bluuebunny/crossref_metadata_2025_split huggingface dataset:
EZH2 influences mdDA neuronal differentiation, maintenance and survival
Authors: Wever Iris , von Oerthel Lars , Wagemans Cindy M.R.J. , Smidt Marten P. 
Published: October 2018

AbstractOver the last decade several components have been identified to be differentially expressed in subsets of mesodiencephalic dopaminergic (mdDA) neurons. These differences in molecular profile have been implied to be involved in the selective degeneration of the SNc neurons in Parkinson’s disease. The emergence and maintenance of individual subsets is dependent on different transcriptional programs already present during development. In addition to the influence of transcription factors, recent studies have led to the hypothesis that modifications of histones might also influence the developmental program of neurons. In this study we focus on the histone methyltransferase EZH2 and its role in the development and maintenance of mdDA neurons. We generated two different conditional knock out (cKO) mice; an En1Cre driven cKO, for deletion of Ezh2 in mdDA progenitors and a Pitx3Cre driven cKO, to study the effect of post-mitotic deletion of Ezh2 on mdDA neurons maturation and neuronal survival. During development Ezh2 was found to be important for the generation of the proper amount of TH+ neurons. The loss of neurons primarily affected a rostrolateral population, which is also reflected in the analysis of the subset marks, Ahd2 and Cck. In contrast to early genetic ablation, post-mitotic deletion of Ezh2 did not lead to major developmental defects at E14.5. However, in 6 months old animals Cck was found ectopically in the rostral domain of mdDA neurons and Ahd2 expression was reduced in more mediocaudal positioned cells. In addition, Pitx3Cre driven deletion of Ezh2 led to a progressive loss of TH+ cells in the VTA and these animals display reduced climbing behavior. Together, our data demonstrates that Ezh2 is important for the generation of mdDA neurons during development and that during adult stages Ezh2 is important for the preservation of proper neuronal subset identity and survival.
Resting-State Brain Fluctuation and Functional Connectivity Dissociate Moral Injury from Posttraumatic Stress Disorder
Authors: Sun Delin , Phillips Rachel D. , Mulready Hannah L. , Zablonski Stephen T. , Turner Jessica A. , Turner Matthew D. , McClymond Kathryn , Nieuwsma Jason A. , Morey Rajendra A. 
Published: October 2018

AbstractMoral injury is closely associated with posttraumatic stress disorder (PTSD) and is characterized by disturbances in social and moral cognition. Little is known about the neural underpinnings of moral injury, and whether the neural correlates are different between moral injury and PTSD.A sample of 26 US military veterans (2 females; 28~55 years old) were investigated to determine how moral injury experiences and PTSD symptoms are differentially related to spontaneous fluctuations indexed by low frequency fluctuation (ALFF) as well as functional connectivity during resting-state functional magnetic resonance imaging (fMRI) scanning.ALFF in the left inferior parietal lobule (L IPL) was positively associated with moral injury sub-scores of transgressions, negatively associated with sub-scores of betrayals, and not related with PTSD symptoms. Moreover, functional connectivity between the L IPL and bilateral precuneus was positively related with PTSD symptoms and negatively related with moral injury total scores.Our results provide the first evidence that moral injury and PTSD have dissociable neural underpinnings, and behaviorally distinct sub-components of moral injury are different in neural responses. The findings increase our knowledge of the neural distinctions between moral injury and PTSD and may contribute to developing nosology and interventions for military veterans afflicted with moral injury.
Indirect effects on fitness between individuals that have never met via an extended phenotype
Authors: Fisher David N. , Haines Jessica A. , Boutin Stan , Dantzer Ben , Lane Jeffrey E. , Coltman David W. , McAdam Andrew G. 
Published: October 2018

AbstractInteractions between organisms are ubiquitous and have important consequences for phenotypes and fitness. Individuals can even influence those they never meet, if they have extended phenotypes which mean the environments others experience are altered. North American red squirrels (Tamiasciurus hudsonicus) guard food hoards, an extended phenotype that typically outlives the individual and is almost always inherited by non relatives. Hoarding by previous owners can therefore influence subsequent owners. We found that red squirrels bred earlier and had higher lifetime fitness if the previous owner was a male. This was driven by hoarding behaviour, as males and mid-aged squirrels had the largest hoards, and these effects persisted across owners, such that if the previous owner was male or died in mid-age subsequent occupants had larger hoards. Individuals can, therefore, influence each other’s resource dependent traits and fitness without meeting via extended phenotypes, and so the past can influence contemporary population dynamics.
Alpha-band oscillations reflect external spatial coding for tactile stimuli in sighted, but not in congenitally blind humans
Authors: Schubert Jonathan T.W. , Buchholz Verena N. , Föcker Julia , Engel Andreas K. , Röder Brigitte , Heed Tobias 
Published: October 2018

AbstractWe investigated the function of oscillatory alpha-band activity in the neural coding of spatial information during tactile processing. Sighted humans concurrently encode tactile location in skin-based and, after integration with posture, external spatial reference frames, whereas congenitally blind humans preferably use skin-based coding. Accordingly, lateralization of alpha-band activity in parietal regions during attentional orienting in expectance of tactile stimulation reflected external spatial coding in sighted, but skin-based coding in blind humans. Here, we asked whether alpha-band activity plays a similar role in spatial coding for tactile processing, that is, after the stimulus has been received. Sighted and congenitally blind participants were cued to attend to one hand in order to detect rare tactile deviant stimuli at this hand while ignoring tactile deviants at the other hand and tactile standard stimuli at both hands. The reference frames encoded by oscillatory activity during tactile processing were probed by adopting either an uncrossed or crossed hand posture. In sighted participants, attended relative to unattended standard stimuli suppressed the power in the alpha-band over ipsilateral centro-parietal and occipital cortex. Hand crossing attenuated this attentional modulation predominantly over ipsilateral posterior-parietal cortex. In contrast, although contralateral alpha-activity was enhanced for attended versus unattended stimuli in blind participants, no crossing effects were evident in the oscillatory activity of this group. These findings suggest that oscillatory alpha-band activity plays a pivotal role in the neural coding of external spatial information for touch.
Comparative Modeling of Transcranial Magnetic and Electric Stimulation in Mouse, Monkey, and Human
Authors: Alekseichuk Ivan , Mantell Kathleen , Shirinpour Sina , Opitz Alexander 
Published: October 2018

ABSTRACTTranscranial magnetic stimulation (TMS) and transcranial electric stimulation (TES) are increasingly popular methods to noninvasively affect brain activity. However, their mechanism of action and dose-response characteristics remain under active investigation. Translational studies in animals play a pivotal role in these efforts due to a larger neuroscientific toolset enabled by invasive recordings. In order to translate knowledge gained in animal studies to humans, it is crucial to generate comparable stimulation conditions with respect to the induced electric field in the brain. Here, we conduct a finite element method (FEM) modeling study of TMS and TES electric fields in a mouse, capuchin monkey, and human model. We systematically evaluate the induced electric fields and analyze their relationship to head and brain anatomy. We find that with increasing head size, TMS-induced electric field strength first increases and then decreases according to a two-term exponential function. TES-induced electric field strength strongly decreases from smaller to larger specimen with up to 100x fold differences across species. Our results can serve as a basis to compare and match stimulation parameters across studies in animals and humans.HIGHLIGHTSTranslational research in brain stimulation should account for large differences in induced electric fields in different organismsWe simulate TMS and TES electric fields using anatomically realistic finite element models in three species: mouse, monkey, and humanTMS with a 70 mm figure-8 coil creates an approximately 2-times weaker electric field in a mouse brain than in monkey and human brains, where electric field strength is comparableTwo-electrode TES creates an approximately 100-times stronger electric field in a mouse brain and 3.5-times stronger electric field in a monkey brain than in a human brain
Supply and consumption of glucose 6-phosphate in the chloroplast stroma
Authors: Preiser Alyssa L. , Banerjee Aparajita , Fisher Nicholas , Sharkey Thomas D. 
Published: October 2018

AbstractFructose 6-phosphate is an intermediate in the Calvin-Benson cycle and can be acted on by phosphoglucoisomerase to make glucose 6-phosphate (G6P) for starch synthesis. A high concentration of G6P is favorable for starch synthesis but can also stimulate G6P dehydrogenase initiating the glucose-6-phosphate shunt an alternative pathway around the Calvin-Benson cycle. A low concentration of glucose 6-phosphate will limit this futile cycle. In order to understand the biochemical regulation of plastidic glucose 6-phosphate supply and consumption, we characterized biochemical parameters of two key enzymes, phosphoglucoisomerase (PGI) and G6P dehydrogenase (G6PDH). We have found that the plastidic PGI in has a higherKmfor G6P compared to that for fructose 6-phosphate. TheKmof G6PDH isoform 1 is increased under reducing conditions. The other two isoforms exhibit less redox regulation; isoform 2 is the most inhibited by NADPH. Our results support the conclusion that PGI restricts stromal G6P synthesis limiting futile cycling via G6PDH. It also acts like a one-way valve, allowing carbon to leave the Calvin-Benson cycle but not reenter. We found flexible redox regulation of G6PDH that could regulate the glucose-6-phosphate shunt.HighlightGlucose 6-phosphate stimulates glucose-6-phosphate dehydrogenase. This enzyme is less active during the day but retains significant activity that is very sensitive to the concentration of glucose 6-phopshate.
Species composition and altitudinal distribution of bumble bees (Hymenoptera: Apidae: Bombus) in the East Himalaya, Arunachal Pradesh, India
Authors: Streinzer Martin , Chakravorty Jharna , Neumayer Johann , Megu Karsing , Narah Jaya , Schmitt Thomas , Bharti Himender , Spaethe Johannes , Brockmann Axel 
Published: October 2018

AbstractThe East Himalaya is one of the world’s most biodiverse ecosystems. Yet, very little is known about the abundance and distribution of many plant and animal taxa in this region. Bumble bees are a group of cold-adapted and high altitude insects that fulfill an important ecological and economical function as pollinators of wild and agricultural flowering plants and crops. The Himalayan mountain range provides ample suitable habitats for bumble bees. Himalayan bumble bees have been studied systematically for a few decades now, with the main focus on the western region, while the eastern part of the mountain range received little attention and only a few species are genuinely reported. During a three-year survey, we collected more than 700 bumble bee specimens of 21 species in Arunachal Pradesh, the largest of the north-eastern states of India. We collected a range of species that were previously known from a very limited number of collected specimens, which highlights the unique character of the East Himalayan ecosystem. Our results are an important first step towards a future assessment of species distribution, threat and conservation. We observed clear altitudinal patterns of species diversity, which open important questions about the functional adaptations that allow bumble bees to thrive in this particularly moist region in the East Himalaya.
Entomopathogenic nematodes increase predation success by inducing specific cadaver volatiles that attract healthy herbivores
Authors: Zhang Xi , Machado Ricardo A. R. , Doan Cong Van , Arce Carla C. M. , Hu Lingfei , Robert Christelle A. M. 
Published: October 2018

ABSTRACTHerbivore natural enemies, including predators, parasitoids and parasites, protect plants by regulating herbivore populations. Some parasites can increase their transmission efficiency by manipulating host behavior. Whether natural enemies can manipulate herbivore behavior to increase top-down control, however, is unknown. Here, we investigate if and how the entomopathogenic nematodeHeterorhabditis bacteriophora,an important biocontrol agent, modulates the behavior of the western corn rootworm,Diabrotica virgifera virgifera,a major maize pest, and how these behavioral changes affect the capacity of the nematode to control the rootworm. We found that healthy rootworm larvae are attracted to nematode-infected cadavers shortly before the emergence of the next generation of nematodes. Nematode-infected rootworms release distinct volatile bouquets, including butylated hydroxytoluene (BHT), which attracts rootworms to infected cadavers. In a soil setting, BHT attracts rootworms and reduces nematode resistance, resulting in increased infection rates and rootworm mortality as well as increased nematode reproductive success. Five out of seven tested insect species were found to be attracted to nematode-infected conspecifics, suggesting that attraction of healthy hosts to nematode-infected cadavers is widespread. This study reveals a new facet of the biology of entomopathogenic nematodes that increases their capacity to control a major root pest by increasing the probability of host encounters.
Telomeric dysfunction triggers an unstable growth arrest leading to irreparable genomic lesions and entry into cellular senescence
Authors: Ghadaouia Sabrina , Olivier Marc Alexandre , Martinez Aurélie , Malaquin Nicolas , Cardin Guillaume B , Rodier Francis 
Published: October 2018

ABSTRACTReplicative senescence is the permanent growth arrest caused by gradual telomere attrition occurring at each round of genome replication. Critically shortened telomeres lose their protective shelterin complex and t-loop structure revealing uncapped chromosome ends that are recognized as DNA double-strand breaks causing a p53-dependent DNA damage response (DDR) towards proliferation arrest. Because telomeres are heterogeneous in length within a single cell, the number of short telomeres necessary for senescence onset remains ill defined. Using controlled Tin2-mediated shelterin inactivation, we show that telomere uncapping is not sufficient to trigger senescence. While uncapping generates expected telomeric DNA damage detection, the associated weak DDR allows a rapid bypass of the primary growth arrest and re-entry into the cell cycle despite dysfunctional telomeres. During the ensuing mitosis, fused telomeres lead to additional DNA breaks and to genomic instability including chromosomes bridges or micronuclei, which sustain a secondary entry into stable growth arrest. The loss of p53 prevented both primary and secondary growth arrest, leading to amplified genomic instablility. Our results support a new multistep model for entry into telomere-mediated replicative senescence in normal cells, which is not directly induced by telomere uncapping, but rather by an amplification of DNA lesions caused by telomere fusions that leads to permanent irreparable genome damage.
Periplasmic protein EipA determines envelope stress resistance and virulence inBrucella abortus
Authors: Herrou Julien , Willett Jonathan W. , Fiebig Aretha , Varesio Lydia M. , Czyż Daniel M. , Cheng Jason X. , Ultee Eveline , Briegel Ariane , Bigelow Lance , Babnigg Gyorgy , Kim Youngchang , Crosson Sean 
Published: October 2018

SummaryMolecular components of theBrucella abortuscell envelope play a major role in its ability to infect, colonize and survive inside mammalian host cells. In this study, we have defined a role for a conserved gene of unknown function inB. abortusenvelope stress resistance and infection. Expression of this gene, which we nameeipA,is directly activated by the essential cell cycle regulator, CtrA.eipAencodes a soluble periplasmic protein that adopts an unusual eight-stranded β-barrel fold. Deletion ofeipAattenuates replication and survival in macrophage and mouse infection models, and results in sensitivity to treatments that compromise the integrity of the cell envelope. Transposon disruption of genes required for LPS O-polysaccharide biosynthesis is synthetically lethal witheipAdeletion. This genetic connection between O-polysaccharide andeipAis corroborated by our discovery thateipAis essential inBrucella ovis, a naturally rough species that harbors mutations in several genes required for O-polysaccharide production. Conditional depletion ofeipAexpression inB. ovisresults in a cell chaining phenotype, providing evidence thateipAdirectly or indirectly influences cell division inBrucella. We conclude that EipA is a molecular determinant ofBrucellavirulence that functions to maintain cell envelope integrity and influences cell division.
Assembly of Yeast Spindle Pole Body and its Components Revealed by Electron Cryo-Tomography
Authors: Li Sam , Fernandez Jose-Jesus 
Published: October 2018

AbstractSpindle pole body (SPB) is the microtubule organizing center (MTOC) in yeast. It plays essential roles during many cellular processes, ranging from mitosis to karyogamy. Here, we used electron cryo-tomography (cryo-ET) and image processing to study SPB and its component purified from the budding yeast. The 3D images and models of SPB at various cell cycle stages were reconstructed by cryo-ET and were analyzed. The results reveal SPB as a cylindrical shaped structure composed of multiple layers. The central layers are arranged with a degree of crystalline order. By using subtomogram averaging methods, we studied the purified “sheet” from over-expressed Spc42p. Our analysis of the SPBs and its components provides new insights into the assembly of this organelle and its cellular function as an MTOC.
Genes with high network connectivity are enriched for disease heritability
Authors: Kim Samuel S. , Dai Chengzhen , Hormozdiari Farhad , van de Geijn Bryce , Gazal Steven , Park Yongjin , O’Connor Luke , Amariuta Tiffany , Loh Po-Ru , Finucane Hilary , Raychaudhuri Soumya , Price Alkes L. 
Published: October 2018

AbstractRecent studies have highlighted the role of gene networks in disease biology. To formally assess this, we constructed a broad set of pathway, network, and pathway+network annotations and applied stratified LD score regression to 42 independent diseases and complex traits (average N=323K) to identify enriched annotations. First, we constructed annotations from 18,119 biological pathways, including 100kb windows around each gene. We identified 156 pathway-trait pairs whose disease enrichment was statistically significant (FDR < 5%) after conditioning on all genes and on annotations from the baseline-LD model, a stringent step that greatly reduced the number of pathways detected; most of the significant pathway-trait pairs were previously unreported. Next, for each of four published gene networks, we constructed probabilistic annotations based on network connectivity using closeness centrality, a measure of how close a gene is to other genes in the network. For each gene network, the network connectivity annotation was strongly significantly enriched. Surprisingly, the enrichments were fully explained by excess overlap between network annotations and regulatory annotations from the baseline-LD model, validating the informativeness of the baseline-LD model and emphasizing the importance of accounting for regulatory annotations in gene network analyses. Finally, for each of the 156 enriched pathway-trait pairs, for each of the four gene networks, we constructed pathway+network annotations by annotating genes with high network connectivity to the input pathway. For each gene network, these pathway+network annotations were strongly significantly enriched for the corresponding traits. Once again, the enrichments were largely explained by the baseline-LD model. In conclusion, gene network connectivity is highly informative for disease architectures, but the information in gene networks may be subsumed by regulatory annotations, such that accounting for known annotations is critical to robust inference of biological mechanisms.
Electron Cryo-Tomography Provides Insight into Procentriole Architecture and Assembly Mechanism
Authors: Li Sam , Fernandez Jose-Jesus , Marshall Wallace F. , Agard David A. 
Published: October 2018

SummaryCentriole is an essential structure with multiple functions in cellular processes. Centriole biogenesis and homeostasis is tightly regulated. Using electron cryo-tomography (cryoET) we present the structure of procentrioles fromChlamydomonas reinhardtii. We identified a set of non-tubulin components attached to the triplet microtubule (MT), many are at the junctions of tubules likely to reinforce the triplet. We describe structure of the A-C linker that bridges neighboring triplets. We find that POC1 is an integral component of the A-C linker. Its conserved WD40 β-propeller domain provides sites for attachment to other A-C linker components. The twist of A-C linker results in an iris diaphragm-like motion of the triplets in the longitudinal direction of procentriole. Finally, we identified two assembly intermediates at the growing ends of procentriole allowing us to propose a model for the procentriole assembly. Our results provide a comprehensive structural framework for understanding the molecular mechanisms underpinning procentriole biogenesis and assembly.