bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breakage of Hydrophobic Contacts Limits the Rate of Passive Lipid Exchange Between Membranes
Authors: Rogers Julia R. , Geissler Phillip L. 
Published: May 2020

AbstractThe maintenance of heterogeneous lipid compositions among cellular membranes is key to biological function. Yet, even the simplest process that could be responsible for maintaining proper lipid distributions, passive lipid exchange of individual molecules between membranes, has eluded a detailed understanding, due in part to inconsistencies between experimental findings and molecular simulations. We resolve these discrepancies by discovering the reaction coordinate for passive lipid exchange, which enables a complete biophysical characterization of the rate limiting step for lipid exchange. Our approach to identify the reaction coordinate capitalizes on our ability to harvest over 1,000 unbiased trajectories of lipid insertion, an elementary step of passive lipid transport, using all-atom and coarse-grained molecular dynamics simulations. We find that the reaction coordinate measures the formation and breakage of hydrophobic contacts between the membrane and exchanging lipid. Consistent with experiments, free energy profiles as a function of our reaction coordinate exhibit a substantial barrier for insertion. In contrast, lipid insertion was predicted to be a barrier-less process by previous computational studies, which incorrectly presumed the reaction coordinate to be the displacement of the exchanging lipid from the membrane. Utilizing our newfound knowledge of the reaction coordinate, we formulate an expression for the lipid exchange rate to enable a quantitative comparison with experiments. Overall, our results indicate that the breakage of hydrophobic contacts is rate limiting for passive lipid exchange and provide a foundation to understand the catalytic function of lipid transfer proteins.
Impact of Concatenating fMRI Data on Reliability for Functional Connectomics
Authors: Cho Jae Wook , Korchmaros Annachiara , Vogelstein Joshua T , Milham Michael , Xu Ting 
Published: May 2020

AbstractCompelling evidence suggests the need for more data per individual to reliably map the functional organization of the human connectome. As the notion that ‘more data is better’ emerges as a golden rule for functional connectomics, researchers find themselves grappling with the challenges of how to obtain the desired amounts of data per participant in a practical manner, particularly for retrospective data aggregation. Increasingly, the aggregation of data across all fMRI scans available for an individual is being viewed as a solution, regardless of scan condition (e.g., rest, task, movie). A number of open questions exist regarding the aggregation process and the impact of different decisions on the reliability of resultant aggregate data. We leveraged the availability of highly sampled test-retest datasets to systematically examine the impact of data aggregation strategies on the reliability of cortical functional connectomics. Specifically, we compared functional connectivity estimates derived after concatenating from: 1) multiple scans under the same state, 2) multiple scans under different states (i.e. hybrid or general functional connectivity), and 3) subsets of one long scan. We also varied connectivity processing (i.e. global signal regression, ICA-FIX, and task regression) and estimation procedures. When the total number of time points is equal, and the scan state held constant, concatenating multiple shorter scans had a clear advantage over a single long scan. However, this was not necessarily true when concatenating across different fMRI states (i.e. task conditions), where the reliability from the aggregate data varied across states. Concatenating fewer numbers of states that are more reliable tends to yield higher reliability. Our findings provide an overview of multiple dependencies of data concatenation that should be considered to optimize reliability in analysis of functional connectivity data.
Gamma rhythms and visual information in mouse V1 specifically modulated by somatostatin-positive neurons in reticular thalamus
Authors: Hoseini Mahmood S. , Higashikubo Bryan , Cho Frances S. , Chang Andrew H. , Clemente-Perez Alexandra , Lew Irene , Stryker Michael , Paz Jeanne T. 
Published: May 2020

ABSTRACTVisual perception in natural environments depends on the ability to focus on salient stimuli while ignoring distractions. This kind of selective visual attention is associated with gamma activity in the visual cortex. While the nucleus reticularis thalami (nRT) has been implicated in selective attention, its role in modulating visual perception remains unknown. Here we show that somatostatin-(SOM) but not parvalbumin-expressing (PV) neurons in the nRT preferentially project to visual thalamic nuclei. In freely behaving mice, single-unit and field recordings reveal powerful modulation of both visual information transmission and gamma activity in primary visual cortex (V1), as well as in the dorsal lateral geniculate nucleus (dLGN). These findings pinpoint the SOM neurons in nRT as powerful modulators of the visual information encoding accuracy in V1, and represent a novel circuit through which the nRT can influence representation of visual information.
Physiological characterization of nitrate ammonifying bacteria isolated from rice paddy soil via a newly developed high-throughput screening method
Authors: Heo Hokwan , Kwon Miye , Song Bongkeun , Yoon Sukhwan 
Published: May 2020

ABSTRACTDissimilatory nitrate/nitrite reduction to ammonium (DNRA) has recently gained attention as a nitrogen retention pathway that may potentially be harnessed to alleviate nitrogen loss resulting from denitrification. Until recently, ecophysiology of DNRA bacteria inhabiting agricultural soils has remained largely unexplored, due to the difficulty in targeted enrichment and isolation of DNRA microorganisms. In this study, >100 microbial isolates capable of DNRA have been isolated from rice paddy soil with apparent dominance of denitrification using a novel high-throughput screening method. Six of these isolates, each assigned to a disparate genus, was examined to improve understanding of DNRA physiology. All isolates carriednrfAand/ornirB, and an isolate affiliated toBacilluspossessed a clade IInosZgene and was capable of N2O reduction. A common prominent physiological feature observed in all DNRA isolates was NO2−accumulation observed before NH4+production, which was further examined withCitrobactersp. DNRA3 (possessingnrfAandnirB)andEnterobactersp. DNRA5 (possessing onlynirB). In both organisms, NO2−-to-NH4+reduction was inhibited by submillimolar NO3−, andnrfAornirBtranscription was down-regulated when NO3−was being reduced to NO2−. Both batch and chemostat incubations of these isolates with excess organic electron donors produced NH4+from reduction of NO3−; however, incubation with excess NO3−resulted in NO2−buildup but no substantial NH4+production, presumably due to NO3−presence. This previously overlooked link between NO3−repression of NO2−-to-NH4+reduction and the C-to-N ratio regulation of DNRA activity may be a key mechanism underpinning denitrification-vs-DNRA competition in soil.IMPORTANCEDissimilatory nitrate/nitrite reduction to ammonium (DNRA) is an anaerobic microbial pathway that competes with denitrification for common substrates NO3−and NO2−. Unlike denitrification leading to nitrogen loss and N2O emission, DNRA reduces NO3−and NO2−to NH4+, a reactive nitrogen with higher tendency to be retained in soil matrix. Therefore, stimulation of DNRA has often been proposed as a strategy to improve fertilizer efficiency and reduce greenhouse gas emissions. Such attempts have been hampered by lack of insights into soil DNRA ecophysiology. Here, we have developed a novel high-throughput screening method for isolating DNRA-catalyzing organisms from agricultural soils without apparent DNRA activity. Physiological characteristics of six DNRA isolates were closely examined, disclosing a previously overlooked link between NO3−repression of NO2−-to-NH4+reduction and the C-to-N ratio regulation of DNRA activity, which may be key to understanding why significant DNRA activity is rarely observed in nitrogen-rich agricultural soils.
Clinical Performance of SARS-CoV-2 Molecular Testing
Authors: Green Daniel A. , Zucker Jason , Westblade Lars F. , Whittier Susan , Rennert Hanna , Velu Priya , Craney Arryn , Cushing Melissa , Liu Dakai , Sobieszczyk Magdalena , Boehme Amelia K. , Sepulveda Jorge L. 
Published: May 2020

AbstractMolecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the test clinical performance is poorly understood. From 3/10/2020-5/1/2020 NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed in 3,432 patients, of which 2,413 had negative and 1,019 had positive first day results. Repeat-tested patients were more likely to be older, male, African-American or Hispanic, and to have severe disease. Among the patients with initially negative results, 18.6% became positive upon repeat-testing. Only 58.1% of any-time positive patients had a result of “detected” on the first test. The clinical sensitivity of COVID-19 molecular assays is estimated between 66.2 % and 95.6%, depending on the unknown number of false negative results in single-tested patients. Conversion to a negative result is unlikely to occur before 15 to 20 days after initial testing or 20-30 days after the onset of symptoms, with 50% conversion occurring at 28 days after initial testing. Forty-nine initially-positive patients converted to negative and then back to positive in subsequent days. Conversion from first day negative to positive results increased linearly with each day of testing, reaching 25% probability in 20 days. In summary, our study provides estimates of the clinical performance of SARS-CoV-2 molecular assays and suggests time frames for appropriate repeat testing, namely 15 to 20 days after a positive test and the same or next 2 days after a negative test in a patient with high suspicion for COVID-19.
Transcriptomic response of an Antarctic yeastRhodotorulasp. USM-PSY62 to temperature changes
Authors: Chai Cleo-Nicole , Yam Hok-Chai , Rosli Nurlina , Azlan Azali , Azzam Ghows , Halim Mardani Abdul , Najimudin Nazalan 
Published: May 2020

AbstractRhodotorulasp. (USM-PSY62) is a psychrophilic yeast isolated from Antarctic sea ice and it grows optimally at 15 °C. This study was set up to observe how USM-PSY62 adapted to fluctuations in temperature. During cold adaptation, an elevated transcription of the CorA magnesium transporter gene in USM-PSY62 indicated a higher requirement for magnesium ions in order to gain additional enzyme cofactors or maintain cytoplasmic fluidity. The HepA homologue coding for DNA/RNA helicase was also over-expressed in cold condition possibly to reorganize secondary structures of DNA and RNA. An up-regulation of the catalase gene was also observed reflecting an increment in the concentration of reactive oxygen species and fluctuations in the associated antioxidant system. TheYOP1gene, which encodes a membrane protein associated with protein transport and membrane traffic, was the most down-regulated under cold shock condition. The genes responsible for the structural maintenance of chromosome (SMC) were also down-regulated when the temperature was shifted to 0 °C. Upon cold shock, the gene for heat shock factor protein 1 (HSF1) was also down-regulated. Hsf1 is a transcriptional regulator which regulate the heat shock responses. Although USM-PSY62 showed some common adaptive strategies as in several other psychrophilic organisms, new mechanisms were also uncovered.
Pattern recognition receptors confer plant salt tolerance via WRKY18/WRKY40 transcription factors
Authors: Loo Eliza P. , Tajima Yuri , Yamada Kohji , Hirase Taishi , Ariga Hirotaka , Fujiwara Tadashi , Tanaka Keisuke , Taji Teruaki , Somssich Imre E. , Parker Jane E. , Saijo Yusuke 
Published: May 2020

AbstractPattern recognition receptors (PRRs) bind microbe- and damage-associated molecular patterns (MAMPs/DAMPs, respectively) to enhance host immunity in animals and plants. Here, we report that PRRs also confer salt tolerance in the model plantArabidopsis thalianafollowing recognition of cognate ligands, such as bacterial flagellin and EF-Tu and the endogenous Pep peptides. Pattern-triggered salt tolerance (PTST) requires the PRR-associated kinasesBAK1andBIK1, and the NADPH oxidaseRBOHD. Transcriptome profiling reveals an inventory of PTST target genes, which increase or acquire salt responsiveness following an exposure to immunogenic patterns. In their regulatory DNA sequences, specific binding sites for a subset of WRKY transcription factors are over-represented. Accordingly, PTST requiresWRKY40andWRKY18, which activate salt tolerance-related genes but attenuate pathogen defense-related genes, including theEDS1immunity activator. PRR signaling leads to sustained WRKY40/WRKY18 accumulation under salt stress and utilizes bothWRKYs for salt tolerance. The PRR-WRKY40/WRKY18 module also confers salt tolerance after challenge with non-pathogenic bacteria. Our findings give molecular insight into signaling plasticity underlying biotic-abiotic stress cross-tolerance in plants conferred by PRRs.
Third generation indexing for third generation sequencing
Authors: Jighly Abdulqader 
Published: May 2020

AbstractIndexing of DNA sequences is the art of sorting massive genomic data in a user-friendly structure to enable rapid accessing and comparing of different patterns in the data. Current genome assemblers use general algorithms for string indexing that do not exploit the special structural arrangement of genomes. Here, I am proposing a new algorithm that indexes only the configuration of microsatellite motifs along reads assuming that the order of microsatellites will be the same in overlapped sequences. The index size is >1000 times smaller than currently used indices and it has higher tolerance to the high error rates produced by third generation sequencing platforms. The results showed that the proposed algorithm can rapidly detect overlaps among considerable proportion of uncorrected long reads (~50% of all simulated base pairs with average read size of 8.16 kb and total error rates of 14.4%) to build large initial contigs. Unassembled reads can be then mapped to these contigs or can be assembled with them with currently used algorithms. Thus, the proposed algorithm can efficiently be used as an initial stage to significantly reduce the number of pairwise sequence comparisons among reads and/or references and improve the performance of different software but not replacing them. The algorithm was also useful for comparative genomics and detect large locally colinear blocks and structural variations among tensaccharomyces cerevisiaestrains. The proposed algorithm has the power to make de novo assembly of individuals as routine activity which can lead to more accurate variant calling and pan genomics.
RAN translation of the expanded CAG repeats in the SCA3 disease context
Authors: Jazurek-Ciesiolka Magdalena , Ciesiolka Adam , Komur Alicja A. , Urbanek-Trzeciak Martyna O. , Fiszer Agnieszka 
Published: May 2020

ABSTRACTSpinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in theATXN3gene encoding the ataxin-3 protein. Despite extensive research the exact pathogenic mechanisms of SCA3 are still not understood in depth. In the present study, to gain insight into the toxicity induced by the expanded CAG repeats in SCA3, we comprehensively investigated repeat-associated non-ATG (RAN) translation in various cellular models expressing translated or non-canonically translatedATXN3sequences with an increasing number of CAG repeats. We demonstrate that two SCA3 RAN proteins, polyglutamine (polyQ) and polyalanine (polyA), are found only in the case of CAG repeats of pathogenic length. Despite having distinct cellular localization, RAN polyQ and RAN polyA proteins are very often coexpressed in the same cell, impairing nuclear integrity and inducing apoptosis. We provide for the first time mechanistic insights into SCA3 RAN translation indicating thatATXN3sequences surrounding the repeat region have an impact on SCA3 RAN translation initiation and efficiency. We revealed that RAN translation of polyQ proteins starts at non-cognate codons upstream of the CAG repeats, whereas RAN polyA proteins are likely translated within repeats. Furthermore, integrated stress response activation enhances SCA3 RAN translation. We suggest that RAN translation in SCA3 is a common event substantially contributing to SCA3 pathogenesis and that theATXN3sequence context plays an important role in triggering this unconventional translation.
Why is cyclic dominance so rare?
Authors: Park Hye Jin , Pichugin Yuriy , Traulsen Arne 
Published: May 2020

AbstractNatural populations can contain multiple types of coexisting individuals. How does natural selection maintain such diversity within and across populations? A popular theoretical basis for the maintenance of diversity is cyclic dominance, illustrated by the rock-paper-scissor game. However, it appears difficult to find cyclic dominance in nature. Why is this case? Focusing on continuously produced novel mutations, we theoretically addressed the rareness of cyclic dominance. We developed a model of an evolving population and studied the formation of cyclic dominance. Our results showed that the chance for cyclic dominance to emerge is lower when the newly introduced type is similar to existing types, whereas the introduction of an unrelated type improves these chances. This suggests that cyclic dominance is more likely to evolve through the assembly of unrelated types whereas it rarely evolves within a community of similar types.
COVID-19: Viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection
Authors: Messina Francesco , Giombini Emanuela , Agrati Chiara , Vairo Francesco , Bartoli Tommaso Ascoli , Moghazi Samir Al , Piacentini Mauro , Locatelli Franco , Kobinger Gary , Maeurer Markus , Zumla Alimuddin , Capobianchi Maria R. , Lauria Francesco Nicola , Ippolito Giuseppe ,   COVID 19 INMI Network Medicine for IDs Study Group
Published: May 2020

AbstractBackgroundEpidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information.MethodsWe investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis.The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells.ResultsAlthough the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines.ConclusionsIn this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.
Time-dependent discrimination advantages for harmonic sounds suggest efficient coding for memory
Authors: McPherson Malinda J. , McDermott Josh H. 
Published: May 2020

AbstractPerceptual systems have finite memory resources and must store incoming signals in compressed formats. To explore whether representations of a sound’s pitch might derive from this need for compression, we compared discrimination of harmonic and inharmonic sounds across delays. In contrast to inharmonic spectra, harmonic spectra can be summarized, and thus compressed, using their fundamental frequency (f0). Participants heard two sounds and judged which was higher. Despite being comparable for sounds presented back-to-back, discrimination was better for harmonic than inharmonic stimuli when sounds were separated in time, implicating memory representations unique to harmonic sounds. Patterns of individual differences (correlations between thresholds in different conditions) indicated that listeners use different representations depending on the time delay between sounds, directly comparing the spectra of temporally adjacent sounds, but transitioning to comparing f0s across delays. The need to store sound in memory appears to determine reliance on f0-based pitch, and may explain its importance in music, in which listeners must extract relationships between notes separated in time.
Lifestyle adaptations ofRhizobiumfrom rhizosphere to symbiosis
Authors: Wheatley Rachel M. , Ford Brandon L. , Li Li , Aroney Samuel T. N. , Knights Hayley E. , Ledermann Raphael , East Alison K. , Ramachandran Vinoy K. , Poole Philip S. 
Published: May 2020

AbstractBy analyzing successive lifestyle stages of a modelRhizobium-legume symbiosis using mariner-based transposon insertion sequencing (INSeq), we have defined the genes required for rhizosphere growth, root colonization, bacterial infection, N2-fixing bacteroids and release from legume (pea) nodules. While only 27 genes are annotated asnifandfixinRhizobium leguminosarum, we show 603 genetic regions (593 genes, 5 tRNAs and 5 RNA features) are required for the competitive ability to nodulate pea and fix N2. Of these, 146 are common to rhizosphere growth through to bacteroids. This large number of genes, defined as rhizosphere-progressive, highlights how critical successful competition in the rhizosphere is to subsequent infection and nodulation. As expected, there is also a large group (211) specific for nodule bacteria and bacteroid function. Nodule infection and bacteroid formation require genes for motility, cell envelope restructuring, nodulation signalling, N2fixation, and metabolic adaptation. Metabolic adaptation includes urea, erythritol and aldehyde metabolism, glycogen synthesis, dicarboxylate metabolism and glutamine synthesis (GlnII). There are separate lifestyle adaptations specific to rhizosphere growth (17) and root colonization (23), distinct from infection and nodule formation. These results dramatically highlight the importance of competition at multiple stages of aRhizobium-legume symbiosis.SignificanceRhizobia are soil-dwelling bacteria that form symbioses with legumes and provide biologically useable nitrogen as ammonium for the host plant. High-throughput DNA sequencing has led to a rapid expansion in publication of complete genomes for numerous rhizobia, but analysis of gene function increasingly lags gene discovery. Mariner-based transposon insertion sequencing (INSeq) has allowed us to characterize the fitness contribution of bacterial genes and determine those functionally important in aRhizobium-legume symbiosis at multiple stages of development.