bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancestral chromosomes for the Peronosporaceae inferred from a telomere-to-telomere genome assembly of Peronospora effusa
Authors: Fletcher Kyle , Shin Oon-Ha , Clark Kelley J. , Feng Chunda , Putman Alexander I. , Correll James C. , Klosterman Steven J. , Van Deynze Allen , Michelmore Richard 
Published: September 2021

AbstractWe report the first telomere-to-telomere genome assembly for an oomycete. This assembly has extensive synteny with less complete genome assemblies of other oomycetes and will therefore serve as a reference genome for this taxon. Downy mildew disease of spinach, caused by the oomycete Peronospora effusa, causes major losses to spinach production. The 17 chromosomes of P. effusa were assembled telomere-to-telomere using Pacific Biosciences High Fidelity reads. Sixteen chromosomes are complete and gapless; Chromosome 15 contains one gap bridging the nucleolus organizer region. Putative centromeres were identified on all chromosomes. This new assembly enables a re-evaluation of the genomic composition of Peronospora spp.; the assembly was almost double the size and contained more repeat sequences than previously reported for any Peronospora spp. Genome fragments consistently under-represented in six previously reported assemblies of P. effusa typically encoded repeats. Some genes annotated as encoding effectors were organized into multigene clusters on several chromosomes. At least two effector-encoding genes were annotated on every chromosome. The intergenic distances between annotated genes were consistent with the two-speed genome hypothesis, with some effectors located in gene-sparse regions. The near-gapless assembly revealed apparent horizontal gene transfer from Ascomycete fungi. Gene order was highly conserved between P. effusa and the genetically oriented assembly of the oomycete Bremia lactucae. High levels of synteny were also detected with Phytophthora sojae. Many oomycete species may have similar chromosome organization; therefore, this genome assembly provides the foundation for genomic analyses of diverse oomycetes.
Dynamic and stationary brain connectivity during movie watching as revealed by functional MRI
Authors: Di Xin , Zhang Zhiguo , Xu Ting , Biswal Bharat B. 
Published: September 2021

AbstractSpatially remote brain regions show synchronized activity as typically revealed by correlated functional MRI (fMRI) signals. An emerging line of research has focused on the temporal fluctuations of connectivity; however, its relationships with stationary connectivity have not been clearly illustrated. We examined dynamic and stationary connectivity when the participants watched four different movie clips. We calculated point-by-point multiplication between two regional time series to estimate the time-resolved dynamic connectivity, and estimated the inter-individual consistency of the dynamic connectivity time series. Widespread consistent dynamic connectivity was observed for each movie clip, which also showed differences between the clips. For example, a cartoon movie clip, Wall-E, showed more consistent of dynamic connectivity with the posterior cingulate cortex and supramarginal gyrus, while a court drama clip, A Few Good Men, showed more consistent of dynamic connectivity with the auditory cortex and temporoparietal junction, which might suggest the involvement of specific brain processing for different movie contents. In contrast, the stationary connectivity as measured by the correlations between regional time series was highly similar among the movie clips, and showed fewer statistically significant differences. The patterns of consistent dynamic connectivity could be used to classify different movie clips with higher accuracy than the stationary connectivity and regional activity. These results support the functional significance of dynamic connectivity in reflecting functional brain changes, which could provide more functionally relevant information than stationary connectivity.
Naturalistic stimuli reveal a critical period in visual cortex development: Evidence from adult-onset blindness
Authors: Musz Elizabeth , Loiotile Rita , Chen Janice , Cusack Rhodri , Bedny Marina 
Published: September 2021

AbstractHow do life experiences impact cortical function? In people who are born blind, the “visual” cortices are recruited for nonvisual tasks such as Braille reading and sound localization (e.g., Collignon et al., 2011; Sadato et al., 1996). The mechanisms of this recruitment are not known. Do visual cortices have a latent capacity to respond to nonvisual information that is equal throughout the lifespan? Alternatively, is there a sensitive period of heightened plasticity that makes visual cortex repurposing possible during childhood? To gain insight into these questions, we leveraged naturalistic auditory stimuli to quantify and compare cross-modal responses congenitally blind (CB, n=22), adult-onset blind (vision loss >18 years-of-age, AB, n=14) and sighted (n=22) individuals. Participants listened to auditory excerpts from movies; a spoken narrative; and matched meaningless auditory stimuli (i.e., shuffled sentences, backwards speech) during fMRI scanning. These rich naturalistic stimuli made it possible to simultaneous engage a broad range of cognitive domains. We correlated the voxel-wise timecourses of different participants within each group. For all groups, all stimulus conditions induced synchrony in auditory cortex and for all groups only the narrative stimuli synchronized responses in higher-cognitive fronto-parietal and temporal regions. Inter-subject synchrony in visual cortices was high in the CB group for the movie and narrative stimuli but not for meaningless auditory controls. In contrast, visual cortex synchrony was equally low among AB and sighted blindfolded participants. Even many years of blindness in adulthood fail to enable responses to naturalistic auditory information in visual cortices of people who had sight as children. These findings suggest that cross-modal responses in visual cortex of people born blind reflect the plasticity of developing visual cortex during a sensitive period.
A Role for Visual Areas in Physics Simulations
Authors: Ahuja Aarit , Desrochers Theresa M. , Sheinberg David L. 
Published: September 2021

AbstractTo engage with the world, we must regularly make predictions about the outcomes of physical scenes. How do we make these predictions? Recent evidence points to simulation - the idea that we can introspectively manipulate rich, mental models of the world - as one possible explanation for how such predictions are accomplished. While theories based on simulation are supported by computational models, neuroscientific evidence for simulation is lacking and many important questions remain. For instance, do simulations simply entail a series of abstract computations? Or are they supported by sensory representations of the objects that comprise the scene being simulated? We posit the latter and suggest that the process of simulating a sequence of physical interactions is likely to evoke an imagery-like envisioning of those interactions. Using functional magnetic resonance imaging, we demonstrate that when participants predict how a ball will fall through an obstacle-filled display, motion-sensitive brain regions are activated. We further demonstrate that this activity, which occurs even though no motion is being sensed, resembles activity patterns that arise while participants perceive the ball’s motion. This finding suggests that the process of simulating the ball’s movement is accompanied by a sensory representation of this movement. These data thus demonstrate that mental simulations recreate sensory depictions of how a physical scene is likely to unfold.
Defective endosome-TGN retrograde transport promotes NLRP3 inflammasome activation
Authors: Zhang Zhirong , Ran Li , Venditti Rossella , Liu Zengzhen , Schürmann Annette , Bonifacino Juan S. , De Matteis Maria Antonietta , Ricci Romeo 
Published: September 2021

SummaryInflammasome complexes are pivotal in the innate immune response to pathogens and other danger signals1–4. The NLRP3 inflammasome is activated in response to a broad variety of cellular stressors. Most of the stimuli act in a potassium efflux-dependent manner but a primary and converging sensing mechanism by the NLRP3 receptor initiating inflammasome assembly remains ill-defined. Here we show that NLRP3 activators disrupt endosome-TGN retrograde transport (ETRT) and lead to localization of NLRP3 to endosomal vesicles. Genetic and pharmacologic perturbation of ETRT leads to accumulation of phosphoinositol-4-phosphate (PI4P) in endosomes to which NLRP3 is recruited. Disruption of ETRT potentiates NLRP3 inflammasome activation in murine and human macrophages in vitro. Mice with defects in ETRT in the myeloid compartment are more susceptible to LPS-induced sepsis showing enhanced mortality and IL-1β serum levels as compared to control animals. Our study thus uncovers that changes in endocytic trafficking mediate NLRP3-dependent inflammatory responses.
Single cell infection with influenza A virus using drop-based microfluidics
Authors: Loveday Emma Kate , Sanchez Humberto S. , Thomas Mallory M. , Chang Connie B. 
Published: September 2021

SummaryInfluenza A virus (IAV) is an RNA virus with high genetic diversity which necessitates the development of new vaccines targeting emerging mutations each year. As IAV exists in genetically heterogeneous populations, current studies focus on understanding population dynamics at the single cell level. These studies include novel methodology that can be used for probing populations at the single cell level, such as single cell sequencing and microfluidics. Here, we introduce a drop-based microfluidics method to study IAV infection at a single cell level by isolating infected host cells in microscale drops. Single human alveolar basal epithelial (A549), Madin-Darby Canine Kidney cells (MDCK) and MDCK + human siat7e gene (Siat7e) cells infected with the pandemic A/California/07/2009 (H1N1) strain were encapsulated within 50 μm radii drops and incubated at 37°C. We demonstrate that drops remain stable over 24 hours, that 75% of cells remain viable, and that IAV virus can propagate within the drops. Drop-based microfluidics therefore enables single cell analysis of viral populations produced from individually infected cells.
Exploring the effects of CO2elevation on seedlings’ growth of Acacia senegal in the era of changes
Authors: Attaelmanan Abdelmoniem A. , Siddig Ahmed A. H. , Warrag Essam I. 
Published: September 2021

AbstractAcacia senegalis a priority and important C3tree species in drylands of Sudan and across the gum belt. Investigation of its seedlings response to elevated carbon dioxide (eCO2) is important as atmospheric ([CO2]) has increased and predicted to continue to rise. Many studies showed that eCO2causes increased photosynthesis in plants, which leads to greater production of carbohydrates and biomass, and increased soil organic matter and carbon content. This study investigated the effects of eCO2onA. senegalseedlings grown in sand and silt soils under irrigation intervals of every day and every two days. Seven days old seedlings were assigned to the treatments in Split - spilt plot design for 4 weeks. The main plot is eCO2(600-800 ppm) and ambient (≤400 ppm) under Free Air CO2Enrichment (FACE) system. Subplots are irrigation intervals and soil types. Seedling height and number of leaves were measured weekly, and seedlings were harvested after 4 weeks where growth parameters and soil properties were measured. The eCO2showed no effect on the measured parameters except the significant increase in tap-root length. However, the irrigation every day showed significant increase than every two days in seedling’s height, number of leaves, root length and seedling’s dry weight but not seedling’s and soil C% & N%. Soil treatment showed effects on stem height, leaf number, seedling’s dry weight, leaves and root N% and soil C% but not root length, seedling C% and soil N%. The results indicate the importance of soil moisture, physical and chemical properties that reflects adaptation of the species to its dry land environment.
Signatures of adaptive evolution during human to mink SARS CoV2 cross-species transmission inform estimates of the COVID19 pandemic timing
Authors: Tai Jui-Hung , Chaw Shu-Miaw , Sun Hsiao-Yu , Tseng Yi-Cheng , Li Guanghao , Chang Sui-Yuan , Yeh Shiou-Hwei , Chen Pei-Jer , Wang Hurng-Yi 
Published: September 2021

ABSTRACTOne of the unique features of SARS-CoV-2 is that it mainly evolved neutrally or under purifying selection during the early pandemic. This contrasts with the preceding epidemics of the closely related SARS-CoV and MERS-CoV, both of which evolved adaptively. It is possible that the SARS-CoV-2 exhibits a unique or adaptive feature which deviates from other coronaviruses. Alternatively, the virus may have been cryptically circulating in humans for a sufficient time to have acquired adaptive changes for efficient transmission before the onset of the current pandemic. In order to test the above scenarios, we analyzed the SARS-CoV-2 sequences from minks (Neovision vision) and parenteral human strains. In the early phase of the mink epidemic (April to May 2020), nonsynonymous to synonymous mutation ratios per site within the spike protein was 2.93, indicating a selection process favoring adaptive amino acid changes. In addition, mutations within this protein concentrated within its receptor binding domain and receptor binding motif. Positive selection also left a trace on linked neutral variation. An excess of high frequency derived variants produced by genetic hitchhiking was found during middle (June to July 2020) and early late (August to September 2020) phases of the mink epidemic, but quickly diminished in October and November 2020. Strong positive selection found in SARS-CoV-2 from minks implies that the virus may be not unique in super-adapting to a wide range of new hosts. The mink study suggests that SARS-CoV-2 already went through adaptive evolution in humans, and likely been circulating in humans at least six months before the first case found in Wuhan, China. We also discuss circumstances under which the virus can be well-adapted to its host but fail to induce an outbreak.
Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling
Authors: Pezeshkian Weria , Grünewald Fabian , Narykov Oleksandr , Lu Senbao , Arkhipova Valeria , Solodovnikov Alexey , Wassenaar Tsjerk A , Marrink Siewert J. , Korkin Dmitry 
Published: September 2021

AbstractDespite tremendous efforts by the research community during the COVID-19 pandemic, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. Being a key structural component of the SARS-CoV-2 virion, the envelope encapsulates viral RNA and is composed of three structural proteins, spike (S), membrane (M), and envelope (E), which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multiscale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns formed by M’s transmembrane and intravirion (endo) domains. These results are in good agreement with current experimental data, demonstrating a generic and versatile integrative approach to model the structure of a virus de novo. We anticipate our work to provide insights into critical roles of structural proteins in the viral assembly and integration, proposing new targets for the antiviral therapies.
Droplet-based Single-cell Total RNA-seq Reveals Differential Non-Coding Expression and Splicing Patterns during Mouse Development
Authors: Salmen Fredrik , De Jonghe Joachim , Kaminski Tomasz S. , Alemany Anna , Parada Guillermo , Verity-Legg Joe , Yanagida Ayaka , Kohler Timo N. , Battich Nicholas , van den Brekel Floris , Ellermann Anna L. , Arias Alfonso Martinez , Nichols Jennifer , Hemberg Martin , Hollfelder Florian , van Oudenaarden Alexander 
Published: September 2021

ABSTRACTIn recent years, single-cell transcriptome sequencing has revolutionized biology, allowing for the unbiased characterization of cellular subpopulations. However, most methods amplify the termini of polyadenylated transcripts capturing only a small fraction of the total cellular transcriptome. This precludes the detection of many long non-coding, short non-coding and non-polyadenylated protein-coding transcripts. Additionally, most workflows do not sequence the full transcript hindering the analysis of alternative splicing. We therefore developed VASA-seq to detect the total transcriptome in single cells. VASA-seq is compatible with both plate-based formats and droplet microfluidics. We applied VASA-seq to over 30,000 single cells in the developing mouse embryo during gastrulation and early organogenesis. The dynamics of the total single-cell transcriptome result in the discovery of novel cell type markers many based on non-coding RNA, an in vivo cell cycle analysis and an improved RNA velocity characterization. Moreover, it provides the first comprehensive analysis of alternative splicing during mammalian development.
Dynamic behavior of cell-free mitochondrial DNA in human saliva
Authors: Trumpff Caroline , Rausser Shannon , Haahr Rachel , Karan Kalpita R. , Gouspillou Gilles , Puterman Eli , Kirschbaum Clemens , Picard Martin 
Published: September 2021

AbstractMitochondria contain their own genome that can be released in multiple biofluids such as blood and cerebrospinal fluid, as cell-free mitochondrial DNA (cf-mtDNA). In clinical studies, single measures of blood cf-mtDNA predict mortality, and higher cf-mtDNA levels are associated with mental and physical stress. However, the dynamics of cf-mtDNA has not been defined, and whether it can be measured non-invasively like other neuroendocrine markers in saliva has not been examined. Here we report cf-mtDNA in human saliva and establish its natural within-person dynamic behavior across multiple weeks. In a small proof-of-principle cohort of healthy adults, we first develop an approach to rapidly quantify salivary cf-mtDNA without DNA extraction, and demonstrate the existence of saliva cf-mtDNA. We then deploy this approach to perform an intensive repeated-measures analysis of two healthy men studied at 4 daily timepoints over 53-60 consecutive days (n=212-220 observations each) with parallel measures of steroid hormones, self-reported daily mood, and health-related behaviors. Salivary cf-mtDNA exhibited a robust awakening response reaching up to two orders of magnitude 30-45 minutes after awakening, varied from day-to-day, and moderately correlated with the cortisol awakening response. No consistent association with self-reported daily mood/health-related behaviors were found, although this requires further examination in more extensive studies. Dynamic variation in cf-mtDNA was inversely related with salivary interleukin 6 (IL6), inconsistent with a pro-inflammatory effect of salivary cf-mtDNA. The highly dynamic behavior of salivary cf-mtDNA opens the door to non-invasive studies examining the relevance of mtDNA signaling in relation to human health.
Integrated gene analyses ofde novomutations from 46,612 trios with autism and developmental disorders
Authors: Wang Tianyun , Kim Chang , Bakken Trygve E. , Gillentine Madelyn A. , Henning Barbara , Mao Yafei , Gilissen Christian ,   The SPARK Consortium, Nowakowski Tomasz J. , Eichler Evan E. 
Published: September 2021

ABSTRACTMost genetic studies consider autism spectrum disorder (ASD) and developmental disorder (DD) separately despite overwhelming comorbidity and shared genetic etiology. Here we analyzedde novomutations (DNMs) from 15,560 ASD (6,557 are new) and 31,052 DD trios independently and combined as broader neurodevelopmental disorders (NDD) using three models. We identify 615 candidate genes (FDR 5%, 189 potentially novel) by one or more models, including 138 reaching exome-wide significance (p < 3.64e-07) in all models. We find no evidence for ASD-specific genes in contrast to 18 genes significantly enriched for DD. There are 53 genes show particular mutational-bias including enrichments for missense (n=41) or truncating DNM (n=12). We find 22 genes with evidence of sex-bias including five X chromosome genes also with significant female burden (DDX3X, MECP2, SMC1A, WDR45, andHDAC8). NDD risk genes group into five functional networks associating with different brain developmental lineages based on single-cell nuclei transcriptomic data, which provides important insights into disease subtypes and future functional studies.
Construction of a solid Cox model for AML patients based on multiomics bioinformatic analysis
Authors: Li Fu , Cai Jiao , Liu Jia , Yu Shi-cang , Zhang Xi , Su Yi , Gao Lei 
Published: September 2021

AbstractAcute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. The bone marrow (BM) microenvironment in AML plays an important role in leukemogenesis, drug resistance and leukemia relapse. In this study, we aimed to identify reliable immune-related biomarkers for AML prognosis by multiomics analysis. We obtained expression profiles from The Cancer Genome Atlas (TCGA) database and constructed a LASSO-Cox regression model to predict the prognosis of AML using multiomics bioinformatic analysis data. This was followed by independent validation of the model in the GSE106291 (n=251), GSE12417 (n=163) and GSE37642 (n=137) datasets and mutated genes in clinical samples for predicting overall survival (OS). Molecular docking was performed to predict the most optimal ligands to these hub genes. The single-cell RNA sequence dataset GSE116256 was used to clarify the expression of the hub genes in different immune cell types. According to their significant differences in immune gene signatures and survival trends, we concluded that the immune infiltration-lacking subtype (IL type) is associated with better prognosis than the immune infiltration-rich subtype (IR type). Using the LASSO model, we built a classifier based on 5 hub genes to predict the prognosis of AML (risk score = −0.086×ADAMTS3 + 0.180×CD52 + 0.472×CLCN5 - 0.356×HAL + 0.368×ICAM3). In summary, we constructed a prognostic model of AML using integrated multiomics bioinformatic analysis that could serve as a therapeutic classifier.