bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light induced changes in starry flounder (Platichthys stellatus) opsin expression and its influence on vision estimated from a camouflage-based behavioural assay
Authors: Iwanicki Tom , Haman Cliff , Liu Amy , Taylor John S. 
Published: July 2020

AbstractCorrelations between variation in opsin expression and variation in vision are often assumed but rarely tested. We exposed starry flounder (Platichthys stellatus) to either broad spectrum sunlight or green-filtered light in outdoor aquaria for seven weeks and then combined digital-PCR and camouflage experiments to test two hypotheses: i) short-wavelength sensitive opsin expression decreases in a green light environment, and ii) if observed, this change in opsin expression influences colour vision as estimated using a camouflage-based behavioural assay. Of the eight visual opsins measured,Sws1(UV sensitive) andSws2B(blue sensitive) expression was significantly lower in fish exposed to green light. However, opsin expression in fish transferred to an arena illuminated with white LED light for three hours after the green light treatment did not differ from broad spectrum controls. Changes in opsin expression in response to artificial light environments have been reported before, but rapid changes over three hours rather than days or weeks is unprecedented. We did not observe a significant difference in a flounder’s camouflage response based on light environment, although broad spectrum fish increased and green-filter fish decreased the pattern contrast when on the blue-green substrate, and this difference approached significance. This pattern is intriguing considering green-filter fish expressed fewer UV and blue opsins and we recommend increased statistical power for future experiments. Together, our results show that starry flounder opsin expression changes rapidly in response to changes in light environment, however, there is no apparent effect on their visually mediated camouflage.
Perception of and anxiety about COVID-19 infection and risk behaviors for spreading infection: An international comparison
Authors: Shiina Akihiro , Niitsu Tomihisa , Kobori Osamu , Idemoto Keita , Hashimoto Tasuku , Sasaki Tsuyoshi , Igarashi Yoshito , Shimizu Eiji , Nakazato Michiko , Hashimoto Kenji , Iyo Masaomi 
Published: July 2020

AbstractTo control the spread of the newly developed corona viral infection diseases (COVID-19), people’s appropriate precautionary behaviors should be promoted. We conducted a series of online questionnaire survey, to gather a total of 8,000 citizen’s responses on March 27–28, 2020 in Japan and April 17–21 in the UK and Spain. Compared to Japan, the knowledge and anxiety level and the frequency of precautionary behaviors were higher in the UK and Spain. Participants with infected acquaintances were more concerned about COVID-19. However, participants in the UK rarely wore a medical mask. Participants in the UK and Spain were eager to get information about COVID-19 compared to those in Japan. The participants in Spain tended not to trust official information and to believe specialists' comments instead. The urgency of the spread of COVID-19, cultural backgrounds, and recent political situations appear to contribute to the differences among countries revealed herein.
Epigenetic suppression of SLFN11 in germinal center B cells in the process of the dynamic expression change during B-cell development
Authors: Moribe Fumiya , Nishikori Momoko , Sasanuma Hiroyuki , Akagawa Remi , Arima Hiroshi , Takeda Shunichi , Takaori-Kondo Akifumi , Murai Junko 
Published: July 2020

ABSTRACTBackgroundSLFN11 enhances cellular toxicity of genotoxic anti-cancer agents, and its important role under physiological conditions has not been appreciated yet. Somatic hypermutations and class switch recombination that can cause physiological genotoxic stress arise in germinal center B cells (GCBs). GCBs are a major origin of B-cell lymphomas that are frequently treated by cytosine arabinoside, a genotoxic anti-cancer agent.ObjectiveTo clarify the expression profile ofSLFN11in different stages of B cells and B-cell lymphomas.MethodsWe analyzed the expression ofSLFN11by mining publicly available databases for different stages of normal B cells and various types of B-cell lymphoma lines and also by performing immunohistochemical staining of human lymph nodes. We investigated the effects of two epigenetic modifiers, an EZH2 inhibitor, tazemetostat (EPZ6438) and a histone deacetylase inhibitor, panobinostat (LBH589) onSLFN11expression in B-cell lymphoma lines and examined the therapeutic efficacy of these epigenetic modifiers in the combination with cytosine arabinoside.ResultsSLFN11expression was specifically low in GCBs compared to non-GCBs, which was consolidated by the immunohistochemical staining for SLFN11 with human lymph nodes.SLFN11expression levels in B-cell lymphoma lines largely correlated to those of their normal counterparts. The epigenetic modifiers upregulatedSLFN11expression in GCB-derived lymphomas and made the lymphomas further susceptible to cytosine arabinoside.ConclusionsThe expression ofSLFN11may be epigenetically suppressed in GCBs and GCB-derived lymphomas. GCB-derived lymphomas with lowSLFN11expression can be treated by the combination of epigenetic modifiers and cytosine arabinoside.
Increases in whole brain grey matter associated with long-term Sahaja Yoga Meditation: a detailed area by area description
Authors: Hernández Sergio Elías , Dorta Roberto , Suero José , Barros-Loscertales Alfonso , González-Mora José Luis , Rubia Katya 
Published: July 2020

AbstractObjectivesOur previous study showed that long-term practitioners of Sahaja Yoga Meditation (SYM) had around 7% larger grey matter volume (GMV) in the whole brain compared with healthy controls; however, when testing individual regions, only 5 small brain areas were statistically different between groups. Under the hypothesis that those results were statistically conservative, with the same dataset, we investigated in more detail the regional differences in GMV associated with the practice of SYM, with a different statistical approach.DesignTwenty-three experienced practitioners of SYM and 23 healthy non-meditators matched on age, gender and education level, were scanned using structural Magnetic Resonance Imaging. Their GMV were extracted and compared using Voxel-Based Morphometry. Using a novel ad-hoc GLM model, statistical comparisons were made to observe if the GMV differences between meditators and controls were statistically significant.ResultsIn the 16 lobe area subdivisions, GMV was statistically significantly different in 4 out of 16 areas: Right hemispheric temporal and frontal lobes, left frontal lobe and brainstem.In the 116 AAL area subdivisions, GMV difference was statistically significant in 11 areas. The GMV differences were statistically more significant in right hemispheric brain areas.ConclusionsThe study shows that long-term practice of SYM is associated with larger GMV overall, and with significant differences mainly in temporal and frontal areas of the right hemisphere and the brainstem. These neuroplastic changes may reflect emotional and attentional control mechanisms developed with SYM. On the other hand, our statistical ad-hoc method shows that there were more brain areas with statistical significance compared to the traditional methodology which we think is susceptible to conservative Type II errors.
EUAdb: a resource for COVID-19 test development
Authors: Woronik Alyssa , Shaffer Henry W. , Kiontke Karin , Laurent Jon M. , Zambrano Ronald , Boeke Jef D. , Fitch David H. A. 
Published: July 2020

AbstractDue to the sheer number of COVID-19 (coronavirus disease 2019) cases, the prevalence of asymptomatic cases and the fact that undocumented cases appear to be significant for transmission of the causal virus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), there is an urgent need for increased SARS-CoV-2 testing capability that is both efficient and effective1. In response to the growing threat of the COVID-19 pandemic in February, 2020, the FDA (US Food and Drug Administration) began issuing Emergency Use Authorizations (EUAs) to laboratories and commercial manufacturers for the development and implementation of diagnostic tests1. So far, the gold standard assay for SARS-CoV-2 detection is the RT-qPCR (real-time quantitative polymerase chain reaction) test2. However, the authorized RT-qPCR test protocols vary widely, not only in the reagents, controls, and instruments they use, but also in the SARS-CoV-2 genes they target, what results constitute a positive SARS-CoV-2 infection, and their limit of detection (LoD). The FDA has provided a web site that lists most of the tests that have been issued EUAs, along with links to the authorization letters and summary documents describing these tests1. However, it is very challenging to use this site to compare or replicate these tests for a variety of reasons. First, at least 12 of 18 tests for EUA submissions made prior to March 31, 2020, are not listed there. To our knowledge, no EUAs have been issued for these applications. Second, the data are not standardized and are only provided as longhand prose in the summary documents. Third, some details (e.g. primer sequences) are absent from several of the test descriptions. Fourth, for tests provided by commercial manufacturers, summary documents are completely missing. To address at least the first three issues, we have developed a database, EUAdb (EUAdb.org), that holds standardized information about EUA-issued tests and is focused on RT-qPCR diagnostic tests, or “high complexity molecular-based laboratory developed tests”1. By providing a standardized ontology and curated data in a relational architecture, we seek to facilitate comparability and reproducibility, with the ultimate goal of consistent, universal and high-quality testing nationwide. Here, we document the basics of the EUAdb data architecture and simple data queries. The source files can be provided to anyone who wants to modify the database for his/her own research purposes. We ask that the original source of the files be made clear and that the database not be used in its original or modified forms for commercial purposes.
Glycine Rich Segments Adopt Polyproline II Helices Which May Contribute to Biomolecular Condensate Formation
Authors: Mompeán Miguel , McAvan Bethan S. , Félix Sara S. , Treviño Miguel , Oroz Javier , Pantoja-Uceda David , Cabrita Eurico J. , Doig Andrew J. , Laurents Douglas V. 
Published: July 2020

AbstractMany intrinsically disordered proteins contain Gly-rich regions which are generally assumed to be disordered. Such regions often form biomolecular condensates which play essential roles in organizing cellular processes. However, the bases of their formation and stability are still not completely understood. Considering NMR studies of the Gly-richH. harveyi“snow flea” antifreeze protein, we recently proposed that Gly-rich sequences, such as the third “RGG” region of Fused in Sarcoma (FUS) protein, may adopt polyproline II helices whose association might stabilize condensates. Here, this hypothesis is tested with a polypeptide corresponding to the third RGG region of FUS. NMR spectroscopy and molecular dynamics simulations suggest that significant populations of polyproline II helix are present. These findings are corroborated in a model peptide Ac-RGGYGGRGGWGGRGGY-NH2, where a peak characteristic of polyproline II helix is observed using CD spectroscopy. Its intensity suggests a polyproline II population of 40%. This result is supported by data from FTIR and NMR spectroscopies. In the latter, NOE correlations are observed between the Tyr and Arg, and Arg and Trp side chain hydrogens, confirming that side chains spaced three residues apart are close in space. Taken together, the data are consistent with a polyproline II helix, which is bent to optimize interactions between guanidinium and aromatic moieties, in equilibrium with a statistical coil ensemble. In cells, the polyproline II population of these peptides could be augmented by binding profilin protein or SH3, WW or OCRE domains, association with RNA or assembly into polyproline II helical bundles. These results lend credence to the hypothesis that Gly-rich segments of disordered proteins may form polyproline II helices which help stabilize biomolecular condensates.
Genetic signatures for lineage/sublineage classification of HPV16, 18, 52 and 58 variants
Authors: Ou Zhihua , Chen Zigui , Zhao Yanping , Lu Haorong , Liu Wei , Li Wangsheng , Geng Chunyu , Hu Guohai , Wang Xiaman , Ren Peidi , Liu Na , Zhu Shida , Lu Ling , Li Junhua 
Published: July 2020

AbstractIncreasing evidences indicate that high-risk HPV variants are heterogeneous in carcinogenicity and ethnic dispersion. In this work, we identified genetic signatures for convenient determination of lineage/sublineage of HPV16, 18, 52 and 58 variants. Using publicly available genomes, we found that E2 of HPV16, L2 of HPV18, L1 and LCR of HPV52, and L2, LCR and E1 of HPV58 contain the proper genetic signature for lineage/sublineage classification. Sets of hierarchical signature nucleotide positions (SNPs) were further confirmed for high accuracy (>98%) by classifying HPV genomes obtained from Chinese females, which included 117 HPV16 variants, 48 HPV18 variants 117 HPV52 variants and 89 HPV58 variants. The circulation of HPV variants posing higher cancer risk in Eastern China, such as HPV16 A4 and HPV58 A3, calls for continuous surveillance in this region. The marker genes and signature nucleotide positions may facilitate cost-effective diagnostic detections of HPV variants in clinical settings.
A dynamic regulatory interface on SARS-CoV-2 RNA polymerase
Authors: Shi Wei , Chen Ming , Yang Yang , Zhou Wei , Chen Shiyun , Yang Yi , Hu Yangbo , Liu Bin 
Published: July 2020

AbstractThe RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is the core machinery responsible for the viral genome replication and transcription and also a major antiviral target. Here we report the cryo-electron microscopy structure of a post-translocated SARS-CoV-2 RdRp core complex, comprising one nsp12, one separate nsp8(I) monomer, one nsp7-nsp8(II) subcomplex and a replicating RNA substrate. Compared with the recently reported SARS-CoV-2 RdRp complexes, the nsp8(I)/nsp7 interface in this RdRp complex shifts away from the nsp12 polymerase. Further functional characterizations suggest that specific interactions between the nsp8(I) and nsp7, together with the rearrangement of nsp8(I)/nsp7 interface, ensure the efficient and processive RNA synthesis by the RdRp complex. Our findings provide a mechanistic insight into how nsp7 and nsp8 cofactors regulate the polymerase activity of nsp12 and suggest a potential new intervention interface, in addition to the canonical polymerase active center, in RdRp for antiviral design.Author summarySince it was first discovered and reported in late 2019, the coronavirus disease 2019 (COVID-19) pandemic caused by highly contagious SARS-CoV-2 virus is wreaking havoc around the world. Currently, no highly effective and specific antiviral drug is available for clinical treatment. Therefore, the threat of COVID-19 transmission necessitates the discovery of more effective antiviral strategies. Viral RNA-dependent RNA polymerase (RdRp) is an important antiviral drug target. Here, our cryo-EM structure of a SARS-CoV-2 RdRp/RNA replicating complex reveals a previously uncharacterized overall shift of the cofactor nsp8(I)/nsp7 interface, leading to its rearrangement. Throughin vitrofunctional test, we found that the specific interactions on the interface are important to the efficient RNA polymerase activity of SARS-CoV-2 RdRp. These observations let us to suggest this interface as a potential new drug intervention site, outside of the canonical polymerase active center, in RdRp for antiviral design. Our findings would provide new insights into regulatory mechanism of this novel SARS-CoV-2 RdRp, contribute to the design of antiviral drugs against SARS-CoV-2, and benefit the global public health.
Inference of population genetic parameters from the continuously serial-sampled sequences of human seasonal influenza A/H3N2
Authors: Croze Myriam , Kim Yuseob 
Published: July 2020

ABSTRACTBasic summary statistics that quantify the population genetic structure of influenza virus are important for understanding and inferring the evolutionary and epidemiological processes. However, global virus sequences were sampled continuously over several decades, scattered semi-randomly over time. This temporal structure of samples and the small effective size of viral population make it difficult to use conventional methods to calculate summary statistics. Here we define statistics that overcome this problem by correcting for sampling time difference in quantifying a pairwise sequence difference. A simple method of linear regression jointly estimates the mutation rate and the level of sequence polymorphism, thus providing the estimate of the effective population size. It also leads to the definition of Wright’sFSTfor arbitrary time-series data. In addition, as an alternative to Tajima’sDstatistic or site frequency spectrum, mismatch distribution corrected for sampling time differences can be obtained and compared between actual and simulated data. Application of these methods to seasonal influenza A/H3N2 viruses sampled between 1980 and 2017 and sequences simulated under the model of recurrent positive selection with meta-population dynamics allowed us to estimate the synonymous mutation rate and find parameter values of selection and demographic structure that fit the observation. We found that the mutation rates of HA and PB1 segments before 2007 were particularly high, and that adding recurrent positive selection in our model was essential for the genealogical structure of the HA segment. Methods developed here can be generally applied to population genetic inferences using serially sampled genetic data.
Heritability of individualized cortical network topography
Authors: Anderson Kevin M. , Ge Tian , Kong Ru , Patrick Lauren M. , Spreng R. Nathan , Sabuncu Mert R. , Thomas Yeo B.T. , Holmes Avram J. 
Published: July 2020

AbstractHuman cortex is patterned by a complex and interdigitated web of large-scale functional networks. Recent methodological breakthroughs reveal variation in the size, shape, and spatial topography of cortical networks across individuals. While spatial network organization emerges across development, is stable over time, and predictive of behavior, it is not yet clear to what extent genetic factors underlie inter-individual differences in network topography. Here, leveraging a novel non-linear multi-dimensional estimation of heritability, we provide evidence that individual variability in the size and topographic organization of cortical networks are under genetic control. Using twin and family data from the Human Connectome Project (n=1,023), we find increased variability and reduced heritability in the size of heteromodal association networks (h2: M=0.33, SD=0.071), relative to unimodal sensory/motor cortex (h2: M=0.44, SD=0.051). We then demonstrate that the spatial layout of cortical networks is influenced by genetics, using our multi-dimensional estimation of heritability (h2-multi; M=0.14, SD=0.015). However, topographic heritability did not differ between heteromodal and unimodal networks. Genetic factors had a regionally variable influence on brain organization, such that the heritability of network topography was greatest in prefrontal, precuneus, and posterior parietal cortex. Taken together, these data are consistent with relaxed genetic control of association cortices relative to primary sensory/motor regions, and have implications for understanding population-level variability in brain functioning, guiding both individualized prediction and the interpretation of analyses that integrate genetics and neuroimaging.SignificanceThe widespread use of population-average cortical parcellations has provided important insights into broad properties of human brain organization. However, the size, location, and spatial arrangement of regions comprising functional brain networks can vary substantially across individuals. Here, we demonstrate considerable heritability in both the size and spatial organization of individual-specific network topography across cortex. Genetic factors had a regionally variable influence on brain organization, such that heritability in network size, but not topography, was greater in unimodal relative to heteromodal cortices. These data suggest individual-specific network parcellations may provide an avenue to understand the genetic basis of variation in human cognition and behavior.
Computational Properties of the Visual Microcircuit
Authors: Hahn Gerald , Kumar Arvind , Schmidt Helmut , Knösche Thomas R. , Deco Gustavo 
Published: July 2020

AbstractThe neocortex is organized around layered microcircuits consisting of a variety of excitatory and inhibitory neuronal types which perform rate-and oscillation based computations. Using modeling, we show that both superficial and deep layers of the primary mouse visual cortex implement two ultrasensitive and bistable switches built on mutual inhibitory connectivity motives between SST, PV and VIP cells. The switches toggle pyramidal neurons between high and low firing rate states that are synchronized across layers through translaminar connectivity. Moreover, inhibited and disinhibited states are characterized by low- and high frequency oscillations, respectively, with layer-specific differences in frequency and power which show asymmetric changes during state transitions. These findings are consistent with a number of experimental observations and embed firing rate together with oscillatory changes within a switch interpretation of the microcircuit.
Small-hairpin RNAs cause target-independent microRNA dysregulation in neurons and elicit global transcriptomic changes
Authors: Kohen Rafi , Baldwin Katherine T. , Garay Patricia M. , Tsukahara Takao , Chen Alex , Flynn Corey G. , Johnson Craig , Zhao Xiao-Feng , Sutton Michael A. , Iwase Shigeki , Giger Roman J. 
Published: July 2020

SUMMARYSmall hairpin RNAs (shRNAs) allow highly efficient gene knockdown. Here we employed different shRNAs to knock down the reticulon RTN4A/NogoA in primary neurons. Depletion of NogoA correlates with altered synaptic protein composition and spontaneous neurotransmission. However, similar phenotypes are not observed upon genetic deletion ofNogoor its receptors. Step-wise introduction of mismatches in the seed region of shNogoA provides further evidence that synaptic phenotypes are NogoA-independent. RNA sequencing revealed global changes in the neuronal transcriptome of cultures transduced with the original shNogoA or closely related variants. Transcriptomic changes are shRNA seed sequence dependent, but not target-specific. Parallel sequencing of small non-coding RNAs revealed dysregulation of microRNAs. Computational analysis shows that the altered miRNA composition correlates with changes in mRNA expression and preferentially affects protein-protein networks that function at synapses. Thus, off-target effects associated with shRNAs are an inherent property, and in particular, altered miRNA composition needs careful consideration.