bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sirtuin gene isoforms and genomic sequences of mouse and humans: Divergence across species
Authors: Zhang Xiaomin , Azhar Gohar , Ameer Fathima S. , Crane Jasmine , Wei Jeanne Y. 
Published: April 2022

AbstractBackgroundThere are seven sirtuin genes in the mammalian genome. Each sirtuin gene contains multiple exons, and is likely to undergo alternative splicing, thereby increasing sirtuin gene diversity. Since the alternatively spliced isoforms tend to increase with advancing age, it is important to study the effect of sequence change on isoform function. Additionally, the divergence of isoform patterns between human and mouse will help us to properly interpret the findings from animal models, especially in age-related studies. Recently, more than 20 human sirtuin isoforms have been identified, but whether the mouse genome might have similar isoforms remains incompletely established.MethodsThe mRNA, protein and genomic DNA sequences of mouse sirtuin genes, as well as the transcription factor binding sites, including that of SRF, were analyzed. A cellular stress model with serum deprivation and restoration was used to reflect the blood supply and nutrients level changes in the ischemia and reperfusion condition, and the expression of sirtuin isoform was assessed.ResultsHere, we report the identification of 15 mouse sirtuin isoforms, of which over half have not been previously reported. Exon skipping was the main event, which led to domain losses in the nuclear localization signal, nucleolar localization signal, and/or the mitochondrial targeting sequence among sirtuin isoforms. Among 7 sirtuin genes, 6 mouse sirtuin genes had different exon numbers versus that of human sirtuin genes. Only the sirtuin-2 gene had the same number of exons in both human and mouse. However, there were differences in the sirtuin-2 gene isoforms and the regulatory domains between the two species. The expression of sirtuin gene isoforms under serum stress was also different.ConclusionsAlternative splicing increases both sirtuin transcriptome and proteome diversity. However, the sirtuin isoforms were not well conserved between human and mouse, which should be taken into consideration when extrapolating animal studies for human physiology and pathology. Our results will help to elucidate the role of sirtuin genes in the regulation of cellular stress response, including ischemia and reperfusion. We propose that the existence of the CArG and CArG-like sequences in sirtuin genes may imply a role for SRF in the sirtuin family transcriptional regulation.
A coupled atrioventricular-aortic setup for in-vitro hemodynamic study of the systemic circulation: Design, Fabrication, and Physiological relevancy
Authors: Alavi Rashid , Aghilinejad Arian , Wei Heng , Niroumandi Soha , Wieman Seth , Pahlevan Niema M 
Published: April 2022

AbstractIn-vitro models of the systemic circulation have gained a lot of interest for fundamental understanding of cardiovascular dynamics and for applied hemodynamic research. In this study, we introduce a physiologically accurate in-vitro hydraulic setup that models the hemodynamics of the coupled atrioventricular-aortic system. This unique experimental simulator has three major components: 1) an arterial system consisting of a human-scale artificial aorta along with the main branches, 2) an artificial left ventricle (LV) sac connected to a programmable piston-in-cylinder pump for simulating cardiac contraction and relaxation, and 3) an artificial left atrium (LA). The setup is designed in such a way that the basal LV is directly connected to the aortic root via an aortic valve, and to the LA via an artificial mitral valve. As a result, two-way hemodynamic couplings can be achieved for studying the effects that the LV, aorta, and LA have on each other. The collected pressure and flow measurements from this setup demonstrate a remarkable correspondence to clinical hemodynamics. We also investigate the physiological relevancies of isolated effects on cardiovascular hemodynamics of various major global parameters found in the circulatory system, including LV contractility, LV preload, heart rate, aortic compliance, and peripheral resistance. Subsequent control over such parameters ultimately captures physiological hemodynamic effects of LV systolic dysfunction, preload (cardiac) diseases, and afterload (arterial) diseases. The detailed design and fabrication of the proposed setup is also provided.
Genome-wide detection of human variants that disrupt intronic branchpoints
Authors: Zhang Peng , Philippot Quentin , Ren Weicheng , Lei Wei-Te , Li Juan , Stenson Peter D. , Palacín Pere Soler , Colobran Roger , Boisson Bertrand , Zhang Shen-Ying , Puel Anne , Pan-Hammarström Qiang , Zhang Qian , Cooper David N. , Abel Laurent , Casanova Jean-Laurent 
Published: April 2022

ABSTRACTPre-mRNA splicing is initiated with the recognition of a single-nucleotide intronic branchpoint (BP) within a BP motif by spliceosome elements. Fifty-six rare variants in 44 human genes have been reported to alter splicing and cause disease by disrupting BP. However, until now, no computational approach has been available to efficiently detect such variants in next-generation sequencing (NGS) data. We established a comprehensive human genome-wide BP database by integrating existing BP data, and by generating new BP data from RNA-seq of lariat debranching enzyme DBR1-mutated patients and from machine-learning predictions. We in-depth characterize multiple features of BP in major and minor introns, and find that BP and BP-2 (two-nucleotides upstream of BP) positions exhibit a lower rate of variation in human populations and higher evolutionary conservation than the intronic background, whilst being comparable to the exonic background. We develop BPHunter as a genome-wide computational approach to systematically and efficiently detect intronic variants that may disrupt BP recognition in NGS data. BPHunter retrospectively identifies 48 of the 56 known pathogenic BP mutations in which we summarize a strategy for prioritizing BP mutation candidates, and the remaining 8 all create AG dinucleotides between BP and acceptor site which is probably the reason for mis-splicing. We demonstrate the utility of BPHunter prospectively by using it to identify a novel germline heterozygous BP variant of STAT2 in a patient with critical COVID-19 pneumonia, and a novel somatic intronic 59-nucleotide deletion of ITPKB in a lymphoma patient, both of which we validate experimentally. BPHunter is publicly available from https://hgidsoft.rockefeller.edu/BPHunter and https://github.com/casanova-lab/BPHunter.
Flexible control of representational dynamics in a disinhibition-based model of decision making
Authors: Shen Bo , Louie Kenway , Glimcher Paul 
Published: April 2022

AbstractCurrent models utilize two primary circuit motifs to replicate neurobiological decision making. Recurrent gain control implements normalization-driven relative value coding, while recurrent excitation and non-selective pooled inhibition together implement winner-take-all (WTA) dynamics. Despite evidence for concurrent valuation and selection computations in individual brain regions, existing models focus selectively on either normalization or WTA dynamics and how both arise in a single circuit architecture is unknown. Here we show that a novel hybrid motif unifies both normalized representation and WTA competition, with dynamic control of circuit state governed by local disinhibition. In addition to capturing empirical psychometric and chronometric data, the model produces persistent activity consistent with working memory. Furthermore, the biological basis of disinhibition provides a simple mechanism for flexible top-down control of network states, enabling the circuit to capture diverse task-dependent neural dynamics. These results suggest a new biologically plausible mechanism for decision making and emphasize the importance of local disinhibition in neural processing.
Coisolation of peptide pairs for peptide identification and MS/MS-based quantification
Authors: Smith Ian R. , Eng Jimmy K. , Barente Anthony S. , Hogrebe Alexander , Llovet Ariadna , Rodriguez-Mias Ricard A. , Villén Judit 
Published: April 2022

ABSTRACTSILAC-based metabolic labeling is a widely adopted proteomics approach that enables quantitative comparisons among a variety of experimental conditions. Despite its quantitative capacity, SILAC experiments analyzed with data dependent acquisition (DDA) do not fully leverage peptide pair information for identification and suffer from undersampling compared to label-free proteomic experiments. Herein, we developed a data dependent acquisition strategy that coisolates and fragments SILAC peptide pairs and uses y-ions for their relative quantification. To facilitate the analysis of this type of data, we adapted the Comet sequence database search engine to make use of SILAC peptide paired fragments and developed a tool to annotate and quantify MS/MS spectra of coisolated SILAC pairs. In an initial feasibility experiment, this peptide pair coisolation approach generally improved expectation scores compared to the traditional DDA approach. Fragment ion quantification performed similarly well to precursor quantification in the MS1 and achieved more quantifications. Lastly, our method enables reliable MS/MS quantification of SILAC proteome mixtures with overlapping isotopic distributions, which are difficult to deconvolute in MS1-based quantification. This study demonstrates the initial feasibility of the coisolation approach. Coupling this approach with intelligent acquisition strategies has the potential to improve SILAC peptide sampling and quantification.
A chip-based array for high-resolution fluorescence characterization of free-standing horizontal lipid membranes under voltage clamp
Authors: Ensslen Tobias , Behrends Jan C. 
Published: April 2022

AbstractOptical techniques, such as fluorescence microscopy, are of great value in characterizing the structural dynamics of membranes and membrane proteins. A particular challenge is to combine high-resolution optical measurements with high-resolution voltage clamp electrical recordings providing direct information on e.g. single ion channel gating and/or membrane capacitance. Here, we report on a novel chip-based array device which facilitates optical access with water or oil-immersion objectives of high numerical aperture to horizontal free-standing lipid membranes while conrolling membrane voltage and recroding currents using micropatterned Ag/AgCl-electrodes. We demonstrate both wide-field and confocal imaging, as well as time-resolved single photon counting on free-standing membranes spanning sub-picoliter cavities are demonstrated while electrical signals, including single channel activity, are simultaneously acquired. This optically addressable microelectrode cavity array will allow combined electrical-optical studies of membranes and membrane proteins to be performed as a routine experiment.
An intranasal nanoparticle STING agonist has broad protective immunity against respiratory viruses and variants
Authors: Leekha Ankita , Saeedi Arash , Kumar Monish , Sefat Samiur Rahman , Martinez-Paniagua Melisa , Fathi Mohsen , Kulkarni Rohan , Biswas Sujit , Tsitoura Daphne , Liu Xinli , Cooper Laurence J.N. , Sebastian Manu , Hurst Brett L. , Varadarajan Navin 
Published: April 2022

AbstractRespiratory viral infections, especially Influenza (endemic) or SARS-CoV-2 (pandemic since 2020), cause morbidity and mortality worldwide. Despite remarkable progress in the development and deployment of vaccines, they are clearly impacted by the rapid emergence of viral variants. The development of an off-the-shelf, effective, safe, and low-cost drug for prophylaxis against respiratory viral infections is a major unmet medical need. Here, we developed NanoSTING, a liposomally encapsulated formulation of the endogenous STING agonist, 2’-3’ cGAMP, to function as an immunoantiviral. NanoSTING rapidly activates the body’s innate immune system to facilitate a broad-spectrum antiviral response against SARS-CoV-2 and influenza variants in hamsters and mice. We demonstrate that a single intranasal dose of NanoSTING can: (1) treat infections throughout the respiratory system and minimize clinical symptoms, (2) protect against highly pathogenic strains of SARS-CoV-2 (alpha and delta), (3) provide durable protection against reinfection from the same strains without the need for retreatment, (4) prevent transmission of the highly infectious SARS-CoV-2 Omicron strain, and (5) provide protection against both oseltamivir-sensitive and resistant strains of influenza. Mechanistically, administration of NanoSTING rapidly upregulated interferon-stimulated and antiviral pathways in both the nasal turbinates and lung. Our results support using NanoSTING as a thermostable, immunoantiviral with broad-spectrum antiviral properties making it appealing as a therapeutic for prophylactic or early post-exposure treatment.
Quantitative modeling demonstrates format-invariant representations of mathematical problems in the brain
Authors: Nakai Tomoya , Nishimoto Shinji 
Published: April 2022

AbstractMathematical problems can be described in either symbolic form or natural language. Previous studies have reported that activation overlaps exist for these two types of mathematical problems, but it is unclear whether they are based on similar brain representations. Furthermore, quantitative modeling of mathematical problem solving has yet to be attempted. In the present study, subjects underwent 3 h of functional magnetic resonance experiments involving math word and math expression problems, and a read word condition without any calculations was used as a control. To evaluate the brain representations of mathematical problems quantitatively, we constructed voxel-wise encoding models. Both intra- and cross-format encoding modeling significantly predicted brain activity predominantly in the left intraparietal sulcus (IPS), even after subtraction of the control condition. Representational similarity analysis and principal component analysis revealed that mathematical problems with different formats had similar cortical organization in the IPS. These findings support the idea that mathematical problems are represented in the brain in a format-invariant manner.
How to make recommendation systems fair: an adequate utility-based approach
Authors: Tansuchat Roengchai , Kosheleva Olga 
Published: April 2022

PurposeIn user-oriented websites, e.g. in news websites or in seller websites, it is important to take the user’s preferences into account when deciding which items to place in higher-exposure locations. The traditional approach to solving this problem, based on maximizing the average user utility, leads to unfair solutions, and this eventually hurts the company’s bottom line. Because of this, researchers have proposed complex schemes that explicitly add fairness to the formulation of this problem. But since utilities already describe human preferences, it is strange that it is necessary to add something beyond utilities.Design/methodology/approachIn this paper, the authors analyze the problem of selecting exposure level for different items from the viewpoint of decision theory, the basic theory underlying all our activities, including economic ones.FindingsThe authors show that a more adequate use of utilities, namely, taking into account that Nash’s bargaining solution is a proper way to make group decisions, not maximizing average utility, already leads to fair solutions.Originality/valueThe idea to apply Nash’s bargaining solution to the problem of assigning exposure level to different items is new, as well as the analysis that shows that this application restores the fairness, which is missing in the current solutions.
Incentives management among health workers in primary health-care facilities: addressing important issues in rural Ghana
Authors: Okyere Eunice , Ward Paul Russell , Marfoh Kissinger , Mwanri Lillian 
Published: April 2022

PurposeThis study seeks to explore health workers' perceptions and experiences on incentives for motivating and retaining them in primary health-care facilities in rural Ghana.Design/methodology/approach Phenomenological research design was used to explore health workers’ experiences and perceptions on their incentive packages. Sixty-eight in-depth interviews were conducted with health-care workers in primary health-care facilities and analyzed using thematic analysis approach.Findings The findings show health-care workers’ perceptions on their incentives, ranging from low awareness, unfair distribution, favoritism, means of punishment and incentives regarded unattractive. The preferred incentive packages identified were salary increase, housing availability, recognition, adequate supplies, and risk and responsibility allowances. Health-care workers suggested for the modification of incentives including vehicle importation waiver, reduction in study leave years and opportunity to pursue desired courses.Originality/value The findings suggest that incentives that align with health-care workers’ preferences can potentially improve their motivation and influence retention. Health-care workers’ concern on incentives having been used as favors and punishment as well as unfair distribution should be addressed by health managers and policymakers, to achieve the desired purpose of motivating and retaining them in rural areas. Appropriate internal monitoring mechanisms are needed for incentives regulation and to improve health workers’ retention in rural Ghana.
Validation of the psychological safety, psychological empowerment, intrapreneurial behaviour and individual performance measurements
Authors: Mahmoud Mahmoud Ahmad , Ahmad Shuhymee bin , Poespowidjojo Donny Abdul Latief 
Published: April 2022

Purpose
The purpose of this study is to assess the validity of the psychological safety (PS), psychological empowerment (PE), intrapreneurial behaviour (IB) and individual performance (IP) construct measurements originally developed in Western individualistic cultures.

Design/methodology/approach
Proportionate stratified systematic sampling was used among the production/operations middle managers in Nigerian medium enterprises (MEs), resulting in 355 valid responses. The measurements were analysed through internal consistency analysis, content, convergent and discriminant validity analysis.

Findings
The result shows that all four construct measurements are suitable and appropriate to gauge the respective constructs in collectivistic cultures such as Nigeria.

Research limitations/implications
Cross-sectional self-reported data were used to analyse the result of this study, which may lead to common method variance.

Practical implications
Organizations, especially MEs, can use the validated measurements of this study to enhance work results in the Nigerian context.

Social implications
Collectivistic cultures can benefit from the widely used measurements of PS, PE, IB and IP despite been originally developed in Western individualistic cultures.

Originality/value
This paper extends the body of knowledge by validating the measurements of PS, PE, IB and IP in collectivistic cultures such as Nigeria. Measurement validation for these constructs is scarce in this context. Thus, this study will provide a consistent and efficient reference for forthcoming studies and improve the credibility and replicability of future research results in collectivistic cultures.
Detection method for diel vertical migration pattern using 2D cross‐correlation with ADCP backscatter time‐series data
Authors: Chun Sehwa , La Hyoung Sul , Son Wuju , Kim Young Cheol , Cho Kyoung‐Ho , Yang Eun Jin 
Published: April 2022

Abstract

Diel vertical migration (DVM), which refers to the global daily migration of zooplankton and micronekton (hereafter ‘zooplankton’), serves an important function in oceanic ecosystems. DVM can be recognized as a variation in the sound scattering layer (SSL), but no standard exists for identifying SSLs, and no definition has been proposed to describe the basic features of DVM. Hence, a standardized DVM detection method is needed to report consistent results and efficiently compare the parameters over broad ocean areas and long time‐scales.

We developed an automated, quantitative method for detecting DVM and identifying the characteristic parameters using 2D cross‐correlation. We established the DVM trajectory model with linear and sinusoidal parts featuring a specific height and width. The 2D cross‐correlation method was applied to acoustic echogram images of the volume backscattering strength (Sv, dB re 1 m−1) with a synthetic image made from the DVM trajectory model. From the cross‐correlation coefficients, we found the candidate lines exhibiting the strongest possibility of being DVM trajectories.

We tested the DVM detection method on the acoustic echograms for 273 days, of which Sv was gathered by a bottom‐moored, upward‐looking acoustic Doppler current profiler (ADCP). For each identified DVM trajectory, four quantitative parameters describing their spatial and temporal structures (the maximum and minimum depths and ascent and descent times) were determined, and the existence of multi‐layer was recognized. We confirmed that this method showed better performance than the prior method based on the weighted mean depth (WMD), and as a result of visual scrutiny inspection, our method showed 88% DVM detection performance.

Our goal was to suggest a robust, quantitative, automated DVM detection method using 2D cross‐correlation. The method was successfully applied to detect DVM trajectories and define the characteristic parameters regardless of fluctuation or the multi‐layer structure due to its robustness and simple model. Analysing DVM behaviours across environments with this method could help reveal the significance of these behaviours in ocean environments.
Associations of FOXP3 gene polymorphisms with susceptibility and severity of preeclampsia: A meta‐analysis
Authors: Fan Yu‐Xin , Wu Jiang‐Hai , Yin Sun‐Jun , Zhou Tao , Huang Yan‐Hua , Meng Rui , Wang Ping , He Gong‐Hao 
Published: April 2022

AbstractObjectiveFOXP3 single nucleotide polymorphisms (SNPs) were recently elucidated to influence the development of preeclampsia (PE), but the results on this issue still remained controversial. Thus, a meta‐analysis was implemented to systematically investigate the roles of FOXP3 SNPs in PE.MethodsEligible publications were identified by retrieving relevant electronic databases. Meanwhile, the association intensity was estimated by calculating odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models.ResultsTotally eight investigations involving 3446 subjects were enrolled in the final meta‐analysis. The AC and AC + CC genotypes of FOXP3 rs3761548 were related to the susceptibility of PE in over‐dominant (OR = 1.19, 95%CI = 1.02‐1.38, P = 0.03) and recessive (OR = 0.59, 95% CI: 0.36‐0.97, P = 0.04) models. Furthermore, correlation between rs2232365 and PE was observed in recessive model (GG vs. GA + AA) (OR = 0.79, 95%CI: 0.65‐0.97, P = 0.03). Moreover, rs2232365 GA and GG + GA genotypes were associated with the severity of PE. However, rs4824747, rs3761547 and rs2280883 polymorphisms had no significant impact on PE susceptibility.ConclusionsFOXP3 rs3761548 and rs2232365 SNPs influenced the PE susceptibility and therefore may be potential biomarkers for prediction of PE risk.