bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Chordwise Functionally Graded Flexural Rigidity in Flapping Wings Using a Two-Dimensional Pitch-Plunge Model
Authors: Reade Joseph , Jankauski Mark 
Published: August 2021

AbstractInsect wings are heterogeneous structures, with flexural rigidity varying one to two orders of magnitude over the wing surface. This heterogeneity influences the deformation the flapping wing experiences during flight. However, it is not well understood how this flexural rigidity gradient affects wing performance. Here, we develop a simplified 2D model of a flapping wing as a pitching, plunging airfoil using the assumed mode method and unsteady vortex lattice method to model the structural and fluid dynamics, respectively. We conduct parameter studies to explore how variable flexural rigidity affects mean lift production, power consumption and the forces required to flap the wing. We find that there is an optimal flexural rigidity distribution that maximizes lift production; this distribution generally corresponds to a 3:1 ratio between the wing’s flapping and natural frequencies, though the ratio is sensitive to flapping kinematics. For hovering flight, the optimized flexible wing produces 20% more lift and requires 15% less power compared to a rigid wing but needs 20% higher forces to flap. Even when flapping kinematics deviate from those observed during hover, the flexible wing outperforms the rigid wing in terms of aerodynamic force generation and power across a wide range of flexural rigidity gradients. Peak force requirements and power consumption are inversely proportional with respect to flexural rigidity gradient, which may present a trade-off between insect muscle size and energy storage requirements. The model developed in this work can be used to efficiently investigate other spatially variant morphological or material wing features moving forward.
Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding
Authors: Furniss R. Christopher D. , Kadeřábková Nikol , Barker Declan , Bernal Patricia , Maslova Evgenia , Antwi Amanda A.A. , McNeil Helen E. , Pugh Hannah L. , Dortet Laurent , Blair Jessica M.A. , Larrouy-Maumus Gerald , McCarthy Ronan R. , Gonzalez Diego , Mavridou Despoina A.I. 
Published: August 2021

ABSTRACTAntimicrobial resistance in Gram-negative bacteria is one of the greatest threats to global health. New antibacterial strategies are urgently needed, and the development of antibiotic adjuvants that either neutralize resistance proteins or compromise the integrity of the cell envelope is of ever-growing interest. Most available adjuvants are only effective against specific resistance proteins. Here we demonstrate that disruption of cell envelope protein homeostasis simultaneously compromises several classes of resistance determinants. In particular, we find that impairing DsbA-mediated disulfide bond formation incapacitates diverse β-lactamases and destabilizes mobile colistin resistance enzymes. Furthermore, we show that chemical inhibition of DsbA sensitizes multidrug-resistant clinical isolates to existing antibiotics and that the absence of DsbA, in combination with antibiotic treatment, substantially increases the survival of Galleria mellonella larvae infected with multidrug- resistant Pseudomonas aeruginosa. This work lays the foundation for the development of novel antibiotic adjuvants that function as broad-acting resistance breakers.IMPACT STATEMENTDisruption of disulfide bond formation sensitizes resistant Gram- negative bacteria expressing β-lactamases and mobile colistin resistance enzymes to currently available antibiotics.
SNR-efficient distortion-free diffusion relaxometry imaging using ACcelerated Echo-train shifted EPTI (ACE-EPTI)
Authors: Dong Zijing , Wang Fuyixue , Wald Lawrence , Setsompop Kawin 
Published: August 2021

AbstractPurposeTo develop an efficient acquisition technique for distortion-free diffusion MRI and diffusion-relaxometry.MethodsA new ACcelerated Echo-train shifted Echo-Planar Time-resolved Imaging (ACE-EPTI) technique is developed to achieve high-SNR, distortion- and blurring-free diffusion and diffusion-relaxometry imaging. ACE-EPTI employs a newly designed variable density spatiotemporal encoding with self-navigation capability, that allows submillimeter in-plane resolution using only 3-shot. Moreover, an echo-train-shifted acquisition is developed to achieve minimal TE, together with an SNR-optimal readout length, leading to ~30% improvement in SNR efficiency over single-shot EPI. To recover the highly accelerated data with high image quality, a tailored subspace image reconstruction framework is developed, that corrects for odd/even-echo phase difference, shot-to-shot phase variation, and the B0 field changes due to field drift and eddy currents across different dynamics. After the phase-corrected subspace reconstruction, artifacts-free high-SNR diffusion images at multiple TEs are obtained with varying T2* weighting.ResultsSimulation, phantom and in-vivo experiments were performed, which validated the 3-shot spatiotemporal encoding provides accurate reconstruction at submillimeter resolution. The use of echo-train shifting and optimized readout length improves the SNR-efficiency by 27-36% over single-shot EPI. The reconstructed multi-TE diffusion images were demonstrated to be free from distortion (susceptibility and eddy currents) and phase/field variation induced artifacts. These improvements of ACE-EPTI enable improved diffusion tensor imaging and rich multi-TE information for diffusion-relaxometry analysis.ConclusionACE-EPTI was demonstrated to be an efficient and powerful technique for high-resolution diffusion imaging and diffusion-relaxometry, which provides high SNR, distortion- and blurring-free, and time-resolved multi-echo images by a fast 3-shot acquisition.
Zika virus induces mitotic catastrophe in human neural progenitors by triggering unscheduled mitotic entry in the presence of DNA damage while functionally depleting nuclear PNKP
Authors: Rychlowska Malgorzata , Agyapong Abigail , Weinfeld Michael , Schang Luis M. 
Published: August 2021

AbstractVertical transmission of Zika virus (ZIKV) leads with high frequency to congenital ZIKV syndrome (CZS), whose worst outcome is microcephaly. However, the mechanisms of congenital ZIKV neurodevelopmental pathologies, including direct cytotoxicity to neural progenitor cells (NPC), placental insufficiency, and immune responses, remain incompletely understood. At the cellular level, microcephaly typically results from death or insufficient proliferation of NPC or cortical neurons. NPCs replicate fast, requiring efficient DNA damage responses to ensure genome stability. Like congenital ZIKV infection, mutations in the polynucleotide 5’-kinase 3’-phosphatase (PNKP) gene, which encodes a critical DNA damage repair enzyme, results in recessive syndromes often characterized by congenital microcephaly with seizures (MCSZ). We thus tested whether there were any links between ZIKV and PNKP.Here we show that two PNKP phosphatase inhibitors or PNKP knockout inhibited ZIKV replication. PNKP relocalized from the nucleus to the cytoplasm in infected cells, co-localizing with the marker of ZIKV replication factories (RF) NS1 and resulting in functional nuclear PNKP depletion. Although infected NPC accumulated DNA damage, they failed to activate the DNA damage checkpoint kinases Chk1 and Chk2. ZIKV also induced activation of cytoplasmic CycA/CDK1 complexes, which trigger unscheduled mitotic entry. Inhibition of CDK1 activity inhibited ZIKV replication and the formation of RF, supporting a role of cytoplasmic CycA/CDK1 in RF morphogenesis. In brief, ZIKV infection induces mitotic catastrophe resulting from unscheduled mitotic entry in the presence of DNA damage. PNKP and CycA/CDK1 are thus host factors participating in ZIKV replication in NPC, and pathogenesis to neural progenitor cells.SignificanceThe 2015-2017 Zika virus (ZIKV) outbreak in Brazil and subsequent international epidemic revealed the strong association between ZIKV infection and congenital malformations, mostly neurodevelopmental defects up to microcephaly. The scale and global expansion of the epidemic, the new ZIKV outbreaks (Kerala state, India, 2021), and the potential burden of future ones pose a serious ongoing risk. However, the cellular and molecular mechanisms resulting in microcephaly remain incompletely understood. Here we show that ZIKV infection of neuronal progenitor cells results in cytoplasmic sequestration of an essential DNA repair protein itself associated with microcephaly, with the consequent accumulation of DNA damage, together with an unscheduled activation of cytoplasmic CDK1/Cyclin A complexes in the presence of DNA damage. These alterations result in mitotic catastrophe of neuronal progenitors, which would lead to a depletion of cortical neurons during development.
COVID-19 infection among health care workers: Experience in Base Hospital Wathupitiwala, Sri Lanka
Authors: Samaranayake W.A.M.P. , Jayawardena G.P.C. , Roshan A.L.L. , Wijewardene M.A.M. , Siraj M.I. 
Published: August 2021

AbstractCoronavirus disease 2019 (COVID-19) is a serious global health pandemic resulting in high mortality and morbidity. Frontline health care workers (HCWs) are at an increased risk of the acquisition of severe acute respiratory syndrome coronavirus-2 infection (SARS CoV-2) due to their close interaction with infected patients (1, 2). Also, HCWs can serve as reservoirs of SARS CoV-2 cross-transmission both in community and hospital settings (1). However, the extent of COVID-19 infection among HCWs in Sri Lanka is understudied.ObjectivesThis study determined the incidence, demographic characteristics, and risk exposure behavior of HCWs who tested positive for SARS CoV-2 at Base Hospital Wathupitiwala. Furthermore, the rate of acquisition of SARS CoV-2 following COVISHIELD/ChAdOx1 nCoV-19 and Sinopharm /BBIBP-CorV vaccines in HCWs were studied.MethodsA retrospective cross-sectional descriptive analysis was conducted from May 2021 to August 2021 for a total of 818 HCWs.ResultsHundred and twenty-four HCWs (15.16%) were tested positive for COVID-19. The mean age of infected HCWs was 46.27 years and the majority were females (74.19%). Among all infected persons, 54 (43.55%) were nurses/midwives, 39 (31.45%) were clinical supportive staff and 12(9.68%) were medical officers. The number of infected HCWs rapidly escalated and a total of 64(51.61%) HCWs got an infection during August/2021. No source was identified in most of them (34.68%) followed by community acquisition (33.87%). Thirty-five HCWs (28.23%) had acquired infection during a hospital setting or had a high-risk exposure in recent history. Among hospital-related infections, 37.91% of HCWs had shared meals or shared sleeping rooms with an infected workmate. The majority of the HCWs were tested by the infection control unit as symptomatic screening (70.16%) followed by contact tracing (20.16%). Fifty-six (45.16%) HCWs had a history of single or multiple comorbidities. The vast majority of HCWs (95.97%) presented as mild to asymptomatic disease that followed an uneventful recovery. Body aches, headache, fever, and sore throat were the most commonly reported symptoms among them. Among the five HCWs required therapeutic oxygen supplementation, two unvaccinated HCWs succumbed to the infection. The rate of breakthrough infection among HCWs was 8.93%. The acquisition of disease was significantly higher among unvaccinated HCWs than partially (p<0.0001) or fully vaccinated (p<0.0001) HCWs with either type of vaccine.ConclusionsProtecting HCWs remains a challenge in resource-poor settings. The risk of infection fueled by very contagious circulating variants is continuously high even though vaccination has shown clear benefits in preventing mortality and severe infection. Therefore, all healthcare workers should be vaccinated while ensuring continuous infection control measures in the hospital setting.
A toolkit for quantification of biological age from blood-chemistry and organ-function-test data: BioAge
Authors: Kwon Dayoon , Belsky Daniel W. 
Published: August 2021

AbstractMethods to quantify biological aging are emerging as new measurement tools for epidemiology and population science and have been proposed as surrogate measures for healthy lifespan extension in geroscience clinical trials. Publicly available software packages to compute biological aging measurements from DNA methylation data have accelerated dissemination of these measures and generated rapid gains in knowledge about how different measures perform in a range of datasets. Biological age measures derived from blood chemistry data were introduced at the same time as the DNA methylation measures and, in multiple studies, demonstrate superior performance to these measures in prediction of healthy lifespan. However, their dissemination has been slow by comparison, resulting in a significant gap in knowledge. We developed a software package to help address this knowledge gap. The BioAge R package, available for download at GitHub (http://github.com/dayoonkwon/BioAge), implements three published methods to quantify biological aging based on analysis of chronological age and mortality risk: Klemera-Doubal Biological Age, PhenoAge, and homeostatic dysregulation. The package allows users to parametrize measurement algorithms using custom sets of biomarkers, to compare the resulting measurements to published versions of the Klemera-Doubal method and PhenoAge algorithms, and to score the measurements in new datasets. We applied BioAge to safety lab data from the CALERIE™ randomized controlled trial, the first-ever human trial of long-term calorie restriction in healthy, non-obese adults, to test effects of intervention on biological aging. Results contribute evidence that CALERIE intervention slowed biological aging. BioAge is a toolkit to facilitate measurement of biological age for geroscience.
Identification and Interaction Analysis of Molecular Markers in Myocardial Infarction by Integrated Bioinformatics Analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: August 2021

AbstractMyocardial infarction (MI) is the leading cardiovascular diseases in worldwide, yet relatively little is known about the genes and signaling pathways involved in MI progression. The present investigation aimed to elucidate potential crucial candidate genes and pathways in MI. expression profiling by high throughput sequencing dataset (GSE132143) was downloaded from the Gene Expression Omnibus (GEO) database, which included data from 20 MI samples and 12 normal control samples. Differentially expressed genes (DEGs) were identified using t-tests in the DESeq2 R package. These DEGs were subsequently investigated by Gene Ontology (GO) and pathway enrichment analysis, a protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed and analyzed. Hub genes were validated by receiver operating characteristic curve (ROC) analysis. In total, 958 DEGs were identified, of which 480 were up regulated and 478 were down regulated. GO and pathway enrichment analysis results revealed that the DEGs were mainly enriched in, immune system, neuronal system, response to stimulus, and multicellular organismal process. A PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network was constructed by using Cytoscape software, and CFTR, CDK1, RPS13, RPS15A, RPS27, NOTCH1, MRPL12, NOS2, CCDC85B and ATN1 were identified as the hub genes. Our results highlight the important roles of the genes including CFTR, CDK1, RPS13, RPS15A, RPS27, NOTCH1, MRPL12, NOS2, CCDC85B and ATN1 in MI pathogenesis or therapeutic management.
SampleQC: robust multivariate, multi-celltype, multi-sample quality control for single cell data
Authors: Macnair Will , Robinson Mark D. 
Published: August 2021

AbstractQuality control (QC) is a critical component of single-cell RNA-seq (scRNA-seq) processing pipelines. Current approaches to QC implicitly assume that datasets are comprised of one celltype, potentially resulting in biased exclusion of rare celltypes. We introduce SampleQC, which robustly fits a Gaussian mixture model across multiple samples, and improves sensitivity and reduces bias compared to current approaches. We show via simulations that SampleQC is less susceptible to exclusion of rarer celltypes. We also demonstrate SampleQC on a complex real dataset (867k cells over 172 samples). SampleQC is general, is implemented in R, and could be applied to other data types.
Cap analysis of gene expression (CAGE) sequencing reveals alternative promoter usage in complex disease
Authors: Dahale Sonal , Ruiz-Orera Jorge , Silhavy Jan , Hubner Norbert , van Heesch Sebastiaan , Pravenec Michal , Atanur Santosh S 
Published: August 2021

AbstractThe role of alternative promoter usage in tissue specific gene expression has been well established, however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) tag sequencing from the left ventricle (LV) of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, the Brown Norway (BN) to understand role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites (TSS) in the rat LV, including 1,970 novel cardiac TSS resulting in new transcripts. We identified 27 genes with alternative promoter usage between SHR and BN which could lead to protein isoforms differing at the amino terminus between two strains. Additionally, we identified 475 promoter switching events where a shift in TSS usage was within 100bp between SHR and BN, altering length of the 5’ UTR. Genomic variants located in the shifting promoter regions showed significant allelic imbalance in F1 crosses, confirming promoter shift. We found that the insulin receptor gene (Insr) showed a switch in promoter usage between SHR and BN in heart and liver. The Insr promoter shift was significantly associated with insulin levels and blood pressure within a panel of BXH/HXB recombinant inbred (RI) rat strains. This suggests that the hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.
Cardiomyocyte GSK-3β deficiency induces cardiac progenitor cell proliferation in the ischemic heart through paracrine mechanisms
Authors: Yusuf Ayesha M. , Qaisar Rizwan , Al-Tamimi Abaher O. , Jayakumar Manju Nidagodu , Woodgett James R. , Koch Walter J. , Ahmad Firdos 
Published: August 2021

AbstractCardiomyopathy is an irreparable loss and novel strategies are needed to induce resident cardiac progenitor cell (CPC) proliferation in situ to enhance the possibility of cardiac regeneration. Here we sought to identify the potential roles of glycogen synthase kinase-3β (GSK-3β), a critical regulator of cell proliferation and differentiation, in CPC proliferation post-myocardial infarction (MI).Cardiomyocyte-specific conditional GSK-3β knockout (cKO) and littermate control mice were employed and challenged with MI. Though cardiac left ventricular chamber dimension (LVID) and contractile functions were comparable at two-week post-MI, cKO mice displayed significantly preserved LV chamber and contractile function vs. control mice at four-weeks post-MI. Consistent with protective phenotypes, an increased percentage of c-kit-positive cells (KPCs) were observed in the cKO hearts at four and six-weeks post-MI which was accompanied by increased levels of cardiomyocyte proliferation. Further analysis revealed that the observed increased number of KPCs in the ischemic cKO hearts was mainly from a cardiac lineage as the majority of identified KPCs were negative for the hematopoietic lineage marker, CD45. Mechanistically, cardiomyocyte-GSK-3β profoundly suppresses the expression and secretion of growth factors, including basic-FGF angiopoietin-2, erythropoietin, stem cell factor (SCF), PDGF-BB, G-CSF, and VEGF, post-hypoxia.In conclusion, our findings strongly suggest that loss of cardiomyocyte-GSK-3β promotes cardiomyocyte and resident CPC proliferation post-MI. The induction of cardiomyocyte and CPC proliferation in the ischemic cKO hearts is potentially regulated by autocrine and paracrine signaling governed by dysregulated growth factors post-MI. A strategy to inhibit cardiomyocyte GSK-3β could be helpful for the promotion of in situ cardiac regeneration post-ischemic injury.
The rise of grasslands is linked to atmospheric CO2decline in the late Palaeogene
Authors: Palazzesi Luis , Hidalgo Oriane , Barreda Viviana D. , Forest Félix , Höhna Sebastian 
Published: August 2021

ABSTRACTGrasslands are predicted to experience a major biodiversity change by the year 2100 in part due to recent and projected increases in atmospheric CO2concentration. A better understanding of how grasslands have responded to past environmental changes will help predict the outcome of current and future environmental changes. Here, we explore the relationship between past atmospheric CO2and temperature fluctuations and the shifts in diversification rate of grasses (Poaceae) and daisies (Asteraceae), two exceptionally species-rich grassland families (∼11,000 and ∼23,000 species, respectively). To this end, we developed a novel Bayesian approach that simultaneously estimates diversification-rates through time from time-calibrated phylogenies and correlations between environmental variables and diversification rates. Additionally, we developed a new statistical approach that incorporates the information of the distribution of missing species in the phylogeny. We found strong evidence supporting a simultaneous increase in diversification rates for daisies and grasses after the most significant reduction of atmospheric CO2in the Cenozoic (∼34 Mya). The fluctuations of paleo-temperatures, however, appear not to have had a significant relationship with the diversification of these grassland families. Overall, our results shed new light on our understanding of the origin of grasslands in the context of past environmental changes.