bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental State of Inpatients with COVID-19: a Computational Psychiatry Approach
Authors: Sorokin M.Yu. , Palchikova E.I. , Kibitov A.A. , Kasyanov E.D. , Khobeysh M.A. , Zubova E.Yu. 
Published: August 2021

ABSTRACTThe overload of healthcare systems around the world and the danger of infection have limited the ability of researchers to obtain sufficient and reliable data on psychopathology in hospitalized patients with COVID-19. The relationship between severe SARS-CoV-2 infection and specific mental disturbances remains poorly understood.Aimto reveal the possibility of identifying the typology and frequency of psychiatric syndromes associated with acute COVID-19 using cluster analysis of discrete psychopathological phenomena.Materials and methodsDescriptive data on the mental state of 55 inpatients with COVID-19 were obtained by young-career physicians with psychiatric backgrounds. Classification of observed clinical phenomena was performed with k-means cluster analysis of variables codded from the main psychopathological symptoms. Dispersion analysis with p-level 0.05 was used to reveal the cluster’s differences in demography, parameters of inflammation and respiration function collected on the basis of the original medical records.ResultsThree resulting clusters of patients were identified: persons with anxiety, disorders of fluency and tempo of thinking, mood, attention, motor-volitional sphere, reduced insight, and pessimistic plans for the future (n=11); persons without psychopathology (n=37); persons with disorientation, disorders of memory, attention, fluency, and tempo of thinking, reduced insight (n=7). The development of a certain type of impaired mental state was specifically associated with: age, lung lesions according to computed tomography, saturation, respiratory rate, C-reactive protein level, platelet count.ConclusionThe prevalence and typology of psychiatric disorders in patients with acute COVID-19 were described using the computational psychiatry approach.
Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities
Authors: McLean Huong Q. , Grijalva Carlos G. , Hanson Kayla E. , Zhu Yuwei G. , Deyoe Jessica E. , Meece Jennifer K. , Halasa Natasha B. , Chappell James D. , Mellis Alexandra , Reed Carrie , Belongia Edward A. , Talbot H. Keipp , Rolfes Melissa A. 
Published: August 2021

ABSTRACTOBJECTIVESExamine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection.METHODSPeople with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations.RESULTSThe 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged ≥65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group.CONCLUSIONSBoth children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.
SARS-CoV-2 alpha variant: is it really more deadly? A population level observational study
Authors: Moore Candace Makeda , Sergienko Ruslan , Arbel Ronen 
Published: August 2021

AbstractBackgroundIn 2021 a new variant of SARS-CoV-2, which came to be called the alpha variant, spread around the world. There were conflicting reports on this COVID-19 variant strain’s potentially increased lethality. In Israel, this strain became predominant in a very short time period.MethodsCOVID-19 mortality and case fatality rates were examined in Israel in terms of weekly and cumulative numbers.ResultsCOVID-19 case fatality rates in Israel rose quickly at the beginning of the pandemic and peaked in May 2020. The highest crude mortality came later in the second and third waves, but case the case fatality rates did not rise in 2021 with the increasing dominance of the alpha variant.ConclusionsBased on the results of examining case-fatality and mortality rates, we concluded that while the alpha variant of the virus raised mortality, in line with the fact that it is more infectious than wild-type, once this strain was caught by patients in Israel, it was not more likely to kill them than the original strain
A nuclear role for the Argonaute protein AGO2 in mammalian gametogenesis
Authors: Griffin Kimberly N , Li Haixin , Walters Benjamin William , Wang Huafeng , Kaya Carolyn B , Kanyo Jean , Lam TuKiet , Cox Andy L , Chung Jean-Ju , Lesch Bluma J 
Published: August 2021

SummaryArgonaute 2 (AGO2) is a ubiquitously expressed protein critical for regulation of mRNA translation and vital to animal development. AGO2 protein is found in both cytoplasmic and nuclear compartments, and while its cytoplasmic role is well studied, the biological relevance of nuclear AGO2 is unclear. Here, we address this problem in vivo, using developing spermatogenic cells as a model. Remarkably, we find that AGO2 acts in the germ cell nucleus to positively regulate protein expression. We show that AGO2 dynamically binds both chromatin and nuclear mRNA transcripts of hundreds of genes required for sperm production, and germline conditional knockout (cKO) of Ago2 causes depletion of the corresponding proteins, along with defects in sperm number and morphology. Nuclear AGO2 partners with splicing, export, and chromatin factors to promote transcript export and protein expression. Together, our data reveal an unexpected role for nuclear AGO2 in enhancing expression of developmentally important genes.
A micro-evolutionary change in target binding sites as a key determinant of Ultrabithorax function in Drosophila
Authors: Khan Soumen , Pradhan Saurabh J. , Giraud Guillaume , Bleicher Françoise , Paul Rachel , Merabet Samir , Shashidhara LS 
Published: August 2021

AbstractHox genes encode Homeodomain-containing transcription factors, which specify segmental identities along the anterior-posterior axis. Functional changes in Hox genes have been directly implicated in the evolution of body plans across the metazoan lineage. The Hox protein Ultrabithorax (Ubx) is expressed and required in developing third thoracic (T3) segments in holometabolous insects studied so far, particularly, of the order Coleoptera, Lepidoptera and Diptera. Ubx function is key to specify differential development of the second (T2) and T3 thoracic segments in these insects. While Ubx is expressed in the third thoracic segment in developing larvae of Hymenopteran Apis mellifera, the morphological differences between T2 and T3 are subtle. To identify evolutionary changes that are behind the differential function of Ubx in these two insects, which are diverged for more than 350 million years, we performed comparative analyses of genome wide Ubx-binding sites between Drosophila and Apis. Our studies reveal that a motif with a TAAAT core is a preferred binding site for Ubx in Drosophila, but not in Apis. Biochemical and transgenic assays suggest that in Drosophila, TAAAT core sequence in the Ubx binding sites is required for Ubx-mediated regulation of two of its target genes studied here. CG13222, a gene that is normally upregulated by Ubx and vestigial (vg), whose expression is repressed by Ubx in T3. Interestingly, changing the TAAT site to a TAAAT site was sufficient to bring an otherwise unresponsive enhancer of the vg gene from Apis under the control of Ubx in a Drosophila transgenic assay. Taken together, our results suggest an evolutionary mechanism by which critical wing patterning genes might have come under the regulation of Ubx in the Dipteran lineage.
Superantigens promote Staphylococcus aureus bloodstream infection by eliciting pathogenic interferon-gamma (IFNγ) production that subverts macrophage function
Authors: Tuffs Stephen W. , Goncheva Mariya I. , Xu Stacey X. , Craig Heather C. , Kasper Katherine J. , Choi Joshua , Flannagan Ronald S. , Kerfoot Steven M. , Heinrichs David E. , McCormick John K. 
Published: August 2021

ABSTRACTStaphylococcus aureus is a foremost bacterial pathogen responsible for a vast array of human diseases. Staphylococcal superantigens (SAgs) constitute a family of potent exotoxins secreted by S. aureus, and SAg genes are found ubiquitously in human isolates. SAgs bind directly to MHC class II molecules and T cell receptors, driving extensive T cell activation and cytokine release. Although these toxins have been implicated in serious disease including toxic shock syndrome, we aimed to further elucidate the mechanisms by which SAgs contribute to staphylococcal pathogenesis during septic bloodstream infections. As most conventional mouse strains respond poorly to staphylococcal SAgs, we utilized transgenic mice encoding humanized MHC class II molecules (HLA-DR4) as these animals are much more susceptible to SAg activity. Herein, we demonstrate that SAgs contribute to the severity of S. aureus bacteremia by increasing bacterial burden, most notably in the liver. We established that S. aureus bloodstream infection severity is mediated by CD4+ T cells and interferon-gamma (IFNγ) is produced to very high levels during infection in a SAg-dependent manner. Bacterial burden and disease severity were reduced by antibody blocking of IFNγ, phenocopying isogenic SAg deletion mutant strains. Additionally, cytokine analysis demonstrated that the immune system was skewed towards a proinflammatory response that was reduced by IFNγ blocking. Infection kinetics and flow cytometry analyses suggested this was a macrophage driven mechanism, which was confirmed through macrophage depletion experiments. Further validation with human leukocytes indicated that excessive IFNγ allowed S. aureus to replicate at a higher rate within macrophages. Together, this suggests that SAgs promote S. aureus survival by manipulating immune responses that would otherwise be effective at clearing S. aureus. This work implicates SAg toxins as critical targets for preventing persistent or severe S. aureus disease.
Embryonic and aglomerular kidney development in the bay pipefish, Syngnathus leptorhynchus
Authors: Maters Bianca R. , Stevenson Emily , Vize Peter D. 
Published: August 2021

AbstractIn this report we describe the embryogenesis of the bay pipefish, Syngnathus leptorhynchus, and the organogenesis of its aglomerular kidney. Early development was analyzed via a series of montages and images documenting embryos collected from the brood pouches of pregnant males. Despite differences in terminal morphology between pipefish and common teleost models such as medaka and zebrafish, the embryogenesis of these highly advanced fishes is generally similar to that of other fishes. One of the unique features of these fishes is their utilization of an aglomerular kidney. Histological analysis revealed a single long, unbranched kidney tubule in late embryos. The development and structure of this organ was further investigated by cloning the sodium potassium ATPase alpha subunit, atp1a, from S. leptorhynchus and developing whole mount fluorescent in situ hybridization protocols for embryos of this species. Fluorescent stereoscopic and confocal visualization techniques were then used to characterize the 3D morphology of aglomerular kidneys in intact embryos. In all embryonic stages characterized, the aglomerular kidney is a single unbranched tube extending from just behind the head to the cloaca.
Chlorophyll fluorescence-based estimates of photosynthetic electron transport in Arctic phytoplankton assemblages
Authors: Sezginer Yayla , Suggett David J. , Izett Robert W. , Tortell Philippe D. 
Published: August 2021

AbstractWe employed Fast Repetition Rate fluorometry for high-resolution mapping of marine phytoplankton photophysiology and primary productivity in the Lancaster Sound and Barrow Strait regions of the Canadian Arctic Archipelago in the summer of 2019. Continuous ship-board analysis of chlorophyllavariable fluorescence demonstrated relatively low photochemical efficiency over most of the cruise-track, with the exception of localized regions within Barrow Strait where there was increased vertical mixing and proximity to land-based nutrient sources. Along the full transect, we observed strong non-photochemical quenching of chlorophyll fluorescence, with relaxation times longer than the 5-minute period used for dark acclimation. Such long-term quenching effects complicate continuous underway acquisition of fluorescence amplitude-based estimates of photosynthetic electron transport rates, which rely on dark acclimation of samples. As an alternative, we employed a new algorithm to derive electron transport rates based on analysis of fluorescence relaxation kinetics, which does not require dark acclimation. Direct comparison of kinetics- and amplitude-based electron transport rate measurements demonstrated kinetic-based estimates were, on average, 2-fold higher than amplitude-based values. The magnitude of decoupling between the two electron transport rate estimates increased in association with photophysiological diagnostics of nutrient stress. Discrepancies between electron transport rate estimates likely resulted from the use of different photophysiological parameters to derive the kinetics- and amplitude-based algorithms, and choice of numerical model used to fit variable fluorescence curves and analyze fluorescence kinetics under actinic light. Our results highlight environmental and methodological influences on fluorescence-based productivity estimates, and prompt discussion of best-practices for future underway fluorescence-based efforts to monitor phytoplankton photosynthesis.
Calibration free counting of low molecular copy numbers in single DNA-PAINT localization clusters
Authors: Stein J. , Stehr F. , Jungmann R. , Schwille P. 
Published: August 2021

ABSTRACTSingle-Molecule Localization Microscopy (SMLM) has revolutionized light microscopy by enabling optical resolutions down to a few nanometer. Yet, localization precisions commonly not suffice to visually resolve single subunits in molecular assemblies or multimeric complexes. Since each targeted molecule contributes localizations during image acquisition, molecular counting approaches to reveal the target copy numbers within localization clusters have been continuously proposed since the early days of SMLM, most of which rely on preliminary knowledge of the dye photo-physics or on a calibration to a reference. Previously, we developed localization-based Fluorescence Correlation Spectroscopy (lbFCS) as an absolute ensemble counting approach for the SMLM-variant DNA-Points Accumulation for Imaging in Nanoscale Topography (PAINT), for the first time circumventing the necessity for reference calibrations. Here, we present a revised framework termed lbFCS+ which allows absolute counting of copy numbers for individual localization clusters in a single DNA-PAINT image. In lbFCS+, absolute counting in individual clusters is achieved via precise measurement of the local hybridization rates of the fluorescently-labeled oligonucleotides (‘imagers’) employed in DNA-PAINT imaging. In proof-of-principle experiments on DNA origami nanostructures, we demonstrate the ability of lbFCS+ to truthfully determine molecular copy numbers and imager association and dissociation rates in well-separated localization clusters containing up to six docking strands. We show that lbFCS+ allows to resolve heterogeneous binding dynamics enabling the distinction of stochastically generated and a priori indistinguishable DNA assemblies. Beyond advancing quantitative DNA-PAINT imaging, we believe that lbFCS+ could find promising applications ranging from bio-sensing to DNA computing.
Arf6 anchors Cdr2 nodes at the cell cortex to control cell size at division
Authors: Opalko Hannah E. , Miller Kristi E. , Kim Hyun-Soo , Vargas-Garcia Cesar , Singh Abhyudai , Keogh Michael-Christopher , Moseley James B. 
Published: August 2021

ABSTRACTFission yeast cells prevent mitotic entry until a threshold cell surface area is reached. The protein kinase Cdr2 contributes to this size control system by forming multiprotein nodes that inhibit Wee1 at the medial cell cortex. Cdr2 node anchoring at the cell cortex is not fully understood. Through a genomic screen, we identified the conserved GTPase Arf6 as a component of Cdr2 signaling. Cells lacking Arf6 failed to divide at a threshold surface area and instead shifted to volume-based divisions at increased overall size. Arf6 stably localized to Cdr2 nodes in its GTP-bound but not GDP-bound state, and its GEF (guanine nucleotide exchange factor) Syt22 was required for both Arf6 node localization and proper size at division. In arf6Δ mutants, Cdr2 nodes detached from the membrane and exhibited increased dynamics. These defects were enhanced when arf6Δ was combined with other node mutants. Our work identifies a regulated anchor for Cdr2 nodes that is required for cells to sense surface area.
Single cell based high-throughput Ig and TCR repertoire sequencing analysis in rhesus macaques
Authors: Walsh Evan S. , Tollison Tammy S. , Brochu Hayden N. , Shaw Brian I. , Diveley Kayleigh R. , Chou Hsuan , Law Lynn , Kirk Allan D. , Gale Michael , Peng Xinxia 
Published: August 2021

AbstractRecent advancements in microfluidics and high-throughput sequencing technologies have enabled recovery of paired heavy- and light-chains of immunoglobulins (Ig) and VDJ- and VJ-chains of T cell receptors (TCR) from thousands of single cells simultaneously in humans and mice. Despite rhesus macaques being one of the most well-studied model organisms for the human adaptive immune response, high-throughput single cell immune repertoire sequencing assays are not yet available due to the complexity of these polyclonal receptors. Here we employed custom primers that capture all known rhesus macaque Ig and TCR isotypes and chains that are fully compatible with a commercial solution for single cell immune repertoire profiling. Using these rhesus specific assays, we sequenced Ig and TCR repertoires in over 60,000 cells from cryopreserved rhesus PBMC, splenocytes, and FACS-sorted B and T cells. We were able to recover every Ig isotype and TCR chain, measure clonal expansion in proliferating T cells, and pair Ig and TCR repertoires with gene expression profiles of the same single cells. Our results establish the ability to perform high-throughput immune repertoire analysis in rhesus macaques at the single cell level.
Interdomain linkers regulate histidine kinase activity by controlling subunit interactions
Authors: Maschmann Zachary , Chandrasekaran Siddarth , Chua Teck Khiang , Crane Brian R. 
Published: August 2021

AbstractBacterial chemoreceptors regulate the cytosolic multi-domain histidine kinase CheA through largely unknown mechanisms. Residue substitutions in the peptide linkers that connect the P4 kinase domain to the P3 dimerization and P5 regulatory domain affect CheA basal activity and activation. To understand the role that these linkers play in CheA activity, the P3-to-P4 linker (L3) and P4-to-P5 linker (L4) were extended and altered in variants ofThermotoga maritima (Tm)CheA. Flexible extensions of the L3 and L4 linkers in CheA-LVI (linker variant 1) allowed for a well-folded kinase domain that retained wild-type (WT)­like binding affinities for nucleotide and normal interactions with the receptor-coupling protein CheW. However, CheA-LV1 autophosphorylation activity registered -50-fold lower compared to WT. Neither a WT nor LV1 dimer containing a single P4 domain could autophosphorylate the P1 substrate domain. Autophosphorylation activity was rescued in variants with extended L3 and L4 linkers that favor helical structure and heptad spacing. Autophosphorylation depended on linker spacing and flexibility and not on sequence. Pulse-dipolar electron-spin resonance (ESR) measurements with spin-labeled ATP analogs indicated that CheA autophosphorylation activity inversely correlated with the proximity of the P4 domains within the dimers of the variants. Despite their separation in primary sequence and space, the L3 and L4 linkers also influence the mobility of the P1 substrate domains. In all, interactions of the P4 domains, as modulated by the L3 and L4 linkers, affect domain dynamics and autophosphorylation of CheA, thereby providing potential mechanisms for receptors to regulate the kinase.
Investigating the Lipid Selectivity of Membrane Proteins in Heterogeneous Nanodiscs
Authors: Keener James E. , Jayasekera Hiruni S. , Marty Michael T. 
Published: August 2021

ABSTRACTThe structure and function of membrane proteins can be significantly impacted by the surrounding lipid environment, but membrane protein-lipid interactions in lipid bilayers are often difficult to study due to their transient and polydisperse nature. Here, we used two native mass spectrometry (MS) approaches to investigate how the Escherichia coli ammonium transporter (AmtB) and aquaporin Z (AqpZ) selectively remodel their local lipid environment in heterogeneous lipoprotein nanodiscs. First, we used gas-phase ejection to isolate the membrane protein with bound lipids from heterogeneous nanodiscs with different combinations of lipids. Second, we used solution-phase detergent extraction as an orthogonal approach to study membrane protein remodeling of lipids in the nanodisc with native MS. Our results showed that Triton X-100 and LDAO retain lipid selectivity that agrees with gas-phase ejection, but C8E4 distorts some preferential lipid interactions. Both approaches reveal that AmtB has a few selective binding sites for phosphatidylcholine (PC) lipids, is selective for binding phosphatidylglycerols (PG) overall, and is nonselective for phosphatidylethanolamines (PE). In contrast, AqpZ prefers either PC or PG over PE and prefers PC over PG. Overall, these experiments provide a detailed picture of how membrane proteins bind different lipid head groups in the context of mixed lipid bilayers.