bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disparities in Vulnerability to Severe Complications from COVID-19 in the United States
Authors: Wiemers Emily E. , Abrahams Scott , AlFakhri Marwa , Hotz V. Joseph , Schoeni Robert F. , Seltzer Judith A. 
Published: May 2020

AbstractThis paper provides the first nationally representative estimates of vulnerability to severe complications from COVID-19 overall and across race-ethnicity and socioeconomic status. We use the Panel Study of Income Dynamics (PSID) to examine the prevalence of specific health conditions associated with complications from COVID-19 and to calculate, for each individual, an index of the risk of severe complications from respiratory infections developed by DeCaprio et al. (2020). We show large disparities across race-ethnicity and socioeconomic status in the prevalence of conditions which are associated with the risk of severe complications from COVID-19. Moreover, we show that these disparities emerge early in life, prior to age 65, leading to higher vulnerability to such complications. While vulnerability is highest among older adults regardless of their race-ethnicity or socioeconomic status, our results suggest particular attention should also be given to the risk of adverse outcomes in midlife for non-Hispanic Blacks, adults with a high school degree or less, and low-income Americans.
An Ontology-based Approach to Guide and Document Variable and Data Source Selection and Data Integration Process to Support Integrative Data Analysis in Cancer Outcomes Research
Authors: Zhang Hansi , Guo Yi , Bian Jiang 
Published: May 2020

AbstractBackgroundTo reduce cancer mortality and improve cancer outcomes, it is critical to understand the various cancer risk factors (RFs) across different domains (e.g., genetic, environmental, and behavioral risk factors) and levels (e.g., individual, interpersonal, and community levels). However, prior research on RFs of cancer outcomes, has primarily focused on individual level RFs due to the lack of integrated datasets that contain multi-level, multi-domain RFs. Further, the lack of a consensus and proper guidance on systematically identify RFs also increase the difficulty of RF selection from heterogenous data sources in a multi-level integrative data analysis (mIDA) study. More importantly, as mIDA studies require integrating heterogenous data sources, the data integration processes in the limited number of existing mIDA studies are inconsistently performed and poorly documented, and thus threatening transparency and reproducibility.MethodsInformed by the National Institute on Minority Health and Health Disparities (NIMHD) research framework, we (1) reviewed existing reporting guidelines from the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network and (2) developed a theory-driven reporting guideline to guide the RF variable selection, data source selection, and data integration process. Then, we developed an ontology to standardize the documentation of the RF selection and data integration process in mIDA studies.ResultsWe summarized the review results and created a reporting guideline—ATTEST—for reporting the variable selection and data source selection and integration process. We provided an ATTEST check list to help researchers to annotate and clearly document each step of their mIDA studies to ensure the transparency and reproducibility. We used the ATTEST to report two mIDA case studies and further transformed annotation results into sematic triples, so that the relationships among variables, data sources and integration processes are explicitly standardized and modeled using the classes and properties from OD-ATTEST.ConclusionOur ontology-based reporting guideline solves some key challenges in current mIDA studies for cancer outcomes research, through providing (1) a theory-driven guidance for multi-level and multi-domain RF variable and data source selection; and (2) a standardized documentation of the data selection and integration processes powered by an ontology, thus a way to enable sharing of mIDA study reports among researchers.
Three-dimensional understanding of the morphological complexity of the human uterine endometrium
Authors: Yamaguchi Manako , Yoshihara Kosuke , Suda Kazuaki , Nakaoka Hirofumi , Yachida Nozomi , Ueda Haruka , Sugino Kentaro , Mori Yutaro , Yamawaki Kaoru , Tamura Ryo , Ishiguro Tatsuya , Motoyama Teiichi , Watanabe Yu , Okuda Shujiro , Tainaka Kazuki , Enomoto Takayuki 
Published: May 2020

SummaryThe histological basis of the human uterine endometrium has been established by 2D observation. However, the fundamental morphology of endometrial glands is not sufficiently understood because these glands have complicated winding and branching patterns. To construct a big picture of endometrial gland structure, we performed tissue-clearing-based 3D imaging of human uterine endometrial tissue. Our 3D immunohistochemistry and 3D layer analyses revealed that endometrial glands formed a plexus network in the stratum basalis, similar to the rhizome of grass. We then extended our method to assess the 3D morphology of adenomyosis, a representative “endometrium-related disease”, and observed 3D morphological features including direct invasion of endometrial glands into the myometrium and an ant colony-like network of ectopic endometrial glands within the myometrium. Thus, 3D analysis of the human endometrium and endometrium-related diseases will be a promising approach to better understand the pathologic physiology of the human endometrium.
Significant functional differences despite morphological and molecular similarity in fully differentiated matched Conditionally Reprogrammed (CRC) and Feeder free dual SMAD inhibited expanded human nasal epithelial cells
Authors: Awatade Nikhil T. , Wong Sharon L. , Pandzic Elvis , Slapetova Iveta , Capraro Alexander , Zhong Ling , Turgutoglu Nihan , Fawcett Laura K. , Whan Renee M. , Jaffe Adam , Waters Shafagh A. 
Published: May 2020

AbstractBackgroundPatient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Advances in culture techniques have improved expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. However, considerable variation in response to CFTR modulators is observed even when using similar ALI culture techniques. We aimed to address if variation in response reflects true biological differences between patients or technical differences as a consequence of different culture expansion methods.MethodsNasal epithelial brushings from 14 individuals (CF=9; non-CF=5) were collected, then equally divided and expanded under conditional reprogramming culture (CRC) and feeder-serum-free “dual-SMAD inhibition” (SMADi) methods. Expanded cells from each culture were differentiated with proprietary PneumaCult™-ALI media. Morphology (Immunofluorescence), global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility, and ion transport) were compared in CRCALIand SMADiALIunder basal and CFTR corrector treated (VX-809) conditions.ResultsNo significant difference in the structural morphology or global proteomics profile were observed. Barrier integrity and cilia motility were significantly different, despite no difference in cell junction morphology or cilia abundance. Epithelial Sodium Channels and Calcium-activated Chloride Channel activity did not differ but CFTR mediated chloride currents were significantly reduced in SMADiALIcompare to their CRCALIcounterparts.ConclusionAlteration of cellular physiological functionin vitrooccurs were more prominent than structural and differentiation potential in airway ALI. Since culture conditions significantly influence CFTR activity, this could lead to false conclusions if data from different labs are compared against each other without specific reference ranges.
Core binding factor leukemia hijacks T-cell prone PU.1 antisense promoter
Authors: van der Kouwe E. , Heller G. , Czibere A. , Castilla L.H. , Delwel R. , Di Ruscio A. , Ebralidze A.K. , Forte M. , Kazianka L. , Kornauth C. , Le T. , Lind K. , Monteiro Barbosa I.A. , Pichler A. , Pulikkan J.A. , Schmolke A-S , Sill H. , Sperr W.R. , Spittler A. , Trinh B. Q. , Valent P. , Vanura K. , Welner R.S. , Zuber J. , Tenen D.G. , Staber P.B. 
Published: May 2020

Summary paragraphThe blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of the hematopoietic master regulator PU.11–4. PU.1 gene expression is regulated through enhancer-promoter interactions within a topologically associated domain (TAD)5,6. PU.1 levels increase during myeloid differentiation while failure to do so results in myeloid leukemia7. In contrast, T-cell differentiation requires PU.1 to be completely switched off8–10. Little is known about the precise mechanisms of PU.1 repression, physiological as in T-cell differentiation, or pathological as in leukemia. Here we demonstrate that the down-regulation of PU.1 mRNA is a dynamic process involving an alternative promoter11in intron 3 that is induced by RUNX transcription factors driving noncoding antisense transcription. Core binding factor (CBF) fusions, RUNX1-ETO and CBFβ-MYH11 in t(8;21) and inv(16) acute myeloid leukemia (AML)12, activate the PU.1 antisense promoter, thus shifting from sense towards antisense transcription and blocking myeloid differentiation. In patients with CBF-AML, we found that an elevated antisense/sense ratio represents a hallmark compared to normal karyotype AML or healthy CD34+ cells. Competitive interaction of the enhancer with the proximal or the antisense promoter are at the heart of differential PU.1 expression during myeloid and T-cell development. Leukemic CBF fusions thus utilize a physiologic mechanism employed by T-cells to decrease sense PU.1 transcription. Our results identify the first example of a sense/antisense promoter competition as a crucial functional switch for gene expression perturbation by oncogenes. This novel basic disease mechanism reveals a previously unknown Achilles heel for future precise therapeutic targeting of oncogene-induced chromatin remodeling.
The mutational landscape of human olfactory G protein-coupled receptors
Authors: Jimenez Ramón Cierco , Casajuana-Martin Nil , García-Recio Adrián , Alcántara Lidia , Pardo Leonardo , Campillo Mercedes , Gonzalez Angel 
Published: May 2020

ABSTRACTOlfactory receptors (ORs) constitute a large family of sensory proteins that enable us to recognize a wide range of chemical volatiles in the environment. By contrast to the extensive information about human olfactory thresholds for thousands of odorants, studies of the genetic influence on olfaction are limited to a few examples. Here, we analyzed a compendium of 118,057 natural variants in human ORs collected from the public domain. OR mutations were categorized depending on their genomic and protein contexts, as well as their frequency of occurrence in several human populations. Functional interpretation of the natural changes was estimated from the increasing knowledge of the structure and function of the G protein-coupled receptor (GPCR) family, to which ORs belong. Our analysis reveals an extraordinary diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a significant number of changes occurring at structural conserved regions. A particular attention is paid to mutations in positions linked to the conserved GPCR activation mechanism that could imply phenotypic variation in the olfactory perception. An interactive web application (available athttp://lmc.uab.cat/hORMdb) was developed for the management and visualization of this mutational dataset.
From wing shape to fluid dynamics in the barn owl (Tyto alba)
Authors: Cheney Jorn A , Stevenson Jonathan PJ , Durston Nick E , Song Jialei , Maeda Masateru , Windsor Shane P , Usherwood James R , Bomphrey Richard J 
Published: May 2020

AbstractBirds morph their wings and tail in order to glide under a wide range of aerodynamic conditions. Gross wing morphing has been described in a multitude of studies, but the finer details of wing morphing are still unknown. Here, we measured the changes in wing shape and pose in a barn owl,Tyto alba, when gliding across a range of fifteen self-selected speeds. We found thatT. albadoes not use fine-wing shape control to glide at slow speeds in steady conditions, with the measured wing shapes being highly consistent across all flights. Instead,T. albarelied upon wing postural control (gross pitch) and changes in both tail shape and pose to modulate aerodynamic force. A consistent wing shape provides an exceptional aerodynamic tool for understanding gliding flight in birds through postural change and tail morphing. This geometry was used as the basis for computational fluid dynamics simulations which gave very similar wake measurements and weight support to those measured in flight. This geometry is provided here to assist other researchers interested in exploring the fluid dynamics behind gliding flight in birds.
Loss of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis
Authors: Alkan H Furkan , Vesely Paul W , Hackl Hubert , Foßelteder Johannes , Vander Heiden Matthew G , Pichler Martin , Hoefler Gerald , Bogner-Strauss Juliane G 
Published: May 2020

AbstractBackgroundAspartate biosynthesis and its delivery to the cytosol can be crucial for tumor growthin vivo.However, the impact of aspartate synthesis on metastasis has not been studied. We previously described that loss-of-aspartate glutamate carrier 1 (SLC25A12 or AGC1), an important component of the malate-aspartate shuttle, impairs cytosolic aspartate levels, NAD+/NADH ratio, mitochondrial respiration, and tumor growth. Here, we report the impact of AGC1-knockdown on metastasis.ResultsAGC1 expression is positively correlated with worse patient prognosis in many cancers. AGC1-knockdown in mouse lung carcinoma and melanoma cell lines leads to increased pulmonary metastasis following subcutaneous or intravenous injections, respectively. On the other hand, conventionalin vitrometastasis assays show no indication of increased metastasis capacity of AGC1-knockdown cells.ConclusionThis study highlights that certain branches of metabolism impact tumor growth and tumor metastasis differently. In addition, it also argues that commonly known metastasis indicators, including EMT genes, cell migration, or colony formation do not always reflect the metastatic capacityin vivo.
Recombination of 2Fe-2S ferredoxins reveals differences in the inheritance of thermostability and midpoint potential
Authors: Campbell Ian J. , Kahanda Dimithree , Atkinson Joshua T. , Sparks Othneil N. , Kim Jinyoung , Tseng Chia-Ping , Verduzco Rafael , Bennett George N. , Silberg Jonathan J. 
Published: May 2020

ABSTRACTHomologous recombination can be used to create enzymes that exhibit distinct activities and stabilities from proteins in nature, allowing researchers to overcome component limitations in synthetic biology. To investigate how recombination affects the physical properties of an oxidoreductase that transfers electrons, we created ferredoxin (Fd) chimeras by recombining distantly-related cyanobacterial and cyanomyophage Fds that present similar midpoint potentials but distinct thermostabilities. Fd chimeras having a wide range of amino acid substitutions retained the ability to coordinate an iron-sulfur cluster, although their thermostabilities varied with the fraction of residues inherited from each parent. The midpoint potentials of chimeric Fds also varied. However, all of the synthetic Fds exhibited midpoint potentials outside of the parental protein range. Each of the chimeric Fds could also be used to build synthetic pathways that support electron transfer between Fd-NADP reductase and sulfite reductase inEscherichia coli, although the chimeric Fds varied in the expression required to support similar levels of cellular electron transfer. These results show how recombination can be used to rapidly diversify the physical properties of protein electron carriers and reveal differences in the inheritance of thermostability and electrochemical properties. Furthermore, they illustrate how electron transfer efficiencies of chimeric Fds can be rapidly evaluated using a synthetic electron transfer pathway.
Macrophage Inflammatory State Influences Susceptibility to Lysosomal Damage
Authors: Wong Amanda O. , Marthi Matangi , Owusu Irene A. , Wobus Christiane E. , Swanson Joel A. 
Published: May 2020

AbstractMacrophages possess mechanisms for reinforcing the integrity of their endolysosomal membranes against damage. This property, termed inducible renitence, was previously reported for macrophages stimulated with LPS, peptidoglycan, IFN-γ, or TNF-α. Here, we expanded the macrophage subtypes examined to include populations with well-defined functional rolesin vivo: classically activated macrophages (CA-Mφ), alternatively activated macrophages (AA-Mφ), and regulatory macrophages (Reg-Mφ). We determined that renitence is a property of CA-Mφ and Reg-Mφ, but not of AA-Mφ. Furthermore, LPS-activated macrophages possess features of both CA-Mφ and Reg-Mφ, based on their cytokine secretion profiles. As the generation of these three classes of renitent macrophages required exposure to LPS, a Toll-like receptor (TLR) ligand, we assessed whether TLR stimulation generally induced renitence. Stimulation of TLRs 2/1, 3, and 4 induced renitence, whereas stimulation of TLRs 7/8 and 9 induced modest levels of lysosomal damage protection. Renitence induced by TLR stimulation required the signaling adaptors MyD88 and TRIF. Surprisingly, the specific signaling adaptor usage requirements for some TLRs differed from those established for canonical TLR signaling. Of note, renitence induced by LPS, a TLR4 ligand, required signaling through TRIF but not MyD88. Consistent with this pattern, the type I IFN response, which is triggered by LPS stimulation through a TRIF-dependent, MyD88-independent pathway, contributed to renitence. A biologically relevant type I IFN trigger in macrophages, murine norovirus-1 (MNV-1) infection, also induced renitence. This work establishes the concept that susceptibility to lysosomal damage within macrophages varies according to inflammatory state and depends on the type I IFN response.Summary sentenceMacrophages of distinct polarization states exhibit varying degrees of susceptibility to lysosomal damage reflecting their functional roles in host defense and immune regulation
Physical activity is positively related to local functional connectivity in adolescents’ brains
Authors: Ruotsalainen Ilona , Glerean Enrico , Karvanen Juha , Gorbach Tetiana , Renvall Ville , Syväoja Heidi J. , Tammelin Tuija H. , Parviainen Tiina 
Published: May 2020

AbstractAdolescents have experienced decreased aerobic fitness levels and insufficient physical activity levels over the past decades. While both physical activity and aerobic fitness are related to physical and mental health, little is known concerning how they manifest in the brain during this stage of development, characterized by significant physical and psychosocial changes. Previous investigations have demonstrated associations of physical activity and aerobic fitness with the brain’s functional connectivity in both children and adults. However, it is difficult to generalize these results to adolescents because the development of functional connectivity has unique features during adolescence. Here, we examined how physical activity and aerobic fitness are associated with local and interhemispheric functional connectivity of the adolescent brain, as measured with resting-state functional magnetic resonance imaging (fMRI). Physical activity was measured by hip-worn accelerometers, and aerobic fitness by a maximal 20-m shuttle run test. We found that higher levels of moderate-to-vigorous physical activity, but not aerobic fitness, were linked to increased local functional connectivity as measured by regional homogeneity in 13–16-year-old participants. However, we did not find evidence for significant associations between adolescents’ physical activity or aerobic fitness and interhemispheric connectivity, as indicated by homotopic connectivity. These results suggest that physical activity, but not aerobic fitness, is related to local functional connectivity in adolescents. Moreover, physical activity shows an association with a specific brain area involved in motor functions but did not display any widespread associations with other brain regions. These results can advance our understanding of the behavior-brain associations in adolescents.
Genus-wide characterization of bumblebee genomes reveals variation associated with key ecological and behavioral traits of pollinators
Authors: Sun Cheng , Huang Jiaxing , Wang Yun , Zhao Xiaomeng , Su Long , Thomas Gregg W.C. , Zhao Mengya , Zhang Xingtan , Jungreis Irwin , Kellis Manolis , Vicario Saverio , Sharakhov Igor V. , Bondarenko Semen M. , Hasselmann Martin , Kim Chang N , Paten Benedict , Penso-Dolfin Luca , Wang Li , Chang Yuxiao , Gao Qiang , Ma Ling , Ma Lina , Zhang Zhang , Zhang Hongbo , Zhang Huahao , Ruzzante Livio , Robertson Hugh M. , Zhu Yihui , Liu Yanjie , Yang Huipeng , Ding Lele , Wang Quangui , Xu Weilin , Liang Cheng , Itgen Michael W. , Mee Lauren , Sadd Ben M. , Cao Gang , Zhang Ze , Hahn Matthew , Schaack Sarah , Barribeau Seth M. , Williams Paul H. , Waterhouse Robert M. , Mueller Rachel Lockridge 
Published: May 2020

AbstractBumblebees are a diverse group of globally important pollinators in natural ecosystems and for agricultural food production. With both eusocial and solitary lifecycle phases, and some social parasite species, they are especially interesting models to understand social evolution, behavior, and ecology. Reports of many species in decline point to pathogen transmission, habitat loss, pesticide usage, and global climate change, as interconnected causes. These threats to bumblebee diversity make our reliance on a handful of well-studied species for agricultural pollination particularly precarious. To broadly sample bumblebee genomic and phenotypic diversity, wede novosequenced and assembled the genomes of 17 species, representing all 15 subgenera, producing the first genus-wide quantification of genetic and genomic variation potentially underlying key ecological and behavioral traits. The species phylogeny resolves subgenera relationships while incomplete lineage sorting likely drives high levels of gene tree discordance. Five chromosome-level assemblies show a stable 18-chromosome karyotype, with major rearrangements creating 25 chromosomes in social parasites. Differential transposable element activity drives changes in genome sizes, with putative domestications of repetitive sequences influencing gene coding and regulatory potential. Dynamically evolving gene families and signatures of positive selection point to genus-wide variation in processes linked to foraging, diet and metabolism, immunity and detoxification, as well as adaptations for life at high altitudes. These high-quality genomic resources capture natural genetic and phenotypic variation across bumblebees, offering new opportunities to advance our understanding of their remarkable ecological success and to identify and manage current and future threats.