bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional diversity in a tritrophic system: Effects on biomass production, variability, and resilience of ecosystem functions
Authors: Ceulemans Ruben , Gaedke Ursula , Klauschies Toni , Guill Christian 
Published: October 2018

AbstractDiverse communities can adjust their trait composition to altered environmental conditions, which may strongly influence their dynamics. Previous studies of trait-based models mainly considered only one or two trophic levels, whereas most natural system are at least tritrophic. Therefore, we investigated how the addition of trait variation to each trophic level influences population and community dynamics in a tritrophic model. Examining the phase relationships between species of adjacent trophic levels informs about the degree of top-down or bottom-up control in non-steady-state situations. Phase relationships within a trophic level highlight compensatory dynamical patterns between functionally different species, which are responsible for dampening the community temporal variability. Furthermore, even without trait variation, our tritrophic model always exhibits regions with two alternative states with either weak or strong nutrient exploitation, and correspondingly low or high biomass production at the top level. However, adding trait variation increased the basin of attraction of the high-production state, and decreased the likelihood of a critical transition from the high-to the low-production state with no apparent early warning signals. Hence, our study shows that trait variation enhances resource use efficiency, production, variability, and resilience of entire food webs.
Hetero-oligomeric CPN60 resembles highly symmetric group I chaperonin structure revealed by Cryo-EM
Authors: Zhao Qian , Zhang Xiang , Sommer Frederik , Ta Na , Wang Ning , Schroda Michael , Cong Yao , Liu Cuimin 
Published: October 2018

AbstractThe chloroplast chaperonin system is indispensable for the biogenesis of Rubisco, the key enzyme in photosynthesis. Using Chlamydomonas reinhardtii as the model system, we revealed that chloroplast chaperonin is consisted of CPN60α, CPN60β1, and CPN60β2, and co-chaperonin is composed of three subunits CPN20, CPN11 and CPN23 in vivo. CPN20 homo-oligomers and all possible other chloroplast co-chaperonin hetero-oligomers are functional, but only CPN11/20/23-CPN60αβ1β2 pair can fully replace GroES/GroEL in E. coli at stringent growth condition. Endogenous CPN60 was purified and its stoichiometry was determined to be 6:2:6 for CPN60α:CPN60β1:CPN60β2. The cryo-EM structures of endogenous CPN60αβ1β2/ADP and CPN60αβ1β2/co-chaperonin/ADP were solved at resolutions of 4.06 Å and 3.82Å, respectively. In both hetero-oligomeric complexes the chaperonin subunits within each ring are highly symmetric. The chloroplast co-chaperonin CPN11/20/23 formed seven GroES-like domains through hetero-oligomerization which symmetrically interact with CPN60αβ1β2. Our structures also reveal an uneven distribution of roof-like structures in the dome-shaped CPN11/20/23 and potentially diversified surface properties in the folding cavity of CPN60αβ1β2 that might enable the chloroplast chaperonin system to assist in the folding of specific substrates.
Genetic signatures of human cytomegalovirus variants acquired by seronegative glycoprotein B vaccinees
Authors: Nelson Cody S. , Cruz Diana Vera , Su Melody , Xie Guanhua , Vandergrift Nathan , Pass Robert F. , Forman Michael , Diener-West Marie , Koelle Katia , Arav-Boger Ravit , Permar Sallie R. 
Published: October 2018

AbstractHuman cytomegalovirus (HCMV) is the most common congenital infection worldwide, and a frequent cause of hearing loss or debilitating neurologic disease in newborn infants. Thus, a vaccine to prevent HCMV-associated congenital disease is a public health priority. One potential strategy is vaccination of women of child-bearing age to prevent maternal HCMV acquisition during pregnancy. The glycoprotein B (gB) + MF59 adjuvant subunit vaccine is the most efficacious tested clinically to date, demonstrating approximately 50% protection against HCMV infection of seronegative women in multiple phase 2 trials. Yet, the impact of gB/MF59-elicited immune responses on the population of viruses acquired by trial participants has not been assessed. In this analysis, we employed quantitative PCR as well as multiple sequencing methodologies to interrogate the magnitude and genetic composition of HCMV populations infecting gB/MF59 vaccinees and placebo recipients. We identified several differences between the viral dynamics of acutely-infected vaccinees and placebo recipients. First, there was reduced magnitude viral shedding in the saliva of gB vaccinees. Additionally, employing a panel of tests for genetic compartmentalization, we noted tissue-specific gB haplotypes in the majority of vaccinees though only in a single placebo recipient. Finally, we observed reduced acquisition of genetically-related gB1, gB2, and gB4 genotype “supergroup” HCMV variants among vaccine recipients, suggesting that the gB1 genotype vaccine construct may have elicited partial protection against HCMV viruses with antigenically-similar gB sequences. These findings indicate that gB immunization may have had a measurable impact on viral intrahost population dynamics and support future analysis of a larger cohort.Author SummaryThough not a household name like Zika virus, human cytomegalovirus (HCMV) causes permanent neurologic disability in one newborn child every hour in the United States - more than Down syndrome, fetal alcohol syndrome, and neural tube defects combined. There are currently no established effective preventative measures to inhibit congenital HCMV transmission following acute or chronic HCMV infection of a pregnant mother. However, the glycoprotein B (gB) vaccine is the most effective HCMV vaccine tried clinically to date. Here, we utilized high-throughput, next-generation sequencing of viral DNA isolated from patients enrolled in a gB vaccine trial, and identified several impacts that this vaccine had on the size, distribution, and composition of thein vivoviral population. These results have increased our understanding of why the gB/MF59 vaccine was partially efficacious and will inform future rational design of a vaccine to prevent congenital HCMV.
Using a large-scale biodiversity monitoring dataset to test the effectiveness of protected areas at conserving North-American breeding birds
Authors: Cazalis Victor , Belghali Soumaya , Rodrigues Ana S.L. 
Published: October 2018

AbstractProtected areas currently cover about 15% of the global land area, and constitute one of the main tools in biodiversity conservation. Quantifying their effectiveness at protecting species from local decline or extinction involves comparing protected with counterfactual unprotected sites representing “what would have happened to protected sites had they not been protected”. Most studies are based on pairwise comparisons, using neighbour sites to protected areas as counterfactuals, but this choice is often subjective and may be prone to biases. An alternative is to use large-scale biodiversity monitoring datasets, whereby the effect of protected areas is analysed statistically by controlling for landscape differences between protected and unprotected sites, allowing a more targeted and clearly defined measure of the protected areas effect. Here we use the North American Breeding Bird Survey dataset as a case study to investigate the effectiveness of protected areas at conserving bird assemblages. We analysed the effect of protected areas on species richness, on assemblage-level abundance, and on the abundance of individual species by modelling how these metrics relate to the proportion of each site that is protected, while controlling for local habitat, altitude, productivity and for spatial autocorrelation. At the assemblage level, we found almost no relationship between protection and species richness or overall abundance. At the species level, we found that forest species are present in significantly higher abundances within protected forest sites, compared with unprotected forests, with the opposite effect for species that favour open habitats. Hence, even though protected forest assemblages are not richer than those of unprotected forests, they are more typical of this habitat. We also found some evidence that species that avoid human activities tend to be favoured by protection, but found no such effect for regionally declining species. Our results highlight the complexity of assessing protected areas effectiveness, and the necessity of clearly defining the metrics of effectiveness and the controls used in such assessments.
Selective sweep and phylogenetic models for the emergence and spread of pyrimethamine resistance mutations inPlasmodium vivax
Authors: Shaukat Ayaz , Ali Qasim , Connelley Timothy , Azmat Ullah Khan Muhammad , Saleem Mushtaq A. , Rashid Imran , Sargison Neil D. , Chaudhry Umer 
Published: October 2018

AbstractPyrimethamine resistance is a major concern for the control of human haemoprotozoa, especiallyPlasmodiumspecies. Currently, there is little understanding of how pyrimethamine resistance developed inPlasmodium vivaxin the natural field conditions. Here, we present first time the evidence of positive selection pressure on a dihydrofolate reductase locus and its consequences on the emergence and the spread of pyrimethamine resistance inP. vivaxin the Punjab province of Pakistan. First, we examined the pyrimethamine resistance locus in 38P. vivaxpopulations to look for evidence of positive selection pressure in human patients. The S58R (AGA)/S117N (AAC) double mutation was most common, being detected in 10/38 populations. Single mutation S117N (AAC), I173L (CTT) and S58R (AGA) SNPs were detected in 8/38, 2/38 and 1/38 populations, respectively. The F57L/I (TTA/ATA) and T61M (ATG) SNPs were not detected in any population examined. Although both soft and hard selective sweeps have occurred with striking differences between populations, there was a predominance of hard sweeps. A single resistance haplotype was present at high frequency in 9/14 populations, providing a strong evidence for the single emergence of these mutations. In contrast, 5/14 populations carried multiple resistance haplotypes at high frequencies, providing an evidence of the emergence of resistance by recurrent mutations, characteristics of soft selective sweeps. Our phylogenetic relationship analysis suggests that S58R (AGA)/S117N (AAC) and S117N (AAC) mutations arose multiple times from a single origin and spread to multiple different cities in the Punjab province through gene flow. Interestingly, the I173L (CTT) mutation was present on a single haplotype, suggesting that it arises rarely and has not spread between cities. Our work shows the need for responsible use of exiting and new antimicrobial drugs and their combinations, control the movement of infected patients and mosquito vector control strategies.
Structural and proteomic changes in viable but non-culturableVibrio cholerae
Authors: Brenzinger Susanne , van der Aart Lizah T. , van Wezel Gilles P. , Lacroix Jean-Marie , Glatter Timo , Briegel Ariane 
Published: October 2018

AbstractAquatic environments are reservoirs of the human pathogenVibrio choleraeO1, which causes the acute diarrheal disease cholera. Upon low temperature or limited nutrient availability, the cells enter a viable but non-culturable (VBNC) state. Characteristic of this state are an altered morphology, low metabolic activity and lack of growth under standard laboratory conditions. Here, for the first time, the cellular ultrastructure ofV. choleraeVBNC cells raised in natural waters was investigated using electron cryo-tomography complemented by comparison of the proteomes and the peptidoglycan composition of LB overnight culture and VBNC cells. The extensive remodeling of the VBNC cells was most obvious in the passive dehiscence of the cell envelope, resulting in improper embedment of flagella and pili. Only minor changes of the peptidoglycan and osmoregulated periplasmic glucans were observed. Active changes in VBNC cells included the production of cluster I chemosensory arrays and change of abundance of cluster II array proteins. Components involved in iron acquisition and storage, peptide import and arginine biosynthesis were overrepresented in VBNC cells, while enzymes of the central carbon metabolism were found at lower levels. Finally, several pathogenicity factors ofV. choleraewere less abundant in the VBNC state, potentially limiting their infectious potential.
Neurons remap to represent memories in the human entorhinal cortex
Authors: Qasim Salman , Miller Jonathan , Inman Cory S. , Gross Robert E. , Willie Jon T. , Lega Bradley , Lin Jui-Jui , Sharan Ashwini , Wu Chengyuan , Sperling Michael R. , Sheth Sameer A. , McKhann Guy M. , Smith Elliot H. , Schevon Catherine , Stein Joel , Jacobs Joshua 
Published: October 2018

AbstractThe entorhinal cortex (EC) is known to play a key role in both memory and spatial navigation. Despite this overlap in spatial and mnemonic circuits, it is unknown how spatially responsive neurons contribute to our ability to represent and distinguish past experiences. Recording from medial temporal lobe (MTL) neurons in subjects performing cued recall of object–location memories in a virtual-reality environment, we identified “trace cells” in the EC that remap their spatial fields to locations subjects were cued to recall on each trial. In addition to shifting its firing field according to the memory cue, this neuronal activity exhibited a firing rate predictive of the cued memory’s content. Critically, this memory-specific neuronal activity re-emerged when subjects were cued for recall without entering the environment, indicating that trace-cell memory representations generalized beyond navigation. These findings suggest a general mechanism for memory retrieval via trace-cell activity and remapping in the EC.
The genetic relationship between female reproductive traits and six psychiatric disorders
Authors: Ni Guiyan , Amare Azmeraw , Zhou Xuan , Mills Natalie , Gratten Jacob , Hong Lee Sang 
Published: October 2018

ABSTRACTFemale reproductive behaviors have an important implication in evolutionary fitness and health of offspring. Previous studies have shown that age at first birth of women (AFB) is genetically associated with schizophrenia (SCZ). However, for most other psychiatric disorders and reproductive traits, the latent shared genetic architecture is largely unknown. Here we used the second wave of UK Biobank data (N=220,685) to evaluate the association between five female reproductive traits and polygenetic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N=429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with AFB (genetic correlation of −0.68 ± 0.03 with p-value = 1.86E-89), age at first sexual intercourse (AFS) (−0.56 ± 0.03 with p-value = 3.42E-60), number of live births (NLB) (0.36 ± 0.04 with p-value = 4.01E-17) and age at menopause (−0.27 ± 0.04 with p-value = 5.71E-13). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (genetic correlation of 0.35 ± 0.06), ED and AFS (0.19 0.06), Major depressive disorder (MDD) and AFB (−0.27 ± 0.07), MDD and AFS (− 0.27 ± 0.03) and SCZ and AFS (−0.10 ± 0.03). Our findings reveal the shared genetic architecture between the five reproductive traits in women and six psychiatric disorders, which have a potential implication that helps to improve reproductive health in women, hence better child outcomes. Our findings may also explain, at least in part, an evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.
Wide and Deep Imaging of Neuronal Activities by a Wearable NeuroImager Reveals Premotor Activity in the Whole Motor Cortex
Authors: Kobayashi Takuma , Islam Tanvir , Sato Masaaki , Ohkura Masamichi , Nakai Junichi , Hayashi Yasunori , Okamoto Hitoshi 
Published: October 2018

SummaryWearable technologies for functional whole brain imaging in freely moving animals would advance our understanding of cognitive processing and adaptive behavior. Fluorescence imaging can visualize the activity of individual neurons in real time, but conventional microscopes have limited sample coverage in both the width and depth of view. Here we developed a novel head-mounted laser camera (HLC) with macro and deep-focus lenses that enable fluorescence imaging at cellular resolution for comprehensive imaging in mice expressing a layer- and cell type-specific calcium probe. We visualized orientation selectivity in individual excitatory neurons across the whole visual cortex of one hemisphere, and cell assembly expressing the premotor activity that precedes voluntary movement across the motor cortex of both hemispheres. Including options for multiplex and wireless interfaces, our wearable, wide- and deep-imaging HLC technology could enable simple and economical mapping of neuronal populations underlying cognition and behavior.
Blood flow-mediated gene transfer and siRNA-knockdown in the developing vasculature in a spatio-temporally controlled manner in chicken embryos
Authors: Takase Yuta , Takahashi Yoshiko 
Published: October 2018

AbstractWe describe a method by which early developing vasculature can be gene-manipulated independently of the heart in a spatio-temporally controlled manner. Lipofectamine 2000 or 3000, an easy-to-use lipid reagent, has been found to yield a high efficiency of transfection when co-injected withGFPDNA within a critical range of lipid concentration. By exploiting developmentally changing patterns of vasculature and blood flow, we have succeed in controlling the site of transfection: injection with a lipid-DNA cocktail into the heart before or after the blood circulation starts results in a limited and widely spread patterns of transfection, respectively. Furthermore, a cocktail injection into the right dorsal aorta leads to transgenesis of the right half of embryonic vasculature. In addition, this method combined with the siRNA technique has allowed, for the first time, to knockdown the endogenous expression ofVE-cadherin(also calledCdh5), which has been implicated in assembly of nasant blood vessels: whenCah5siRNA is injected into the right dorsal aorta, pronounced defects in the right half of vasculature are observed without heart defects. Whereas infusion-mediated gene transfection method has previously been reported using lipid reagents that were elaborately prepared on their own, Lipofectamine is an easy-use reagent with no requirement of special expertise. The methods reported here would overcome shortcomings of conventional vascular-transgenic animals, such as mice and zebrafish, in which pan-endothelial enhancer-driven transgenesis often leads to the heart malformation, which, in turn, indirectly affects peripheral vasculature due to flow defects. Since a variety of subtypes in vasculature have increasingly been appreciated, the spatio-temporally controllable gene manipulation described in this study offers a powerful tool.Research HighlightsBlood flow-mediated transfection enables site-specific transgenesis in vessels.This transfection technique allows local knockdown of endogenous gene(s) by siRNA.Knockdown of endogenousVE-cadherincauses vascular defects without heart failure.
Structural variants identified by Oxford Nanopore PromethION sequencing of the human genome
Authors: Wouter De Coster , Arne De Roeck , Tim De Pooter , Svenn D’Hert , Peter De Rijk , Mojca Strazisar , Sleegers Kristel , Christine Van Broeckhoven 
Published: October 2018

AbstractWe sequenced the Yoruban NA19240 genome on the long read sequencing platform Oxford Nanopore PromethION for benchmarking and evaluation of recently published aligners and structural variant calling tools. In this work, we determined the precision and recall, present high confidence and high sensitivity call sets of variants and discuss optimal parameters. The aligner Minimap2 and structural variant caller Sniffles are both the most accurate and the most computationally efficient tools in our study. We describe our scalable workflow for identification, annotation, and characterization of tens of thousands of structural variants from long read genome sequencing of an individual or population. By discussing the results of this genome we provide an approximation of what can be expected in future long read sequencing studies aiming for structural variant identification.
Brg1 controls neurosensory cell fate commitment and differentiation in the mammalian inner ear
Authors: Xu Jinshu , Li Jun , Eddie Loh Yong-Hwee , Zhang Ting , Jiang Huihui , Fritzsch Bernd , Ramakrishnan Aarthi , Shen Li , Xu Pin-Xian 
Published: October 2018

AbstractOtic ectoderm gives rise to almost all cell types of the inner ear; however, the mechanisms that link transcription factors, chromatin, lineage commitment and differentiation capacity are largely unknown. Here we show that Brg1 chromatin-remodeling factor is required for specifying neurosensory lineage in the otocyst and for inducing hair and supporting cell fates in the cochlear sensory epithelium. Brg1 interacts with the critical neurosensory-specific transcription factors Eya1/Six1, both of which simultaneously interact with BAF60a or BAF60c. Chromatin immunoprecipitation-sequencing (ChIP-seq) and ChIP assays demonstrate Brg1 association with discrete regulatory elements at theEya1andSix1loci.Brg1-deficiency leads to markedly decreased Brg1 binding at these elements and loss ofEya1andSix1expression. Furthermore, ChIP-seq reveals Brg1-bound promoter-proximal and distal regions near genes essential for inner ear morphogenesis and cochlear sensory epithelium development. These findings uncover essential functions for chromatin-remodeling in the activation of neurosensory fates during inner ear development.
High-performance GFP-based calcium indicators for imaging activity in neuronal populations and microcompartments
Authors: Dana Hod , Sun Yi , Mohar Boaz , Hulse Brad , Hasseman Jeremy P. , Tsegaye Getahun , Tsang Arthur , Wong Allan , Patel Ronak , Macklin John J. , Chen Yang , Konnerth Arthur , Jayaraman Vivek , Looger Loren L. , Schreiter Eric R. , Svoboda Karel , Kim Douglas S. 
Published: October 2018

AbstractCalcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics, and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and tracking large populations of neurons using 2-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.