiotropic function of sr8384 and its multiple direct and indirect crucial targets, which represents a valuable source for understanding and optimizing this anaerobe. Of note, manipulation of these targets leads to improved cell growth and solvent synthesis. Our findings provide a new perspective for future studies on regulatory sncRNAs in clostridia.
The GATA3 X308_Splice breast cancer mutation is a hormone context-dependent oncogenic driver
Authors: Hruschka Natascha , Subijana Maria , Graña-Castro Osvaldo , Del Cano-Ochoa Francisco , Brunet Laia Paré , Sagrera Ana , De Reynies Aurelien , Andreu David , Sutton Joe , Chernukhin Igor , Chin Suet-Feung , Caldas Carlos , Lluch Ana , Burgués Octavio , Bermejo Begoña , Ramón-Maiques Santiago , Carroll Jason S , Prat Aleix , Real Francisco X , Martinelli Paola 
Published: June 2019

AbstractAs the catalogue of oncogenic driver mutations is expanding, it is becoming clear that alterations in a given gene should not be lumped into one single class, since they might have different functions. The transcription factorGATA3is a paradigm of this. Here, we address the functions of the most commonGATA3mutation (X308_Splice) which generates a neoprotein that we designate as neoGATA3, associated with good patient prognosis. Based on extensive analyses of molecular and clinical data from approximately 3000 breast cancer patients, supported by mechanistic studiesin vitro, we show that neoGATA3 interferes with the transcriptional programs controlled by estrogen and progesterone receptors, without fully abrogating them. This has opposite outputs in the pre- or post-menopausal hormonal context, having pro- or anti-proliferative effects, respectively. NeoGATA3 is an example of a context- and stage-dependent driver mutation. Our data call for functional analyses of putative cancer drivers to guide clinical application.
Vital role for Plasmodium berghei Kinesin8B in axoneme assembly during male gamete formation and mosquito transmission
Authors: Depoix D. , Marques S.R. , Ferguson D.J.P. , Chaouch S. , Duguet T. , Sinden R.E. , Grellier P. , Kohl L. 
Published: June 2019

SummarySexual development is an essential phase in the Plasmodium life cycle, where male gametogenesis is an unusual and extraordinarily rapid process. It produces 8 haploid motile microgametes, from a microgametocyte within 15 minutes. Its unique achievement lies in linking the assembly of 8 axonemes in the cytoplasm to the three rounds of intranuclear genome replication, forming motile microgametes, which are expelled in a process called exflagellation. Surprisingly little is known about the actors involved in these processes. We are interested in kinesins, molecular motors that could play potential roles in male gametogenesis. We have undertaken a functional characterization in Plasmodium berghei of kinesin-8B (PbKIN8B) expressed specifically in male gametocytes and gametes. By generating Pbkin8B-gfp parasites, we show that PbKIN8B is specifically expressed during male gametogenesis and is associated with the axoneme. We created a ΔPbkin8B knockout cell line and analysed the consequences of the absence of PbKIN8B on male gametogenesis. We show that the ability to produce sexually differentiated gametocytes is not affected in ΔPbkin8B parasites and that the 3 rounds of genome replication occur normally. Nevertheless, the development to free motile microgametes is halted and the life cycle is interrupted in vivo. Ultrastructural analysis revealed that intranuclear mitoses is unaffected whereas cytoplasmic microtubules, although assembled in doublets and elongated, fail to assemble in the normal axonemal “9+2” structure and become motile. Absence of a functional axoneme prevented microgamete assembly and release from the microgametocyte, severely reducing infection of the mosquito vector. This is the first functional study of a kinesin involved in male gametogenesis. These results reveal a previously unknown role for PbKIN8B in male gametogenesis, providing new insights into Plasmodium flagellar formation.
The role of the endoplasmic reticulum in in vivo cancer FDG kinetics
Authors: Scussolini Mara , Cossu Vanessa , Marini Cecilia , Sambuceti Gianmario , Caviglia Giacomo , Piana Michele 
Published: June 2019

ABSTRACTA very recent result obtained by means of an in vitro experiment with cancer cultured cells has configured the endoplasmic reticulum as the preferential site for the accumulation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Such a result is coherent with cell biochemistry and is made more significant by the fact that reticular accumulation rate of FDG is dependent upon extracellular glucose availability. The objective of the present paper was to confirm this result in vivo, using small animal models of CT26 cancer tissues. Specifically, assuming that the endoplasmic reticulum plays a specific functional role in the framework of a three-compartment model for FDG kinetics, we are able to explain positron emission tomography dynamic data in a more reliable way than by means of a standard Sokoloff two-compartment system. This result is made more solid from a computational viewpoint by means of some identifiability considerations based on a mathematical analysis of the compartmental equations.
Socioeconomic factors associated with dysentery in children under-five years from developing countries
Authors: Pinzón-Rondón Ángela María , Zarate-Ardila Carol Jisseth , Parra-Correa Laura , Zarate-Ardila Alisson , Lozada-Calderón Paola , Di Cecco Leire 
Published: June 2019

AbstractObjectiveDysentery represents 10% of all causes of acute diarrhea in the world and recognizing the implied proximal and distal social factors at different levels would impact on every related outcome. Our purpose is to identify mother, household and country characteristics that favor the presence of dysentery in children under 5 years old.MethodsWe conducted a multilevel analysis of data from phase V of the Demographic and Health Survey and the World Bank, which included 38,762 children from 33 countries.ResultsPrevalence of dysentery was 14.74%. GDP per-capita was negative associated (OR= 0.75; 95% CI 0.71-0.78) and Gini index was positive associated (OR= 1.23; 95% CI 1.19-1.28). Additionally, child age (OR= 0.99; 95% CI 0.99-1.00), mother age (OR= 1.01; 95% CI 1.00-1.01), employed mother (OR= 1.11; 95% CI 1.02-1.20), and number of household members (OR= 1.02; 95% CI 1.01-1.03) have significant positive associations with the presence of dysentery, while complete immunization schedule (OR= 0.88; 95% CI 0.81-0.96), duration of breastfeeding (OR= 0.81; 95% CI 0.75-0.89), and type of residence (OR= 0.87; 95% CI 0.79-0.97) have significant negative associations with having the illness. Finally, each of the categories of wealth index showed a significant association with dysentery (p-value < 0.001).ConclusionsLower per capita GDP and higher Gini coefficient are associated with the development of dysentery, regardless of characteristics of children, their mother, and household. Future and present public health programs should address these issues in order to impact on the occurrence of this illness.Author summaryDysentery represents 10% of all causes of acute diarrheal disease. Diarrhea is the fifth cause of worldwide death in children under five years old. It is particularly important to assess and prevent this condition because the early years of life are critical since it is the period when the brain develops most rapidly and has a high capacity for change. Complications associated with dysentery such as malnutrition and convulsive episodes could have a negative effect in this aspect.Our purpose is to identify the country proximal and distal socioeconomic factors that favor the presence of dysentery in children under five years old from low and middle-income developing countries in order to impact on the occurrence of this illness and its related outcomes. Studying associated factors with developing dysentery during an episode of acute diarrhea could be the base upon which we can diminish mortality from this illness through national policies to impact on national, community and household aspects.
Burden of tumor mutations, neoepitopes, and other variants are dubious predictors of cancer immunotherapy response and overall survival
Authors: Wood Mary A. , Weeder Benjamin R. , David Julianne K. , Nellore Abhinav , Thompson Reid F. 
Published: June 2019

ABSTRACTBackgroundTumor mutational burden (TMB, the quantity of aberrant nucleotide sequences a given tumor may harbor) has been associated with response to immune checkpoint inhibitor therapy and is gaining broad acceptance as a result. However, TMB harbors intrinsic variability across cancer types, and its assessment and interpretation are poorly standardized.MethodsUsing a standardized approach, we quantify the robustness of TMB as a metric and its potential as a predictor of immunotherapy response and survival among a diverse cohort of cancer patients. We also explore the additive predictive potential of RNA-derived variants and neoepitope burden, incorporating several novel metrics of immunogenic potential.ResultsWe find that TMB is a partial predictor of immunotherapy response in melanoma and non-small cell lung cancer, but not renal cell carcinoma. We find that TMB is predictive of overall survival in melanoma patients receiving immunotherapy, but not in an immunotherapy-naive population. We also find that it is an unstable metric with potentially problematic repercussions for clinical cohort classification. We finally note minimal additional predictive benefit to assessing neoepitope burden or its bulk derivatives, including RNA-derived sources of neoepitopes.ConclusionsWe find sufficient cause to suggest that the predictive clinical value of TMB should not be overstated or oversimplified. While it is readily quantified, TMB is at best a limited surrogate biomarker of immunotherapy response. The data do not support isolated use of TMB in renal cell carcinoma.
Habitat selection can reduce effects of extreme climatic events in a long‐lived shorebird
Authors: Bailey Liam D. , Ens Bruno J. , Both Christiaan , Heg Dik , Oosterbeek Kees , van de Pol Martijn 
Published: June 2019

Abstract

Changes in the frequency of extreme climatic events (ECEs) can have profound impacts on individual fitness by degrading habitat quality. Organisms may respond to such changes through habitat selection, favouring those areas less affected by ECEs; however, documenting habitat selection in response to ECEs is difficult in the wild due to the rarity of such events and the long‐term biological data required.

Sea level rise and changing weather patterns over the past decades have led to an increase in the frequency of coastal flooding events, with serious consequences for ground nesting shorebirds. Shorebirds therefore present a useful natural study system to understand habitat selection as a response to ECEs. We used a 32‐year study of the Eurasian oystercatcher (Haematopus ostralegus) to investigate whether habitat selection can lead to an increase in nest elevation and minimize the impacts of coastal flooding.

The mean nest elevation of H. ostralegus has increased during the last three decades. We hypothesized that this change has been driven by changes in H. ostralegus territory settlement patterns over time. We compared various possible habitat selection cues to understand what information H. ostralegus might use to inform territory settlement.

There was a clear relationship between elevation and territory settlement in H. ostralegus. In early years, settlements were more likely at low elevations but in more recent years the likelihood of settlement was similar between high and low elevation areas. Territory settlement was associated with conspecific fledgling output and conspecific density. Settlement was more likely in areas of high density and areas with high fledgling output.

This study shows that habitat selection can minimize the effects of increasingly frequent ECEs. However, it seems unlikely that the changes we observe will fully alleviate the consequences of anthropogenic climate change. Rates of nest elevation increase were insufficient to track current increases in maximum high tide (0.5 vs. 0.8 cm/year). Furthermore, habitat selection cues that rely on information from previous breeding seasons (e.g. conspecific fledgling output) may become ineffective as ECEs become more frequent and environmental predictability is diminished.