bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low normal factor V enhances thrombin generation in hemophilia A by a substrate competition mechanism with factor Xa
Authors: Monroe Dougald M. , Baird Christine , Peterson Julie A. , Mast Alan E. , Manco-Johnson Marilyn , Stobb Michael , Sindi Suzanne , Fogelson Aaron L. , Leiderman Karin , Neeves Keith B. 
Published: June 2022

AbstractBleeding patterns in people with hemophilia A cannot be predicted solely by factor VIII (FVIII) levels. Some of the variance in bleeding may be attributed to differences in plasma protein composition, and specifically other coagulation factors where the normal ranges span 50-150% of the population mean. We recently used a mathematical model of thrombus formation that identified factor V (FV) levels as a strong modifier of thrombin generation in FVIII deficiencies. Counterintuitively, the model predicted low normal FV levels enhanced thrombin generation. Here, we tested this prediction and investigated its mechanism. Thrombin generation in plasma from people with FVIII deficiencies (<5%) were negatively correlated with FV levels. A substrate competition mechanism wherein FV and FVIII compete for activation by FXa during the initiation of coagulation was tested in three models: In a purified system containing only FV, FVIII, and FXa, reducing FV enhanced FVIII activation. In synthetic plasma containing the essential proteins of the extrinsic coagulation pathway, low normal FV levels resulted in enhanced thrombin generation both in the presence or absence of TFPIα. In mixture studies using FVIII-deficient human plasma immunodepleted of FV, thrombin generation was enhanced at lower levels of FV. In all models the trend was nonlinear as the effect size was significant at low, but not high, FV levels. Our data show that low normal plasma levels of FV enhance thrombin generation in hemophilia A by reducing FXa substrate competition for FVIII activation and implicate FV levels as a strong modifier of bleeding in hemophilia A.Key PointsLow normal levels of FV enhance thrombin generation in hemophilia A by reducing substate competition for FVIII activation.Plasma FV levels are a strong modifier of bleeding in hemophilia A.
High sensitivity limited material proteomics empowered by data-independent acquisition on linear ion traps
Authors: Phlairaharn Teeradon , Grégoire Samuel , Woltereck Lukas R. , Petrosius Valdemaras , Furtwängler Benjamin , Searle Brian C. , Schoof Erwin M. 
Published: June 2022

ABSTRACTIn recent years, the concept of cell heterogeneity in biology has gained increasing attention, concomitant with a push towards technologies capable of resolving such biological complexity at the molecular level. For single-cell proteomics using Mass Spectrometry (scMS) and low-input proteomics experiments, the sensitivity of an orbitrap mass analyzer can sometimes be limiting. Therefore, low-input proteomics and scMS could benefit from linear ion traps, which provide faster scanning speeds and higher sensitivity than an orbitrap mass analyzer, however at the cost of resolution. We optimized an acquisition method that combines the orbitrap and linear ion trap, as implemented on a tribrid instrument, while taking advantage of the high-field asymmetric waveform ion mobility spectrometry (FAIMS) pro interface, with a prime focus on low-input applications. First, we compared the performance of orbitrap-versus linear ion trap mass analyzers. Subsequently, we optimized critical method parameters for low-input measurement by data-independent acquisition (DIA) on the linear ion trap mass analyzer. We conclude that linear ion traps mass analyzers combined with FAIMS and Whisper™ flow chromatography are well-tailored for low-input proteomics experiments, and can simultaneously increase the throughput and sensitivity of large-scale proteomics experiments where limited material is available, such as clinical samples and cellular sub-populations.
KDR Signaling in Muscle Stem Cells Promotes Asymmetric Division and Progenitor Generation for Efficient Regeneration
Authors: Chen William , Wang Yu Xin , Ritso Morten , Perkins Theodore J. , Rudnicki Michael A. 
Published: June 2022

SUMMARYThe regulation of muscle stem cell (MuSC) asymmetric division plays an essential role in controlling the growth and repair of skeletal muscle. We discover kinase domain receptor (KDR) as a positive modulator of MuSC asymmetric division using an in-niche high-content screen and confirmed its expression in satellite cells by ddPCR and immunofluorescence. Knockdown of KDR significantly reduces the numbers of asymmetric divisions, whereas ligand stimulation of KDR increases the numbers of asymmetric divisions. KDR signaling is impaired in dystrophin-deficient satellite cells and requires a polarized cell environment established by the dystrophin glycoprotein complex (DGC) to direct asymmetric division. Mice lacking KDR in MuSCs exhibit reduced numbers of satellite cells due to precocious differentiation, and deficits in regeneration consistent with impaired asymmetric division and reduced generation of progenitors. Therefore, our experiments identify KDR signaling as playing an essential role in MuSC function in muscle regeneration.HIGHLIGHTSKDR and VEGFA are expressed in satellite cellsLigand activated KDR stimulates asymmetric satellite stem cell divisionKDR signaling requires the presence of the DGCKDR-deficient satellite cells give rise to reduced numbers of progenitorseTOC blurbChen et al., performed a chemical screen using a novel screening platform to identify modulators of muscle stem cell asymmetric division. They discovered that KDR signalling requires the presence of the dystrophin associated glycoprotein complex and is an important regulator of muscle stem cell asymmetric division.
Sem1/DSS1 accelerates ATP-dependent substrate unfolding by the proteasome through a conformation-dependent intercomplex contact
Authors: Reed Randi G. , Jobin Gabriel W. , Tomko Robert J. 
Published: June 2022

ABSTRACTThe 26S proteasome is an ∼70 subunit ATP-dependent chambered protease that destroys proteins via multiple highly coordinated processing steps. The smallest and only intrinsically disordered proteasome subunit, Sem1 (DSS1 in metazoans), is critical for efficient substrate degradation despite lacking obvious enzymatic activities and being located far away from the proteasome’s catalytic centers. Dissecting its role in proteolysis using cell-based approaches has been challenging because Sem1 also controls proteasome function indirectly via its role in proteasome biogenesis. To circumvent this challenge, we reconstituted Sem1-deficient proteasomes in vitro from purified components and systematically dissected its impact on distinct processing steps. Whereas most substrate processing steps are independent of Sem1, ATP-dependent unfolding is stimulated several-fold. Using structure-guided mutagenesis and engineered protein crosslinking, we demonstrate that Sem1 allosterically regulates ATP-dependent substrate unfolding via a distal conformation-dependent intersubunit contact. Together, this work reveals how a small, unstructured subunit comprising < 0.4% the total size of the proteasome can augment substrate processing from afar, and reveals a new allosteric pathway in controlling proteolysis.
Three-dimensional Interrogation of Cell Types and Instinctive Behavior in the Periaqueductal Gray
Authors: Vaughn Eric , Eichhorn Stephen , Jung Won , Zhuang Xiaowei , Dulac Catherine 
Published: June 2022

SummaryThe periaqueductal gray (PAG) is a critical midbrain hub that relays information from the forebrain to motor and autonomic brainstem centers to orchestrate instinctive behaviors. The current organization of the PAG into four main radial columns lacks the resolution needed to account for the vast range of PAG functions. Using spatially resolved single-cell transcriptomic measurements, we uncovered widespread transcriptional heterogeneity in the PAG with >100 excitatory and inhibitory neuronal populations, which further assemble into 19 spatial metaclusters. We explored the transcriptional and spatial logic of PAG function during instinctive behaviors and demonstrated the regional recruitment of cell types for distinct behaviors. Unexpectedly, certain behaviors trigger differential spatial activation patterns within given cell types, illustrating the complexity of PAG molecular and functional 3D organization. The newly uncovered spatial motifs and high precision cellular map of instinctive behavior in the PAG open new avenues for a mechanistic understanding of PAG function.
Mechanistic insights of glucosome condensate formation by stochastic modeling approaches
Authors: Kang Hye-Won , Nguyen Luan , An Songon , Kyoung Minjoung 
Published: June 2022

AbstractHuman liver-type phosphofructokinase 1 (PFKL) has been shown to play a scaffolder role to recruit and organize glycolytic and gluconeogenic enzymes into a multienzyme metabolic condensate, the glucosome, that regulates glucose flux in living human cells. However, it has been challenging to characterize which factors control phase separation of PFKL and so glucosome condensates in a living cell, thus hampering to understand a mechanism of reversible glucosome formation and its functional contribution to human cells. In this work, we developed a stochastic model in silico using the principal of Langevin dynamics to investigate how biological properties of PFKL contribute to the formation of glucosome condensates. Molecular dynamics simulation using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) revealed the importance of an intermolecular interaction between PFKLs, an effective concentration of PFKL at a region of interest, and a pre-organization of its own self-assembly in formation of PFKL condensates and control of their sizes. Such biological properties that define intracellular dynamics of PFKL appear to be essential for phase separation of PFKL and thus formation of glucosome condensates. Collectively, our computational study provides mechanistic insights of glucosome formation, particularly an initiation step through the formation of PFKL condensates in living human cells.
TCF4trinucleotide repeat expansions and UV irradiation increase susceptibility to ferroptosis in Fuchs endothelial corneal dystrophy
Authors: Saha Sanjib , Skeie Jessica M. , Schmidt Gregory A. , Eggleston Tim , Shevalye Hanna , Sales Christopher S. , Phruttiwanichakun Pornpoj , Dusane Apurva , Field Matthew G. , Rinkoski Tommy A. , Fautsch Michael P. , Baratz Keith H. , Roy Madhuparna , Jun Albert S. , Salem Aliasger K. , Greiner Mark A. 
Published: June 2022

ABSTRACTFuchs endothelial corneal dystrophy (FECD), the leading indication for corneal transplantation in the U.S., causes loss of corneal endothelial cells (CECs) and corneal edema leading to vision loss. FECD pathogenesis is linked to impaired response to oxidative stress and environmental ultraviolet A (UVA) exposure. Although UVA is known to cause nonapoptotic oxidative cell death resulting from iron-mediated lipid peroxidation, ferroptosis has not been characterized in FECD. We investigated the roles of genetic background and UVA exposure in causing CEC degeneration in FECD. Using ungenotyped FECD patient surgical samples, we found increased levels of cytosolic ferrous iron (Fe2+) and lipid peroxidation in end-stage diseased tissues compared with healthy controls. Using immortalized and primary cell cultures modeling theTCF4intronic trinucleotide repeat expansion genotype, we found altered gene and protein expression involved in ferroptosis compared to controls including elevated levels of Fe2+, basal lipid peroxidation, and the ferroptosis-specific marker transferrin receptor 1. Increased cytosolic Fe2+levels were detected after physiologically relevant doses of UVA exposure, indicating a role for ferroptosis in FECD disease progression. Cultured cells were more prone to ferroptosis induced by RSL3 and UVA than controls, indicating ferroptosis susceptibility is increased by both FECD genetic background and UVA. Finally, cell death was preventable after RSL3 induced ferroptosis using solubilized ubiquinol, indicating a role for anti-ferroptosis therapies in FECD. This investigation demonstrates that genetic background and UVA exposure contribute to iron-mediated lipid peroxidation and cell death in FECD, and provides the basis for future investigations of ferroptosis-mediated disease progression in FECD.
First Report of Evaluation of Variant rs11190870 nearby LBX1 Gene with Adolescent Idiopathic Scoliosis Susceptibility in a South-Asian Indian Population
Authors: Singh Hemender , Shipra  , Gupta Manish , Bhau Poorvi , Chalotra Tania , Manotra Ruchi , Gupta Nital , Gupta Geetanjali , Pandita Ajay K. , Butt Mohammad Farooq , Sharma Rajesh , Pandita Sarla , Singh Vinod , Garg Bhavuk , Rai Ekta , Sharma Swarkar 
Published: June 2022

AbstractLBX1 is a developmental gene involved in skeletal muscle development and somatosensory functioning and proven to be an important gene involved in Adolescent Idiopathic Scoliosis (AIS) etiology. Variant rs11190870 is located 7.5 kb downstream of LBX1 gene and is part of haplotype that is reported to provide risk for AIS. Several studies, including various Genome Wide Association, replication and meta-analyses studies have implicated its association with AIS in different populations. However, any such study is altogether lacking in South-Asian Indian populations. In this first genetic association study for AIS from the region, we tried to replicate association of variant rs11190870 in 95 AIS cases and 282 healthy non-AIS controls from Northwest India. The genotyping was carried out on a Realtime PCR using TaqMan allele discrimination assay and the variant was found to be following Hardy Weinberg equilibrium. The statistical analyses of the genotyping data did not show significant association (p=0.66) of variant rs11190870 with AIS in the population of Northwest India. The results are interesting findings in a population that has never been studied before for AIS susceptibility. However, the findings can be attributed to under power study thus, need evaluation in a large sample set from the population. Interestingly, frequency distribution of the variant in Indian control population datasets was found to be different than other global populations. Linkage Disequilibrium (LD) differences in the genomic region were also observed in these populations while analysing 1000Genomes phase 3 data. It hints at existence of either haplotypic differences in LBX1 locus in South-Asian Indian populations with respect to other populations or genetic heterogeneity in AIS susceptibility. This lays a foundation for genome wide association study (GWAS) in Indian populations cohort, for better understanding of AIS, a task we are pursuing.
Predicting the adoption of e-procurement in construction project delivery in Sub-Saharan Africa: an application of UTAUT2
Authors: Addy Michael Nii , Addo Evans Teye , Kwofie Titus Ebenezer , Yartey Joseph Eguei 
Published: June 2022

Purpose
The substantial benefits of e-procurement to organizations and institutions have, over the past two decades, become central to supply chain management. This study aims to identify the factors that facilitate the adoption of e-procurement system using modified Unified Theory of Acceptance and Use of Technology (UTAUT2).

Design/methodology/approach
Using a quantitative approach, the factors identified in the UTAUT2 are operationalized and examined carefully. The investigation has been conducted using a survey questionnaire. The data set has been obtained from 205 construction professionals in Ghana.

Findings
The research evinced that the decision by individuals to adopt e-procurement is mainly influenced by performance expectancy and social influence. By implication, the study found out that the respondents are more likely to adopt e-procurement if it is seen to be user-friendly and useful, and when they have a community of people supporting its use. Overall, the findings suggest that the model can stimulate a high adoption and intention to use e-procurement technologies, given its good predictive potential and robustness.

Practical implications
The structures uncovered in the study show that not all UTAUT2 factors are applicable within the study area. The findings provide a good backdrop in the development of policy and a roadmap for e-procurement implementation in Ghana. This is particularly useful for system development and implementation purposes for government agencies, contracting organizations, professionals and users of e-procurement technologies.

Originality/value
The original contribution and value of the paper is the use of UTAUT2 to provide evidence on their significance to e-procurement adoption among construction professionals.
The impact of combining work with study on the labour market performance of graduates: the joint role of work intensity and job-field match
Authors: Di Paolo Antonio , Matano Alessia 
Published: June 2022

PurposeThis paper investigates the effects of working during university education on labour market outcomes of university graduates.Design/methodology/approachBased on data from three successive cohorts of graduates from the Spanish region of Catalonia, the authors estimate the effect of having worked in different types of jobs before graduation, classified according to work intensity and the match with the field of study, on the probability of being employed, having a permanent contract or having a job that requires the specific degree four years after graduation. The authors employ a multinomial endogenous treatment model that enables controlling for self-selection into pre-graduation working activities.FindingsPre-graduation work activities that are related to the field of study are generally beneficial for employability and job stability. Work experiences unmatched with the degree's content are detrimental for graduates' job–education match.Originality/valueThis is the first paper that jointly considers the role of work intensity (part-time vs full-time) and the relationship with the field of study in a framework that accounts for self-selection into different types of jobs. The authors also contribute to the literature by estimating the effect of pre-graduation jobs not only on the chances of being employed four years after graduation but also on two important aspects of job quality: having a permanent contract and having a job that requires the specific degree.
The effect of consumers’ perception of CSR activities on their purchasing behavior: the case of the Iranian automotive market
Authors: Tahssili Nazanin , Shahhoseini Mohammad Ali 
Published: June 2022

PurposeThis study aims to examine the customer’s perception of corporate social responsibility within the automotive market in Tehran, Iran, and whether it leads to a purchasing behavior directly or indirectly through support intention.Design/methodology/approachA total of 235 customers of luxury and mid-range-priced automobiles were surveyed and analyzed using the partial least squares structural equation modeling method.FindingsRegarding luxury car owners, the authors concluded that both economical and ethical perceptions are indirectly related to purchasing behavior. Concerning mid-range-priced car buyers, both philanthropic and economical perceptions have a direct relationship with purchasing behavior, while the legal perception has an indirect relationship with purchasing behavior. The results show that Iranian car manufacturers and foreign car dealerships for both luxury and mid-range customers should focus on their economical responsibilities. The results show that luxury car manufacturers and dealerships should act ethically. With the importance of the philanthropic dimension for customers of mid-range cars, car dealerships dealing with mid-range-priced cars should focus more on their philanthropic activities. This study can help companies find better solutions to adjust their corporate social responsibility (CSR) policies to the consumers’ beliefs, gain a competitive advantage in the market and fill the knowledge gap regarding Iranian consumers.Originality/valueAlthough some research has been conducted on consumer perception and response regarding CSR in both developed and developing countries, no studies on consumer perception toward CSR have been carried out in Iran.
Forming post-COVID supply chains: does supply chain managers' social network affect resilience?
Authors: Nikookar Ethan , Yanadori Yoshio 
Published: June 2022

PurposeRethinking how to build resilience in supply chains is once again highlighted by COVID-19. Research on supply chain resilience has established flexibility as a firm-level antecedent that contributes to supply chain resilience. However, the authors know little about how supply chain flexibility is developed within a firm. Drawing on social capital theory, the authors claim that the way supply chain managers are embedded in their social networks plays a critical role in developing this antecedent. Specifically, the authors hypothesize that supply chain managers' structural and relational embeddedness in their reference network, comprised of individuals from whom they seek advice, is instrumental to developing supply chain flexibility, which subsequently enhances the firm's supply chain resilience.Design/methodology/approachSurvey data collected from 485 manufacturing firms in Australia and Hayes and Preacher's (2014) parallel multiple mediator model were employed to empirically test the hypotheses.FindingsThe findings of the study establish that supply chain managers' structural and relational embeddedness in their reference network indeed have implications for developing supply chain resilience. Furthermore, the mediator through which managers' social embeddedness influences supply chain resilience is identified in the current study.Originality/valueThe study contributes to the extant literature on supply chain resilience, investigating the role that supply chain managers' social capital play in developing the resilience of their firm.
Juridical review of law enforcement on money launderers: case study from Indonesia
Authors: Meiryani  , Warganegara Dezie Leonarda 
Published: June 2022

Purpose
Efforts to prevent and eradicate the crime of money laundering require a strong legal basis to ensure legal certainty. This paper aims to analyse law enforcement on money launderers with juridical review perspectives.

Design/methodology/approach
The research method used in this study is the statute approach, which is to examine all laws and regulations related to the crime of money laundering. The writing method used is the normative method, which is a type of research that uses the analysis of certain legislation.

Findings
Three new findings were discovered. In assessing the validity or validation of a business ownership or business transaction, there are at least three pieces of evidence that need to be used, namely, presence/absence of company/business registration in an official government database; the presence/absence (including the amount) of tax reported on income tax and VAT; and the presence/absence of other legal documents relating to the existence or general licensing of a business.

Research limitations/implications
The results of this study are also expected to be helpful for the community, government agencies, or institutions, such as the police, to combat corruption, and money laundering. The Prosecutor's Office and the Corruption Eradication Commission (KPK) describe the handling of money laundering crimes originating from money laundering crimes.

Social implications
This research can provide an overview and input for the broader community as an early warning so as not to commit money laundering crimes.

Originality/value
This is one of the pioneer studies looking into law enforcement on money launderers with comprehensive juridical review.