bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanopore molecular trajectories of a eukaryotic reverse transcriptase reveal a long-range RNA structure sensing mechanism
Authors: Shaw Alan , Craig Jonathan M. , Amiri Hossein , Kim Jeonghoon , Upton Heather E. , Pimentel Sydney C. , Huang Jesse R. , Marqusee Susan , Collins Kathleen , Gundlach Jens H. , Bustamante Carlos J. 
Published: April 2023

AbstractEukaryotic reverse transcriptases (RTs) can have essential or deleterious roles in normal human physiology and disease. Compared to well-studied helicases, it remains unclear how RTs overcome the ubiquitous RNA structural barriers during reverse transcription. Herein, we describe the development of a Mycobacterium smegmatis porin A (MspA) nanopore technique to sequence RNA to quantify the single-molecule kinetics of an RT fromBombyx moriwith single-nucleotide resolution. By establishing a quadromer map that correlates RNA sequence and MspA ion current, we were able to quantify the RT’s dwell time at every single nucleotide step along its RNA template. By challenging the enzyme with various RNA structures, we found that during cDNA synthesis the RT can sense and actively destabilize RNA structures 11-12 nt downstream of its front boundary. The ability to sequence single molecules of RNA with nanopores paves the way to investigate the single-nucleotide activity of other processive RNA translocases.
Innate attraction and aversion to odors in locusts
Authors: Ray Subhasis , Sun Kui , Stopfer Mark 
Published: April 2023

AbstractMany animals display innate preferences for some odors, but the physiological mechanisms underlying these preferences are poorly understood. Here, with behavioral tests, we establish a model system well suited to investigating olfactory mechanisms, the locustSchistocerca americana. We conducted open field two-choice tests with purely olfactory stimuli. In these tests, newly hatched locusts navigated toward, and spent time near, the source of a food odor blend, crushed wheat grass. In similar tests, we found that hatchlings avoided moderate concentrations of major individual components of the food blend odor, 1-hexanol and hexanal. They were neither attracted nor repelled by a lower concentration of 1-hexanol, but were moderately attracted to a low concentration of hexanal. These results establish that hatchlings have a strong, innate preference for food odor blend, but the valence of the blend’s individual components may be different and may change depending on the concentration. This suggests innate odor preferences may emerge from more complex processing pathways than labeled lines. Our results provide a useful entry point for an analysis of physiological mechanisms underlying innate sensory preferences.
Dehydrated snakes reduce postprandial thermophily
Authors: Azzolini Jill L. , Roderick Travis B. , DeNardo Dale F. 
Published: April 2023

AbstractTransient thermophily in ectothermic animals is a common response during substantive physiological events. For example, ectotherms often elevate body temperature after ingesting a meal. In particular, the increase in metabolism during the postprandial period of pythons - known as specific dynamic action – is supported by a concurrent increase in preferred temperature. The objective of this study was to determine whether hydration state influenced digestion-related behavioral thermophily. Sixteen (8 male and 8 female) Children’s pythons (Antaresia childreni) with surgically implanted temperature data loggers were housed individually and provided a thermal gradient of 25-45 °C. Body temperature was recorded hourly beginning 6 days prior to feeding and for 18 days post-feeding, thus covering pre-feeding, postprandial, and post-absorptive stages. Each snake underwent this 24-day trial twice, once when hydrated and once when dehydrated. Our results revealed a significant interaction between temperature preference, digestive stage, and hydration state. Under both hydrated and dehydrated conditions, snakes similarly increased their body temperature shortly after consuming a meal, but during the later period of the postprandial stage, snakes selected significantly lower (~1.5°C) body temperature when they were dehydrated compared to when they were hydrated. Our results demonstrate a significant effect of hydration state on postprandial thermophily, but the impact of this dehydration-induced temperature reduction on digestive physiology (e.g., passage time, energy assimilation) is unknown and warrants further study.Summary statementDehydration suppresses the extent to which python increase body temperature after ingesting a meal, thus demonstrating a physiological conflict between optimizing body temperature and water balance.
Polarized vesicle transport requires AP-1-mediated recruitment of KIF13A and KIF13B at the trans-Golgi network
Authors: Montgomery Andrew C. , Mendoza Christina S. , Garbouchian Alex , Quinones Geraldine B. , Bentley Marvin 
Published: April 2023

ABSTRACTNeurons are polarized cells that require accurate membrane trafficking to maintain distinct protein complements at dendritic and axonal membranes. The Kinesin-3 family members KIF13A and KIF13B are thought to mediate dendrite-selective transport, but the mechanism by which they are recruited to polarized vesicles and the differences in the specific trafficking role of each KIF13 have not been defined. We performed live-cell imaging in cultured hippocampal neurons and found that KIF13A is a dedicated dendrite-selective kinesin. KIF13B confers two different transport modes, both dendrite- and axon-selective transport. Both KIF13s are maintained at the trans-Golgi network by interactions with the heterotetrameric adaptor protein complex AP-1. Interference with KIF13 binding to AP-1 resulted in disruptions to both dendrite- and axon- selective trafficking. We conclude that AP-1 is the molecular link between the sorting of polarized cargoes into vesicles and the recruitment of kinesins that confer polarized transport.
Cross-talk between QseBC and PmrAB two-component systems is crucial for regulation of motility and colistin resistance in EnteropathogenicEscherichia coli
Authors: Fernandez-Ciruelos Blanca , Potmis Tasneemah , Solomin Vitalii , Wells Jerry M. 
Published: April 2023

AbstractThe quorum sensing two-component system (TCS) QseBC has been linked to virulence, motility and metabolism regulation in multiple Gram-negative pathogens, including EnterohaemorrhagicEscherichia coli(EHEC), UropathogenicE. coli(UPEC) andSalmonella enterica.In EHEC, the sensor histidine kinase (HK) QseC detects the quorum sensing signalling molecule AI-3 and also acts as an adrenergic sensor binding host epinephrine and norepinephrine. Downstream changes in gene expression are mediated by phosphorylation of its cognate response regulator (RR) QseB, and ʻcross-talk’ with non-cognate regulators KdpE and QseF to activate motility and virulence. In UPEC, cross-talk between QseBC and TCS PmrAB is crucial in the regulation and phosphorylation of QseB RR that acts as a repressor of multiple pathways, including motility. Here, we investigated QseBC regulation of motility in the atypical EnteropathogenicE. coli(EPEC) strain O125ac:H6, causative agent of persistent diarrhoea in children, and its possible cross-talk with the KdpDE and PmrAB TCS. We showed that in EPEC QseB acts as a repressor of genes involved in motility, virulence and stress response, and in absence of QseC HK, QseB is activated by the non-cognate PmrB HK, similarly to UPEC. We show that in absence of QseC, phosphorylated QseB activates its own expression, and is responsible for the low motility phenotypes seen in a QseC deletion mutant. Furthermore, we showed that KdpD HK regulates motility in an independent manner to QseBC and through a third unidentified party different to its own response regulator KdpE. We showed that PmrAB has a role in iron adaptation independent to QseBC. Finally, we showed that QseB is the responsible for activation of colistin and polymyxin B resistance genes while PmrA RR acts by preventing QseB binding to the promoter of polymyxin resistance genes.Author summaryEnteropathogenicEscherichia coli(EPEC) is a human pathogen and the leading cause of diarrhoea in children under 5 years in low-income countries. EPEC, and specially the subgroup denominated atypical EPEC, has been associated with community-acquired persistent diarrhoea and also is an important agent of post-weaning diarrhoea in young piglets. Two-component systems (TCS) are signalling system used by bacteria to sense and adapt to different stimuli. Bacteria use TCS to detect host signals as queues to exert virulence in their preferred niche. QseBC is a TCS that has been linked to regulation of motility and virulence in other pathogenicE. coli.In this study we broaden our understanding of QseBC TCS and its role in regulating virulence traits such as motility in atypical EPEC. We also investigate its capabilities to interact with other TCS, named KdpDE and PmrAB, and how these interactions are responsible for regulation of motility and resistance to antimicrobials such as colistin.
Insights into the ISG15 transfer cascade by the UBE1L activating enzyme
Authors: Wallace Iona , Baek Kheewoong , Prabu Jesuraj R. , Vollrath Ronnald , von Gronau Susanne , Schulman Brenda A. , Swatek Kirby N. 
Published: April 2023

AbstractThe attachment of the ubiquitin-like protein ISG15 to substrates is a well-established antiviral signalling mechanism of the innate immune response. However, despite the identification of thousands of substrates and clear roles in antiviral immunity, a molecular understanding of ISG15 selection and transfer through its cognate E1-E2- E3 enzyme cascade is largely unknown. Here, we present a 3.45 Å cryo-EM structure of a chemically trapped UBE1L-UBE2L6 complex bound to activated ISG15. This structure reveals the details of the first steps of ISG15 recognition and UBE2L6 recruitment by UBE1L. Taking advantage of viral effector proteins from severe acute respiratory coronavirus 2 (SARS-CoV-2) and influenza B virus (IBV), we validated the structure and confirmed the importance of the ISG15 C-terminal ubiquitin-like domain in the adenylation reaction. Moreover, biochemical characterization of the UBE1L-ISG15 and UBE1L-UBE2L6 interactions enabled the design of ISG15 and UBE2L6 mutants with altered selectively for the ISG15 and ubiquitin conjugation pathways. Together, our study provides much needed insight into the specificity determinants that ensure the fidelity of ISG15 signalling during the antiviral response.
Interaction studies of Gut metabolite; Trimethylene amine Oxide with Bovine Serum Albumin through Spectroscopic, DFT and Molecular Docking Approach
Authors: Verma Awadhesh Kumar , Gulati Payal , Lakshmi GBVS , Solanki Pratima R , Kumar Anil 
Published: April 2023

AbstractTrimethyleneamine N-oxide (TMAO); a gut microbiota derived metabolite has been involved in human health and diseases. It is enhanced by insulin resistivity and linked with various metabolic syndromes in human being such as renal, neuro-degenerative, and cardiovascular diseases. The primary mechanism through which TMAOs promotes disease is not clear yet. TMAO with MW= 75.11 g/mol is a small biomolecule hence, it becomes crucial to develop the conjugate of TMAO with BSA for aptamer synthesis. The binding interactions among TMAO and BSA were investigated using spectroscopic methods like UV-Vis, photoluminescence, Fourier transform infrared and circular dichroism. Hydrophilicity/Hydrophobicity of the conjugate was monitored by using contact angle (Ɵ) measurement. Sodium dodecyl sulphate polyacryl amide gel electrophoresis (SDS-PAGE) confirmed the different ratio of conjugate formation with the help of band size. This interaction study reveals that TMAO bind with BSA on two sites and with high affinity on one site. Docking studies also showed TMAO is involved in non-covalent interaction with bovine serum albumin forming stable docking complex with binding score of –3.6 kcal/mol obtained from the docking simulation. TMAO is involved in interaction with BSA via amino acid residues forming the stable docking complex through hydrogen bond and electrostatic interaction. This kind of interaction study may be helpful in making strategies to break the conjugation between serum albumin and uremic toxin and pave the way for the treatment for CKD and other diseases wherein TMAO is implicated. Also, conjugation of TMAO and BSA studied here may also serve as premise to develop aptamers for the detection of TMAO in the body fluids.
The BOD1L subunit of the mammalian SETD1A complex sustains the expression of DNA damage repair genes despite restraining H3K4 trimethylation
Authors: Ciotta Giovanni , Singh Sukhdeep , Gupta Ashish , Torres Davi Coe , Fu Jun , Choudhury Rupam , Chu Wai Kit , Choudhary Chuna , Gahurova Lenka , Al-Fatlawi Ali , Schroeder Michael , Aasland Rein , Poetsch Anna R. , Anastassiadis Konstantinos , Stewart A. Francis 
Published: April 2023

AbstractSETD1A is the histone 3 lysine 4 (H3K4) methyltransferase central to the mammalian version of the highly conserved eight subunit Set1 complex (Set1C) that apparently conveys H3K4 trimethylation (H3K4me3) onto all active Pol II promoters. Accordingly, mouse embryonic stem cells (ESCs) die when SETD1A is removed. We report that death is accompanied by loss of expression of DNA repair genes and accumulating DNA damage. BOD1L and BOD1 are homologs of the yeast Set1C subunit, Shg1, and subunits of the mammalian SETD1A and B complexes. We show that the Shg1 homology region binds to a highly conserved central α-helix in SETD1A and B. Like mutagenesis ofShg1in yeast, conditional mutagenesis ofBod1lin ESCs promoted increased H3K4 di- and tri-methylation but also, like loss of SETD1A, loss of expression of DNA repair genes, increased DNA damage and cell death. In contrast to similar losses of gene expression, the converse changes in H3K4 methylation implies that H3K4 methylation is not essential for expression of the DNA repair network genes. Because BOD1L becomes highly phosphorylated after DNA damage and acts to protect damaged replication forks, the SETD1A complex and BOD1L in particular are key nodes for the DNA damage repair network.
StocSum: stochastic summary statistics for whole genome sequencing studies
Authors: Wang Nannan , Yu Bing , Jun Goo , Qi Qibin , Durazo-Arvizu Ramon A. , Lindstrom Sara , Morrison Alanna C. , Kaplan Robert C. , Boerwinkle Eric , Chen Han 
Published: April 2023

AbstractGenomic summary statistics, usually defined as single-variant test results from genome-wide association studies, have been widely used to advance the genetics field in a wide range of applications. Applications that involve multiple genetic variants also require their correlations or linkage disequilibrium (LD) information, often obtained from an external reference panel. In practice, it is usually difficult to find suitable external reference panels that represent the LD structure for underrepresented and admixed populations, or rare genetic variants from whole genome sequencing (WGS) studies, limiting the scope of applications for genomic summary statistics. Here we introduce StocSum, a novel reference-panel-free statistical framework for generating, managing, and analyzing stochastic summary statistics using random vectors. We develop various downstream applications using StocSum including single-variant tests, conditional association tests, gene-environment interaction tests, variant set tests, as well as meta-analysis and LD score regression tools. We demonstrate the accuracy and computational efficiency of StocSum using two cohorts from the Trans-Omics for Precision Medicine Program. StocSum will facilitate sharing and utilization of genomic summary statistics from WGS studies, especially for underrepresented and admixed populations.
What do consumers care about when purchasing experiential packaging?
Authors: Álvarez-González Paula , Dopico-Parada Ana , López-Miguens María J. 
Published: April 2023

PurposeThe importance of packaging attributes for purchase decisions has generated interest in the research and food industry. As a matter of fact, innovation in packaging is constantly searching for new solutions that generate customer experience. The aim of this study is to analyse the effect of packaging attributes (protection, convenience, portability and storage, information, sustainability, branding and engagement) on consumer purchase intention of experiential packaging especially designed to provide an extraordinary sensory or interactive communicational experience and the influence of potential moderators.Design/methodology/approachThe authors used a quantitative methodology based on the partial least squares (PLS) technique to estimate the structural model proposed. A purposely developed questionnaire was administered to a non-probabilistic sample of 1,489 European consumers. The questionnaire included questions related to consumers' perception of packaging attributes and purchase intention of different experiential packages.FindingsThe results indicate that packaging attributes are related to consumer purchase intention of experiential packaging. Engagement attributes show the strongest positive influence followed by branding and economy. However, attributes such as sustainability showed a negative effect on the purchase intention of these packages. The authors’ results also show the influence of gender, family structure and residential background as moderators of the relationships.Originality/valueCustomers' decision-making processes are strongly influenced by product packaging. However, little is known about how new technologies and design in packaging influence consumers' responses. This research provides evidence of the influence of packaging attributes on consumer purchase intention for experiential packaging, a proliferating area of research.
Expatriation and repatriation as one integrated process: the roles of developmental assignments, repatriate turnover, employee willingness for expatriation and repatriation support practices
Authors: Wang Chun-Hsiao 
Published: April 2023

PurposeThis paper aims to integrate the perspectives of expatriation and repatriation not as two unrelated stages but rather as one integrated process.Design/methodology/approachA sample comprising 94 human resource (HR) representatives from large Taiwanese multinational corporations (MNCs) provided objective data on the organizational expatriate/repatriate practices.FindingsThe use of developmental assignments was positively related to organizational repatriate turnover, but such a positive relationship was significant only when MNCs used low levels of repatriation support practices. Organizational repatriate turnover was negatively related to employee willingness for expatriation and the use of developmental assignments increased employee willingness for expatriation. Organizational repatriate turnover was a competitive mediator between the use of developmental assignments and employee willingness for expatriation. Moreover, organizational repatriate turnover mediated the relationship when MNCs used low levels of repatriation support practices, but not when MNCs used high levels of repatriation support practices.Practical implicationsMNCs should ensure the use of development assignments is matched with high levels of repatriation support practices and treat expatriation and repatriation management as one integrated process.Originality/valueAs the world economy becomes more integrated, MNCs are increasingly challenged in their efforts to send employees abroad on expatriate assignments that are developmental by design, to reduce organizational repatriate turnover and to increase employee willingness for expatriation. However, there is a lack of understanding about how they are all linked.
Digital leadership enactment in the construction industry: barriers undermining effective transformation
Authors: Zulu Sambo Lyson , Saad Ali M. , Ajayi Saheed O. , Dulaimi Mohammed , Unuigbe Maria 
Published: April 2023

PurposeIn the past decade, transforming key processes and activities towards a more digital nature has been the focus of most industries to exploit the associated advantages. Despite that, organisations in the construction sector are lagging the list of early adopters. The slow rate of a fundamental digital transformation is being linked to the challenges facing an effective leadership. The purpose of this paper is, therefore, to shed light on the barriers to digital leadership enactment in the construction industry. Limited research has empirically analysed and discussed these barriers to explain the low transformation rate in the existing body of knowledge.Design/methodology/approachThis paper empirically investigates the perspectives of construction industry professionals acquiring various roles in the industry. This study captured the views of 38 participants, adopting a qualitative methodological approach to detail the barriers and explain the slow digital transformation rate.FindingsFindings are grouped into five themes: leadership characteristics, management and organisational issues, resource constraints, technological issues and risk perceptions. The findings are helpful to business leaders, researchers, trainers and educators to develop measures to encourage leaders in the industry to be at the forefront of digital transformation in their organisations.Originality/valueLiterature, however, is discreet in reflecting the challenges and barriers facing today's leadership in facilitating digital transformation among construction stakeholders. This paper provides insights into the variables that may be undermining wider digital adoption across the construction sector's organisations.
Understanding the difference between opportunistic and needy customers’ borrowing behavior: a new approach to segment current credit card customers
Authors: Kasaian Keyvan , Murthi B.P.S. , Steffes Erin 
Published: April 2023

PurposeThe authors offer a new approach to segment credit card customers by classifying customers into two unobserved (latent) segments: opportunistic and needy.Design/methodology/approachThe authors develop a finite mixture model to estimate customers’ tendency to borrow using the three alternatives available to them—promotional cash advances, regular cash advances and retail balances.FindingsThe results support the presence of at least two segments among credit card customers. The authors find that relative to opportunistic individuals, needy customers are typically more sensitive to interest rates. Additionally, the results indicate that offering promotional cash advances to current credit card customers increases their sensitivity to regular interest rates. Furthermore, the findings indicate that needy customers tend to have a higher stickiness in their debt. In the post-estimation analyses, the authors observe that needy customers generate more revenue than opportunistic customers. Interestingly, the bank does not perform well in targeting needy individuals and targets both groups with the same probability.Originality/valueThe authors argue that teaser rates attract at least two segments of borrowers—the “needy” segment, which is more likely to be cash-strapped, and the “opportunistic” segment, which looks at these teaser rates as an opportunity. However, banks do not observe segment membership. Hence, the authors offer a new approach to identifying these segments and show that understanding the behavior of these latent segments could help a bank target profitable customers more effectively.