bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport
Authors: Zhang Letian , Piipponen Minna , Liu Zhuang , Li Dongqing , Bian Xiaowei , Toma Maria A. , Sommar Pehr , Xu Landén Ning 
Published: July 2022

ABSTRACTAfter a skin injury, keratinocytes switch from a state of homeostasis to one of regeneration leading to the reconstruction of the epidermal barrier. The regulatory mechanism of gene expression underpinning this key switch during human skin wound healing is enigmatic. Long noncoding RNAs (lncRNAs) constitute a new horizon in the understanding of the regulatory programmes encoded in the mammalian genome. By comparing the transcriptome of an acute human wound and skin from the same donor as well as keratinocytes isolated from these paired tissue samples, we generated a list of lncRNAs showing changed expression in keratinocytes during wound repair. Our study focused on HOXC13-AS, a recently evolved human lncRNA specifically expressed in epidermal keratinocytes, and we found that its expression was temporally downregulated during wound healing. In line with its enrichment in suprabasal keratinocytes, HOXC13-AS was found to be increasingly expressed during keratinocyte differentiation, but its expression was reduced by EGFR signalling. After HOXC13-AS knockdown or overexpression in human primary keratinocytes undergoing differentiation induced by cell suspension or calcium treatment and in organotypic epidermis, we found that keratinocyte differentiation was promoted, while the cell inflammatory response was suppressed. Moreover, RNA pull-down assays followed by mass spectrometry and RNA immunoprecipitation analysis revealed that mechanistically HOXC13-AS sequestered the coat complex subunit alpha (COPA) protein and interfered with Golgi-to-endoplasmic reticulum (ER) molecular transport, resulting in ER stress and enhanced keratinocyte differentiation. In summary, we identified HOXC13-AS as a crucial regulator of human epidermal differentiation.
Mucosal administration of anti-bacterial antibody provides long-term cross-protection against Pseudomonas aeruginosa respiratory infection
Authors: Pitiot Aubin , Ferreira Marion , Parent Christelle , Boisseau Chloé , Cortes Mélanie , Bouvart Laura , Paget Christophe , Heuzé-Vourc’h Nathalie , Sécher Thomas 
Published: July 2022

AbstractBacterial respiratory infections, associated with acute, sometimes recurrent infections and with chronic respiratory diseases, are a major threat for human health. Mucosal administration of therapeutic antibodies (Ab), using the airways as a delivery route, has a tremendous opportunity to benefit to patients with respiratory infections, with remarkable preclinical achievements in both viral and bacterial respiratory infection models and ongoing clinical developments. The primary mode of action of anti-infective Ab delivered through the airways is pathogen neutralization and to a lesser extent, Fc-mediated direct recruitment of immune effectors to facilitate their elimination. Using a mouse model of acute pneumonia induced by P. aeruginosa, a bacterium frequently associated with multidrug resistance and a high rate of recurrence, we characterized an immunomodulatory mode of action of anti-bacterial Ab. Beyond the rapid and efficient containment of the primary infection, the anti-infective Ab delivered through the airways harnessed adaptive immunity to provide a long-term response, preventing from a secondary pathogen infection. This effect is specific and dependent on the Ab dose, intensity of infection and antigen expression by the pathogen upon primary infection. As shown by adoptive transfer experiments, it is mediated by a sustained and protective humoral immune response. Interestingly, the long-lasting response protected partially against secondary infections due to heterologous P. aeruginosa strains. Overall, our findings suggest that mucosal delivery of Ab through the airways offers a dual advantage: a rapid onset of action to neutralize respiratory bacteria and a long-term protection against secondary infections, thereby opening novel perspectives for the development of anti-infective antibody delivered to the lung mucosa, to treat respiratory infections.
Deep Proteome Profiling Reveals Signatures of Age and Sex Differences in Paw Skin and Sciatic Nerve of Naïve Mice
Authors: Xian Feng , Sondermann Julia Regina , Varela David Gomez , Schmidt Manuela 
Published: July 2022

AbstractThe age and sex of studied animals profoundly impact experimental outcomes in animal-based preclinical biomedical research. However, most preclinical studies in mice use a wide-spanning age range from 4 to 14 weeks and do not assess study parameters in male and female mice in parallel. This raises concerns regarding reproducibility and neglects potentially relevant age and sex differences. Furthermore, the molecular setup of tissues in dependence of age and sex is unknown in naïve mice. Here, we employed an optimized quantitative proteomics workflow in order to deeply profile mouse paw skin and sciatic nerve (SCN) – two tissues, which are crucially implicated in nociception and pain as well as diverse diseases induced by inflammation, trauma, and demyelination. Remarkably, we uncovered significant differences when comparing (i) male and female mice, and, in parallel, (ii) adolescent mice (4 weeks) with adult mice (14 weeks). Age was identified as a major discriminator of analyzed samples irrespective of tissue type. Moreover, our analysis enabled us to decipher protein subsets and networks that exhibit differential abundance in dependence on the age and/or sex of mice. Notably, among these were proteins and signaling pathways with known relevance for (patho)physiology, such as homeostasis and epidermal signaling in skin and, in SCN, multiple myelin proteins and regulators of neuronal development. In addition, extensive comparisons with available databases revealed that we quantified approx. 50% of gene products that were implicated in distinct skin diseases and pain, many of which exhibited significant abundance changes in dependence on age and/or sex. Taken together, our study emphasizes the need for accurate age matching and uncovers hitherto unknown sex and age differences at the level of proteins and protein networks. Overall, we provide a unique systems biology proteome resource, which facilitates mechanistic insights into somatosensory and skin biology in dependence on age and sex - a prerequisite for successful preclinical studies in mouse disease models.Graphic workflowThe Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.
Single-Cell Multi-Modal GAN (scMMGAN) reveals spatial patterns in single-cell data from triple negative breast cancer
Authors: Amodio Matthew , Youlten Scott E , Venkat Aarthi , San Juan Beatriz P , Chaffer Christine , Krishnaswamy Smita 
Published: July 2022

AbstractExciting advances in technologies to measure biological systems are currently at the forefront of research. The ability to gather data along an increasing number of omic dimensions has created a need for tools to analyze all of this information together, rather than siloing each technology into separate analysis pipelines. To advance this goal, we introduce a framework called the Single-Cell Multi-Modal GAN (scMMGAN) that integrates data from multiple modalities into a unified representation in the ambient data space for downstream analysis using a combination of adversarial learning and data geometry techniques. The framework’s key improvement is an additional diffusion geometry loss with a new kernel that constrains the otherwise over-parameterized GAN network. We demonstrate scMMGAN’s ability to produce more meaningful alignments than alternative methods on a wide variety of data modalities, and that its output can be used to draw conclusions from real-world biological experimental data. We highlight data from an experiment studying the development of triple negative breast cancer, where we show how scMMGAN can be used to identify novel gene associations and we demonstrate that cell clusters identified only on the scRNAseq data occur in localized spatial patterns that reveal insights on the spatial transcriptomic images.
Duet: SNP-Assisted Structural Variant Calling and Phasing Using Oxford Nanopore Sequencing
Authors: Zhou Yekai , Leung Amy Wing-Sze , Ahmed Syed Shakeel , Lam Tak-Wah , Luo Ruibang 
Published: July 2022

AbstractBackgroundWhole genome sequencing (WGS) using the long-read Oxford Nanopore Technologies (ONT) MinION sequencer provides a cost-effective option for structural variant (SV) detection in clinical applications. Despite the advantage of using long reads, however, accurate SV calling and phasing are still challenging.ResultsWe introduce Duet, an SV detection tool optimized for SV calling and phasing using ONT data. The tool uses novel features integrated from both SV signatures and single-nucleotide polymorphism (SNP) signatures, which can accurately distinguish SV haplotype from a false signal. Duet was benchmarked against state-of-the-art tools on multiple ONT sequencing datasets of sequencing coverage ranging from 8X to 40X. At low sequencing coverage of 8X, Duet performs better than all other tools in SV calling, SV genotyping and SV phasing. When the sequencing coverage is higher (20X to 40X), the F1-score for SV phasing is further improved in comparison to the performance of other tools, while its performance of SV genotyping and SV calling remains comparable or higher than other tools.ConclusionDuet can perform accurate SV calling, SV genotyping and SV phasing using low-coverage ONT data, making it very useful for low-coverage genomes. It has great performance when scaled to high-coverage genomes, which is adaptable to various clinical applications. Duet is open source and is available at https://github.com/yekaizhou/duet.
Sleep alterations in a mouse model of Spinocerebellar ataxia type 3
Authors: Tsimpanouli Maria-Efstratia , Ghimire Anjesh , Barget Anna J. , Weston Ridge , Paulson Henry L. , Costa Maria do Carmo , Watson Brendon O. 
Published: July 2022

ABSTRACTBackgroundSpinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodegenerative disorders, their impact on SCA3 is unknown.ObjectivesUsing state-of-the art spectrographic measurements, we sought to quantitatively characterize sleep electroencephalography (EEG) in a SCA3 transgenic mouse model with confirmed disease phenotype.MethodsWe first measured motor phenotypes in 18–31-week-old homozygous and hemizygous SCA3 YACMJD84.2 mice and non-transgenic wild-type littermate mice during lights-on and lights-off periods. We next implanted electrodes to obtain 12-hour (zeitgeber time 0-12) EEG recordings for three consecutive days when the mice were 26–36 weeks old. We then analyzed EEG-based sleep structure data to quantify differences between homozygous, hemizygous, and wild-type mice.ResultsCompared to wild-type littermates, SCA3 homozygous mice display: i) increased duration of rapid-eye movement sleep (REM) and fragmentation in all sleep and wake states; ii) higher beta power oscillations during REM and non-REM (NREM); and iii) additional spectral power band alterations during REM and wake.ConclusionsOur data show that sleep architecture and EEG spectral power are dysregulated in homozygous SCA3 mice, indicating that common sleep-related etiologic factors may underlie mouse and human SCA3 phenotypes.
Direct Cell Extraction of Membrane Proteins for Structure-Function Analysis
Authors: Drulyte Ieva , Gutgsell Aspen Rene , Lloris-Garcerá Pilar , Liss Michael , Geschwindner Stefan , Radjainia Mazdak , Frauenfeld Jens , Löving Robin 
Published: July 2022

AbstractMembrane proteins are the largest group of therapeutic targets in a variety of disease areas and yet, they remain particularly difficult to investigate. We have developed a novel one-step approach for the incorporation of membrane proteins directly from cells into lipid Salipro nanoparticles. Here, with the pannexin1 channel as a case study, we demonstrate the applicability of this method for structurefunction analysis using SPR and cryo-EM.
The FANCC-FANCE-FANCF complex is evolutionarily conserved and regulates meiotic recombination
Authors: Singh Dipesh Kumar , Gamboa Rigel Salinas , Singh Avinash Kumar , Walkemeir Birgit , Van Leene Jelle , De Jaeger Geert , Siddiqi Imran , Guerois Raphael , Crismani Wayne , Mercier Raphael 
Published: July 2022

AbstractAt meiosis, programmed meiotic DNA double-strand breaks are repaired via homologous recombination, resulting in crossovers (COs). From a large excess of DNA double-strand breaks that are formed, only a small proportion gets converted into COs because of active mechanisms that restrict CO formation. The Fanconi anemia (FA) complex proteins AtFANCM, MHF1, and MHF2 were previously identified in a genetic screen as anti-CO factors that function during meiosis in Arabidopsis thaliana. Here, pursuing the same screen, we identify FANCC as a new anti-CO gene. FANCC was previously only identified in mammals because of low primary sequence conservation. We show that FANCC, and its physical interaction with FANCE-FANCF, is conserved from vertebrates to plants. Further, we show that FANCC, together with its subcomplex partners FANCE and FANCF, regulates meiotic recombination. Mutations of any of these three genes partially rescues CO-defective mutants, which is particularly marked in female meiosis. Functional loss of FANCC, FANCE, or FANCF results in synthetic meiotic catastrophe with the pro-CO factor MUS81. This work reveals that FANCC is conserved outside mammals and has an anti-CO role during meiosis together with FANCE and FANCF.
The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart
Authors: Taliani Valeria , Buonaiuto Giulia , Desideri Fabio , Setti Adriano , Santini Tiziana , Galfrè Silvia , Schirone Leonardo , Mariani Davide , Frati Giacomo , Valenti Valentina , Sciarretta Sebastiano , Perlas Emerald , Nicoletti Carmine , Musarò Antonio , Ballarino Monica 
Published: July 2022

ABSTRACTLong noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes-of-action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodelling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing and whole-mountin situhybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the myocardium and ventricular hypo-trabeculation. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications.
Biochemical noise enables a single optogenetic input to control identical cells to track asymmetric and asynchronous reference signals
Authors: May Michael P , Munsky Brian 
Published: July 2022

AbstractOptogenetics is a powerful technology to control synthetic gene circuits using external and computer-programmable light inputs. Like all biological processes, these systems are subject to intrinsic noise that arises from the stochastic process of gene regulation at the single-cell level. Many engineers have sought to mitigate this noise by developing more complex embedded bio-circuits, but recent work has shown that noise-exploiting stochastic controllers could enable new control strategies that take advantage of noise, rather than working against it. These noise-exploiting controllers were initially proposed to solve a single-input-multi-output stationary control problem, where symmetry was broken in a means reminiscent to the concept of Maxwell’s Demon. In this paper, we extend those results and show through computation that transient, asymmetric, and asynchronous stochastic control of the single-input-multi-output (SIMO) control problem is posible to achieve by cycling through different controllers in time. We show that such a method is able control two cells to two different periodic fates with different frequencies and different phases despite the use of only one control input.
Increased landscape disturbance and streamflow variability threaten fish biodiversity in the Red River catchment, USA
Authors: Mollenhauer Robert , Mouser Joshua B. , Roland Victor L. , Brewer Shannon K. 
Published: July 2022

AbstractAimStream fish distributions are hypothesized to be strongly associated with landscape characteristics at multiple scales. Variation in flow regimes and intensity of landscape disturbance are associated with stream fish distributions; however, relationships are poorly understood in many high‐diversity regions. Our objective was to identify occurrence relationships between fish distributions and streamflow and landscape characteristics in the south‐central United States.LocationOur study area was the central Red River catchment in Oklahoma, Texas and Arkansas, USA.MethodsWe used existing fish surveys to model the occurrence of a diverse, warmwater assemblage among hydraulic response units (HRUs). We used multispecies occupancy modelling to identify variation in occurrence probability among 111 stream fishes in relation to landscape disturbance and flow regime characteristics.ResultsWe found occurrence relationships with landscape disturbance and 11 metrics comprising all flow‐regime components. The relationships varied within both major species groups and some genera. Frequency and duration were the most common metrics underlying flow regime relationships. More common stream fishes tended to be positively associated with higher levels of landscape disturbance and flow regime metrics representing variability; conversely, narrow‐ranged fishes tended to be negatively associated. Occurrence relationships with flow metrics representing high‐flow events were predominately negative. As expected, many species were strongly associated with ecoregion with landscape disturbance and flow relationships held constant.Main conclusionsOur study informs land use and water management decisions and stream fish conservation at multiple spatial scales. Collectively, the findings suggest potential homogenization of the Red River fish assemblage with increased landscape disturbance and streamflow variability. A reduction in landscape disturbance and maintenance of natural flow patterns at coarser scales may benefit endemic and narrow‐ranged fishes. Our findings also help guide finer‐scale land use and water management decisions by identifying stream network areas with a high occurrence probability of less tolerant fishes.
Nomogram for predicting in‐hospital mortality of nonagenarians with community‐acquired pneumonia
Authors: Zan Yumin , Song Weiwei , Wang Yu , Shao Jiaofang , Wang Zhiyong , Zhao Weihong , Wu Jianqing , Xu Wei 
Published: July 2022

AimNonagenarians with community‐acquired pneumonia (CAP) have a high mortality rate; however, appropriate tools for reliable severity assessment in this population are lacking. The current study aimed to evaluate the risk factors and establish a nomogram to predict in‐hospital mortality of nonagenarians with CAP.MethodsIn total, 304 patients aged ≥90 years who were admitted with CAP to Jiangsu Provincial People's Hospital and Jiangsu Provincial Hospital of Chinese Medicine between 2014 and 2020 were retrospectively analyzed. Clinical information, laboratory imaging results and pathogen detection were retrieved. Significant variables independently associated with CAP were identified by a logistic regression model, and a nomogram prediction model was constructed. The nomogram was compared with the widely used assessments: CURB‐65, PSI and National Early Warning Score (NEWS) scores.ResultsUnivariate and multivariate logistic regression analyses identified gender, blood urea nitrogen, C‐reactive protein‐to‐albumin ratio, Charlson Comorbidity Index and systemic immune inflammation index as independent factors that affect the prognosis. We created a nomogram for CAP based on these risk factors. The nomogram had a bootstrapped concordance index of 0.796 and was well‐calibrated in the decision analysis curve range of 0.1–0.98. The area under the curve was 0.796 (95% CI: 0.74–0.85), significantly higher than for CURB‐65, PSI and NEWS scores (P < 0.05).ConclusionsOur nomogram model can predict the outcome of hospitalized nonagenarians with CAP and guide clinicians to provide better treatment, leading to improved prognosis and reduced mortality. Geriatr Gerontol Int 2022; 22: 635–641.
Spillover effects in Chinese carbon, energy and financial markets
Authors: Cao Guangxi , Xie Fei , Ling Meijun 
Published: July 2022

AbstractAs China's carbon market continues to develop, its close connection with the financial and energy markets is becoming increasingly apparent. A systematic study of the spillover effects between markets is important, as it can help prevent excessive fluctuations in carbon prices. With this in mind, this study proposes a time‐varying parameter vector autoregression with Lanne–Nyberg decomposition extended joint connectedness approach to analyze quantitatively the spillover effects in the “carbon–energy–financial” system. Empirical results show that a bidirectional spillover effect exists among markets. Not only does the carbon market have the most pronounced return (volatility) linkages with the natural gas (clean energy) market, but the information connected with the energy markets is also more closely linked than with the financial markets. We also find that market fluctuations, caused by the China–US trade conflict and the COVID‐19 pandemic, have increased spillovers in the system.
Analyst following, financial constraint, and audit opinion shopping: From the perspective of earning management
Authors: Lin Zhijun , Wang Longmei 
Published: July 2022

AbstractThis study examines the relationships among analyst following, financial constraint, and audit opinion shopping from the perspective of earnings management, taking a sample of Chinese A‐share firms from 2008 to 2018. We find that analyst following alleviates firm's accrued earnings management activities which restrain opinion shopping behaviors; on the other hand, it prompts real earnings management activities that encourage firm's effort to audit opinion shopping. Earnings management has a mediation effect on the positive association between analyst following and audit opinion shopping. Corporate financial constraint amplifies the positive effect of analyst following on opinion shopping.