bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wastewater-based epidemiology for tracking COVID-19 trend and variants of concern in Ohio, United States
Authors: Ai Yuehan , Davis Angela , Jones Danial , Lemeshow Stanley , Tu Huolin , He Fan , Ru Peng , Pan Xiaokang , Bohrerova Zuzana , Lee Jiyoung 
Published: June 2021

AbstractThe global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 129 million confirm cases. Many health authorities around the world have implemented wastewater-based epidemiology as a rapid and complementary tool for the COVID-19 surveillance system and more recently for variants of concern emergence tracking. In this study, three SARS-CoV-2 target genes (N1, N2, and E) were quantified from wastewater influent samples (n = 250) obtained from the capital city and 7 other cities in various size in central Ohio from July 2020 to January 2021. To determine human-specific fecal strength in wastewater samples more accurately, two human fecal viruses (PMMoV and crAssphage) were quantified to normalize the SARS-CoV-2 gene concentrations in wastewater. To estimate the trend of new case numbers from SARS-CoV-2 gene levels, different statistical models were built and evaluated. From the longitudinal data, SARS-CoV-2 gene concentrations in wastewater strongly correlated with daily new confirmed COVID-19 cases (average Spearman’s r = 0.70, p < 0.05), with the N2 gene being the best predictor of the trend of confirmed cases. Moreover, average daily case numbers can help reduce the noise and variation from the clinical data. Among the models tested, the quadratic polynomial model performed best in correlating and predicting COVID-19 cases from the wastewater surveillance data, which can be used to track the effectiveness of vaccination in the later stage of the pandemic. Interestingly, neither of the normalization methods using PMMoV or crAssphage significantly enhanced the correlation with new case numbers, nor improved the estimation models. Whole-genome sequencing result showed that those detected SARS-CoV-2 variants of concern from the wastewater matched with the clinical isolates from the communities. The findings from this study suggest that wastewater surveillance is effective in COVID-19 trend tracking and variant emergence and transmission within a community.
The impact of COVID-19 pandemic on influenza transmission: molecular and epidemiological evidence
Authors: Tran Leon King , Huang Dai-Wei , Li Nien-Kung , Li Lucy M. , Palacios Julia A. , Chang Hsiao-Han 
Published: June 2021

AbstractTo quantify the impact of COVID-19-related control measures on the spread of human influenza virus, we analyzed case numbers, viral molecular sequences, personal behavior data, and policy stringency data from various countries, and found consistent evidence of decrease in influenza incidence after the emergence of COVID-19.Article SummaryWe quantify a noticeable decrease in H1N1 and H3N2 cases and genetic diversity in selected countries since the onset of the COVID-19 pandemic.
Endosperm evolution by duplicated and neofunctionalized Type I MADS-box transcription factors
Authors: Qiu Yichun , Köhler Claudia 
Published: June 2021

AbstractMADS-box transcription factors (TFs) are present in nearly all major eukaryotic groups. They are divided into Type I and Type II that differ in domain structure, functional roles, and rates of evolution. In flowering plants, major evolutionary innovations like flowers, ovules and fruits have been closely connected to Type II MADS-box TFs. The role of Type I MADS-box TFs in angiosperm evolution remains to be identified. Here, we show that the formation of angiosperm-specific Type I MADS-box clades of Mγ and Mγ-interacting Mα genes (Mα*) can be tracked back to the ancestor of all angiosperms. Angiosperm-specific Mγ and Mα* genes were preferentially expressed in the endosperm, consistent with their proposed function as heterodimers in the angiosperm-specific embryo-nourishing endosperm tissue. We propose that duplication and diversification of Type I MADS-genes underpins the evolution of the endosperm, a developmental innovation closely connected to the origin and success of angiosperms.
Measuring Mitochondrial Electron Transfer Complexes in Previously Frozen Cardiac Tissue from the Offspring of Sow: A Model to Assess Exercise-Induced Mitochondrial Bioenergetics Changes
Authors: Barrera Daniel , Upton Sierra , Rauch Megan , Notarianni Tara , Eum Ki Suk , Liberty Megan , Sah Sarmila Venkoba , Liu Robert , Newcomer Sean , May Linda E. , Agbas Emre , Sage Jessica , Kosa Edina , Agbas Abdulbaki 
Published: June 2021

ABSTRACTMeasuring the mitochondrial electron transfer complex (ETC) profile from previously frozen heart tissue samples from offspring born to an exercised sow provided descriptive data about exercise-induced mitochondrial biochemical changes in heart tissue from the offspring born to the exercised sow. The hypothesis proposed and tested was that a regular maternal exercise of a sow during pregnancy would increase the mitochondrial efficiency of offspring heart bioenergetics. This hypothesis was tested by isolating mitochondria using a mild-isolation procedure to assess mitochondrial ETC and supercomplex profiles. The procedure described here allowed for the processing of previously frozen archived heart tissues and eliminated the necessity of fresh mitochondria preparation for the assessment of mitochondrial ETC complexes, supercomplexes, and ETC complex activity profiles. This protocol describes the optimal ETC protein complex measurement in multiplexed antibody-based immunoblotting and super complex assessment using blue-native gel electrophoresis.SUMMARYPreparation of mitochondria-enriched samples from previously frozen archived solid tissues allowed the investigators to perform both functional and analytical assessments of mitochondria in various experimental modalities. This study demonstrates how to prepare mitochondria-enriched preparations from frozen heart tissue and perform analytical assessments of mitochondria.
Transcriptomics of developing wild sunflower seeds from the extreme ends of a latitudinal gradient differing in seed oil composition
Authors: Barnhart Max H. , McAssey Edward V. , Dittmar Emily L. , Burke John M. 
Published: June 2021

AbstractSeed oil composition, an important agronomic trait in cultivated sunflower, varies latitudinally across the native range of its wild progenitor. This pattern is thought to be driven by selection for a higher proportion of saturated fatty acids in southern populations compared to northern populations, likely due to the different temperatures experienced during seed germination. To investigate whether these differences in fatty acid composition between northern and southern populations correspond to transcriptional variation in the expression of genes involved in fatty acid metabolism, we sequenced RNA from developing seeds of sunflowers from Texas, USA and Saskatchewan, Canada (the extreme ends of sunflower’s latitudinal range) grown in a common garden. Over 4,000 genes were found to be differentially expressed between Texas and Canada, including several genes involved in lipid metabolism. Many differentially expressed oil metabolism genes colocalized with known oil QTL. The genes producing stearoyl-ACP-desaturases (SAD) were of particular interest because of their known role in the conversion of fully saturated into unsaturated fatty acids. Two SAD genes were more highly expressed in seeds from Canadian populations, consistent with the observation of increased levels of unsaturated fatty acids in seeds from that region. We also constructed a gene co-expression network to investigate regional variation in network modules. The results of this analysis revealed regional differentiation for eight of twelve modules, but no clear relationship with oil biosynthesis. Overall, the differential expression of SAD genes offers a partial explanation for the observed differences in seed oil composition between Texas and Canada, while the expression patterns of other metabolic genes suggest complex regulation of fatty acid production and usage across latitudes.
Multi-domain touchscreen-based cognitive assessment of C57BL/6J female mice shows whole body exposure to56Fe particle space radiation in maturity improves discrimination learning yet impairs stimulus-response habit learning
Authors: Soler Ivan , Yun Sanghee , Reynolds Ryan P. , Whoolery Cody W. , Tran Fionya H. , Kumar Priya L. , Rong Yuying , DeSalle Matthew J. , Gibson Adam D. , Stowe Ann M. , Kiffer Fred C. , Eisch Amelia J. 
Published: June 2021

AbstractAstronauts during interplanetary missions will be exposed to galactic cosmic radiation, including charged particles like56Fe. Preclinical studies with mature, “astronaut-aged” rodents suggest space radiation diminishes performance in classical hippocampal- and prefrontal cortex-dependent tasks. However, a rodent cognitive touchscreen battery unexpectedly revealed56Fe radiation improves the performance of C57BL/6J male mice in a hippocampal-dependent task (discrimination learning) without changing performance in a striatal-dependent task (rule-based learning). As other preclinical work suggests the female rodent brain may be relatively resistant to charged particle-induced injury, and as the proportion of female vs. male astronauts is increasing, further study on how charged particles influence the touchscreen cognitive performance of female mice is warranted. We hypothesized that, similar to mature male mice, mature female C57BL/6J mice exposed to whole-body56Fe irradiation (3 × 6.7cGy56Fe over 5 days, 600MeV/n) would improve performance vs.Sham conditions in touchscreen tasks relevant to hippocampal and prefrontal cortical function (e.g. location discrimination reversal [LDR] and extinction, respectively). In LDR,56Fe female mice more accurately discriminated two discrete conditioned stimuli relative to Sham mice, suggesting improved hippocampal function. However,56Fe and Sham female mice acquired a new simple stimulus-response behavior and extinguished this acquired behavior at similar rates, suggesting similar prefrontal cortical function. Based on prior work on multiple memory systems, we next tested whether improved hippocampal-dependent function (discrimination learning) came at the expense of striatal rule-based learning (visuomotor conditional learning). Interestingly,56Fe female mice took more days to reach criteria in this striatal-dependent rule-based test relative to Sham mice. Together, our data support the idea of competition between memory systems, as an56Fe-induced decrease in striatal-based learning is associated with enhanced hippocampal-based learning. These data emphasize the power of using a touchscreen-based battery to advance our understanding of the effects of space radiation on mission critical cognitive function in females, and underscore the importance of preclinical space radiation risk studies measuring multiple cognitive processes, thereby preventing NASA’s risk assessments from being based on a single cognitive domain.
Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine
Authors: Pitcovski Jacob , Gruzdev Nady , Abzach Anna , Katz Chen , Ben-Adiva Ran , Schwartz Michal Brand , Yadid Itamar , Haviv Hadar , Rapoport Irena , Bloch Itai , Shadmon Roy , Eitan Zohar , Eliahu Dalia , Hilel Talia , Laster Morris , Tal Sigal Kremer , Tennenbaum Tamara Byk , Shahar Ehud 
Published: June 2021

AbstractThe rapid spread of the COVID-19 pandemic, with its devastating medical and economic impacts, triggered an unprecedented race toward development of effective vaccines. The commercialized vaccines are parenterally administered, which poses logistic challenges, while adequate protection at the mucosal sites of virus entry is questionable. Furthermore, essentially all vaccine candidates target the viral spike (S) protein, a surface protein that undergoes significant antigenic drift. This work aimed to develop an oral multi-antigen SARS-CoV-2 vaccine comprised of the receptor binding domain (RBD) of the viral S protein, two domains of the viral nucleocapsid protein (N), and heat-labile enterotoxin B (LTB), a potent mucosal adjuvant. The humoral, mucosal and cell-mediated immune responses of both a three-dose vaccination schedule and a heterologous subcutaneous prime and oral booster regimen were assessed in mice and rats, respectively. Mice receiving the oral vaccine compared to control mice showed significantly enhanced post-dose-3 virus-neutralizing antibody, anti-S IgG and IgA production and N-protein-stimulated IFN-γ and IL-2 secretion by T cells. When administered as a booster to rats following parenteral priming with the viral S1 protein, the oral vaccine elicited markedly higher neutralizing antibody titres than did oral placebo booster. A single oral booster following two subcutaneous priming doses elicited serum IgG and mucosal IgA levels similar to those raised by three subcutaneous doses. In conclusion, the oral LTB-adjuvanted multi-epitope SARS-CoV-2 vaccine triggered versatile humoral, cellular and mucosal immune responses, which are likely to provide protection, while also minimizing technical hurdles presently limiting global vaccination, whether by priming or booster programs.HighlightsMigVax-101 is a multi-epitope oral vaccine for SARS-CoV-2.MigVax-101 elicits neutralizing IgG and IgA production and cellular responses in miceMigVax-101 serves as an effective booster in rats to a parenteral anti-S1 vaccine.
Phase-specific pooling of sparse assembly activity by respiration-related brain oscillations
Authors: Folschweiller Shani , Sauer Jonas-Frederic 
Published: June 2021

SummaryNasal breathing affects cognitive functions, but it has remained largely unclear how respiration-driven inputs shape information processing in neuronal circuits. Current theories emphasize the role of neuronal assemblies, coalitions of transiently active pyramidal cells, as the core unit of cortical network computations. Here, we show that respiration-related oscillations (RROs) directly pace the activation of neuronal assemblies in the medial prefrontal cortex (mPFC) of mice. Neuronal assemblies are more efficiently entrained than single neurons and activate preferentially during the descending phase of RROs. At the same time, overlap between individual assemblies is minimized during descending RRO due to the efficient recruitment of GABAergic neurons by assemblies. Our results thus suggest the RROs support cortical operations by defining time windows of enhanced yet segregated assembly activity.
The role of migration in mutant evolution in fragmented populations
Authors: Kreger Jesse , Brown Donovan , Komarova Natalia L. , Wodarz Dominik , Pritchard Justin 
Published: June 2021

AbstractMutant evolution in fragmented populations has been studied extensively in evolutionary biology. With an increased focus on evolutionary dynamics in medical research, quantification of mutant load in fragmented populations with varying levels of migration has become especially important. Examples of fragmented populations are hematopoietic stem cell niches in the bone marrow where cells can re-circulate between niches through the blood, or colonic crypts where movement of cells across different crypts is not thought to be common. Here we use a combination of experiments and theory to investigate the role of migration in mutant distribution. In the case of neutral mutants, the experiments confirmed that while the mean number of mutants is not influenced by migration, the probability distribution is, which manifested itself in a change in the skewedness of the distribution of the mutant numbers in the demes. In the case of disadvantageous mutants, we investigated the phenomenon of the increase in the expected number of mutants compared to that of the selection-mutation balance. In a single deme, this increase is observed when the deme size is lower than the critical size,Nc. In a fragmented system that consists of connected demes with a probability of migration, the increase in mutant numbers above the selection-mutation balance can be maintained in small (N < Nc) demes as long as the migration rate is sufficiently small. The migration rate above which the mutants approach the selection-mutation balance decays exponentially withN/Nc. These findings are relevant in the context of the complex and poorly understood processes that may lead to changes in the clonal composition in tissues and tumors.
Single cell chronoatlas of regenerating mouse livers reveals early Kupffer cell proliferation
Authors: Sánchez-Taltavull Daniel , Brodie Tess , Zindel Joel , Dommann Noëlle , Surewaard Bas G.J. , Keogh Adrian , Mélin Nicolas , Büchi Isabel , Tombolini Riccardo , Kubes Paul , Candinas Daniel , Beldi Guido , Stroka Deborah 
Published: June 2021

SummaryThe liver is exemplar to study tissue regeneration due to its inherent ability of repair and regrowth. It replaces its lost or injured tissue by the proliferation, interaction and temporal coordination of multiple residential cell types. Until now we lacked a detailed description of the specific contributions of each cell type to the regenerative process, and therefore analyzed mouse livers 0, 3, 6, and 24 hours following two-thirds partial hepatectomy (PHx) by single cell RNA-sequencing (scRNA-seq) and mass cytometry. Our resulting genome wide temporal atlas contains the time dependent transcriptional changes in hepatocytes, endothelial cells, bone marrow-derived macrophages (BMDM) and Kupffer cells. In addition, it describes the cell specific contribution of mitogenic growth factors from biliary epithelial, endothelial and stellate cells as well as chemokines and cytokines from BMDM and granulocytes. And interestingly, Kupffer cells as opposed to hepatocytes emerged as the first cell to proliferate presenting a new dynamic in the liver following PHx. Here, we provide a robust data set at cellular resolution to uncover new elements and revisit current dogmas on the mechanisms underlying liver regeneration. To facilitate access to the data, we have launched the portal www.phxatlas.ch in which the scRNA-seq data can be visualized.
Endogenous RNA editing of a nuclear gene BOSS triggers flowering in tomato
Authors: Wang Wenqian , Ye Jie , Yu Chuying , Xie Qingmin , Wang Xin , Yu Huiyang , Song Jianwen , Li Changxing , Cui Long , Han Heyou , Yang Changxian , Li Hanxia , Lu Yongen , Wang Taotao , Zhang Yuyang , Zhang Junhong , Ouyang Bo , Ye Zhibiao 
Published: June 2021

AbstractRNA editing is defined as the production of transcripts with RNA sequences different from those of the DNA template. Most of previous RNA editing studies have focused on organelles, while RNA editing of nuclear transcripts is largely unknown. Here, we describe the first example of nuclear transcript RNA editing in plant, the BOSS RNA editing regulates tomato flowering. The SNP (SNP1) located in the 5’UTR of BOSS gene (the Balancer of SP and SFT) is associated with tomato early flowering, and two transcripts of BOSS produced by SNP1 associated RNA editing show functional differentiation, where BOSS-β transcript promotes flowering while BOSS-α does not. Furthermore, these two transcripts of BOSS are shown to regulate SP (anti-florigen) pathway at transcription level in the shoot apical meristem (SAM). Our findings reveal a new layer of complexity in the control of plant stem cell proliferation and provide the evidence of RNA-editing of a single gene for flowering, suggesting that molecular breeding programs to increase the RNA-editing efficiency may improve the productivity of tomatoes and other agricultural organisms.
Early postnatal activation of the hypoxia pathway disrupts β-cell function
Authors: Yang Juxiang , Hammoud Batoul , Ridler Abigail , Won Kyoung-Jae , Hoshi Toshinori , Stanley Charles A. , Stanescu Diana E. , Ackermann Amanda M. 
Published: June 2021

AbstractHypoxic insults in the perinatal period can lead to persistent hyperinsulinism and profound hypoglycemia in newborns. We studied the impact of the hypoxia-inducible factor 1A (HIF1A) pathway on postnatal β-cell function. Rat pups were treated daily between postnatal day (P)7 to P10 with adaptaquin (AQ), an inhibitor of prolyl hydroxylases, which stabilizes HIF1A. AQ-treated pups were hypoglycemic and had higher plasma insulin concentrations. Their islets had a decreased glucose threshold for insulin secretion, indicative of a delay in β-cell postnatal functional maturation. Histology analyses revealed that AQ-treated pups had increased pancreatic insulin-positive area but no changes in the number of islets or number of β-cells per islet, suggesting larger average β-cell size. AQ-treated rat pups had decreased expression of cell cycle genes and decreased numbers of proliferating β-cells. In conclusion, pharmacologic activation of the HIF1A pathway in the early postnatal period leads to hyperinsulinism, due to the persistence of a low glucose threshold for insulin secretion, and to decreased early postnatal β-cell proliferation, suggesting it can impact adult β-cell mass and diabetes risk.
A deep generative model of 3D single-cell organization
Authors: Donovan-Maiye Rory M. , Brown Jackson M. , Chan Caleb K. , Ding Liya , Yan Calysta , Gaudreault Nathalie , Theriot Julie A. , Maleckar Mary M. , Knijnenburg Theo A. , Johnson Gregory R. 
Published: June 2021

1AbstractWe introduce a framework for end-to-end integrative modeling of 3D single-cell multi-channel fluorescent image data of diverse subcellular structures. We employ stacked conditional β-variational autoencoders to first learn a latent representation of cell morphology, and then learn a latent representation of subcellular structure localization which is conditioned on the learned cell morphology. Our model is flexible and can be trained on images of arbitrary subcellular structures and at varying degrees of sparsity and reconstruction fidelity. We train our full model on 3D cell image data and explore design trade-offs in the 2D setting. Once trained, our model can be used to impute structures in cells where they were not imaged and to quantify the variation in the location of all subcellular structures by generating plausible instantiations of each structure in arbitrary cell geometries. We apply our trained model to a small drug perturbation screen to demonstrate its applicability to new data. We show how the latent representations of drugged cells differ from unperturbed cells as expected by on-target effects of the drugs.2Author summaryIt’s impossible to acquire all the information we want about every cell we’re interested in in a single experiment. Even just limiting ourselves to imaging, we can only image a small set of subcellular structures in each cell. If we are interested in integrating those images into a holistic picture of cellular organization directly from data, there are a number of approaches one might take. Here, we leverage the fact that of the three channels we image in each cell, two stay the same across the data set; these two channels assess the cell’s shape and nuclear morphology. Given these two reference channels, we learn a model of cell and nuclear morphology, and then use this as a reference frame in which to learn a representation of the localization of each subcellular structure as measured by the third channel. We use β-variational autoencoders to learn representations of both the reference channels and representations of each subcellular structure (conditioned on the reference channels of the cell in which it was imaged). Since these models are both probabilistic and generative, we can use them to understand the variation in the data from which they were trained, to generate instantiations of new cell morphologies, and to generate imputations of structures in real cell images to create an integrated model of subcellular organization.