bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging Synthetic Virology for the Rapid Engineering of Vesicular Stomatitis Virus (VSV)
Authors: Moles Chad M. , Basu Rupsa , Weijmarshausen Peter , Ho Brenda , Farhat Manal , Flaat Taylor , Smith Bruce F. 
Published: September 2024

AbstractVesicular stomatitis virus (VSV) is a prototype RNA virus that has been instrumental in advancing our understanding of viral molecular biology and has applications in vaccine development, cancer therapy, antiviral screening, and more. Current VSV genome plasmids for purchase or contract virus services provide limited options for modification, restricted to predefined cloning sites and insert locations. Improved methods and tools to engineer VSV will unlock further insights in long-standing virology questions and new opportunities for innovative therapies. Here, we report the design and construction of a full-length VSV genome. The 11,161 base pair synthetic VSV (synVSV) was assembled from four modularized DNA fragments. Following rescue and titration, phenotypic analysis showed no significant differences between natural and synthetic viruses. To demonstrate the utility of a synthetic virology platform, we then engineered VSV with a foreign glycoprotein, a common use case for studying viral entry and developing anti-virals. To show the freedom-of-design afforded by this platform, we then modified the genome of VSV by rearranging the gene order, switching the positions of VSV-P and VSV-M genes. This work represents a significant technical advance, providing a flexible, cost-efficient platform for the rapid construction of VSV genomes, facilitating the development of innovative therapies.
Combined PARP14 Inhibition and PD-1 Blockade Promotes Cytotoxic T Cell Quiescence and Modulates Macrophage Polarization in Relapsed Melanoma
Authors: Leshem Rotem , Sefton Kieran N. , Wong Chun Wai , Lin I-Hsuan , Isaac Dervla T. , Niepel Mario , Hurlstone Adam F.L. 
Published: September 2024

AbstractProgrammed Cell Death 1 (PD-1) signaling blockade effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ) -driven immune homeostatic mechanisms in melanoma cells contribute to immune evasion and acquired resistance. We previously demonstrated that poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, in part mediates IFNγ-driven resistance, as its inhibition prolonged PD-1 blockade responses in preclinical models. Nevertheless, PARP14 inhibition alone could not achieve full tumor clearance, indicating additional resistance mechanisms. Herein, we identify a robust PARP14 catalytic inhibitor (PARP14i) gene signature associated with improved patient survival. We elucidate immune and tumor cell adaptations to PARP14 inhibition combined with PD-1 blockade using preclinical models. This combination therapy suppressed tumor-associated macrophages while increasing pro-inflammatory memory macrophages. Notably, it preserved cytotoxic T cell function by inducing a quiescent state, mitigating terminal exhaustion. Despite enhancing immune responses, adaptive resistance mechanisms emerged in tumor cells, engaging alternative immune evasion pathways. These findings indicate that this combination therapy primes immune cells for further therapeutic intervention, providing a promising strategy to overcome resistance and optimize treatment outcomes.SummaryWhile immune checkpoint inhibitors, such as α-PD-1 therapy, provide significant clinical benefits, many tumors develop resistance and relapse. Re-treatment with α-PD-1 often fails because T cells lose their function (a process called exhaustion), and immune-suppressing cells like tumor-associated macrophages (TAMs) increase in the tumor environment, enabling tumors to evade immune attack.Recent studies have shown that a small molecule inhibitor of PARP14 can restore sensitivity to α-PD-1 therapy by remodeling the tumor environment. This includes increasing immune cell infiltration and improving antigen presentation, which helps the immune system recognize tumor cells.Using single-cell RNA sequencing, we discovered that this therapy induces a new state of T cell dormancy, where cytotoxic T cells temporarily stop attacking but retain the potential to be reactivated by additional treatments. This finding opens new opportunities to sustain immune responses and improve outcomes for patients who relapse after immunotherapy.Graphical Summary
Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer’s disease identifies cognitive status
Authors: Madrid Andy , Papale Ligia A. , Bergmann Phillip E. , Breen Coleman , Clark Lindsay R. , Asthana Sanjay , Johnson Sterling C. , Keleş Sündüz , Hogan Kirk J. , Alisch Reid S. 
Published: September 2024

AbstractINTRODUCTIONWhole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer’s disease (AD) but has not been tested in persons with mild cognitive impairment (MCI).METHODSWe used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU).RESULTSWGMS identified 9,756 differentially methylated positions (DMPs) in persons with MCI, including 1,743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport. 447 DMPs exhibit progressively increasing or decreasing DNA methylation levels between CU, MCI, and AD that correspond to cognitive status.DISCUSSIONWGMS identifies DMPs in known and newly detected genes in blood from persons with MCI and AD that support blood DNA methylation levels as candidate biomarkers of cognitive status.
Assessing neurocognitive maturation in early adolescence based on baby and adult functional brain landscapes
Authors: Kardan Omid , Jones Natasha , Wheelock Muriah D. , Michael Cleanthis , Angstadt Mike , Molloy M. Fiona , Cope Lora M. , Martz Meghan M. , McCurry Katherine L. , Hardee Jillian E. , Rosenberg Monica D. , Weigard Alexander S. , Hyde Luke W. , Sripada Chandra , Heitzeg Mary M. 
Published: September 2024

AbstractAdolescence is a period of growth in cognitive performance and functioning. Recently, data-driven measures of brain-age gap, which can index cognitive decline in older populations, have been utilized in adolescent data with mixed findings. Instead of using a data-driven approach, here we assess the maturation status of the brain functional landscape in early adolescence by directly comparing an individual’s resting-state functional connectivity (rsFC) to the canonical early-life and adulthood communities. Specifically, we hypothesized that the degree to which a youth’s connectome is better captured by adult networks compared to infant/toddler networks is predictive of their cognitive development. To test this hypothesis across individuals and longitudinally, we utilized the Adolescent Brain Cognitive Development (ABCD) Study at baseline (9-10 years; n = 6,489) and 2-year-follow-up (Y2: 11-12 years; n = 5,089). Adjusted for demographic factors, our anchored rsFC score (AFC) was associated with better task performance both across and within participants. AFC was related to age and aging across youth, and change in AFC statistically mediated the age-related change in task performance. In conclusion, we showed that a model-fitting-free index of the brain at rest that is anchored to both adult and baby connectivity landscapes predicts cognitive performance and development in youth.
Occurrence of “under-the-radar” antibiotic resistance in anthropogenically affected produce
Authors: Davidovich Chagai , Erokhina Kseniia , Gupta Chhedi Lal , Zhu Yong-Guan , Su Jian-Qiang , Djordjevic Steven P. , Wyrsch Ethan R. , Blum Shlomo , Cytryn Eddie 
Published: September 2024

AbstractWith global climate change, treated-wastewater (TWW) irrigation and manure amendment are becoming increasingly important in sustainable agriculture in water- and nutrient-stressed regions. Yet, these practices can potentially disseminate pathogens and antimicrobial resistance (AMR) determinants to crops, resulting in serious health risks to humans through the food chain. Previous studies demonstrated that pathogen and AMR indicators from wastewater and manure survive poorly in the environment, suggesting that ecological barriers prevent their dissemination. However, we recently found that these elements can persist below detection levels in low quality TWW-irrigated soil, and potentially proliferate under favorable conditions. This “under the radar” phenomenon was further investigated here, in TWW irrigated- and poultry litter-amended lettuce plants, using an enrichment platform that resembles gut conditions, and an analytical approach that combined molecular and cultivation-based techniques. Enrichment uncovered clinically-relevant multidrug resistant pathogen indicators and a myriad of antibiotic resistance genes in the litter amended and TWW-irrigated lettuce that were not detected by direct analyses, or in the enriched freshwater irrigated samples. Selected resistantE. coliisolates were capable of horizontally transferring plasmids carrying multiple resistance genes to a susceptible strain. Overall, our study underlines the hidden risks of under-the-radar pathogen and AMR determinants in anthropogenically affected agroenvironments, providing a novel platform to improve quantitative microbial risk assessment models in the future.
Capture, mutual inhibition and release mechanism for aPKC-Par6 and its multi-site polarity substrate Lgl
Authors: Earl Christopher P. , Cobbaut Mathias , Barros-Carvalho André , Ivanova Marina E. , Briggs David C. , Morais-de-Sá Eurico , Parker Peter J. , McDonald Neil Q. 
Published: September 2024

AbstractThe mutually antagonistic kinase-substrate relationship between the apical aPKC-Par6 heterodimer and the basolateral substrate Lgl is key to the establishment and maintenance of cell polarity across metazoa. Although aPKC-Par6 can phosphorylate Lgl at three serine sites to exclude it from the apical domain, paradoxically, aPKC-Par6 and Lgl can also form a stable kinase-substrate complex whose function remains unclear and with conflicting roles proposed for Par6. We report the structure of human aPKCι-Par6α bound to full-length Llgl1, captured through an aPKCι docking site and a Par6PDZcontact. This soluble tripartite complex traps a phospho-S663 Llgl1 intermediate bridging between aPKC and Par6, impeding phosphorylation progression. Thus, aPKCι is effectively inhibited by Llgl1pS663whilst Llgl1 is captured by aPKCι-Par6. Mutational disruption of Lgl-aPKC interaction impedes complex assembly and Lgl phosphorylation, whereas disrupting the Lgl-Par6PDZcontact promotes complex dissociation and completion of Lgl phosphorylation cycle. We incorporate these findings into a Par6PDZ-regulated substrate capture-and-release model that we demonstrate requires binding by Cdc42-GTP and the apical partner Crumbs to drive complex disassembly. Our results provide an explanation for the opposing roles of Par6 underpinning the spatial control of aPKC-Par6 activity by Lgl relevant to polarised membrane contexts across multi-cellular organisms.
Biosynthesis of the α-D-Mannosidase Inhibitor (–)-Swainsonine
Authors: Liu Shaonan , Batool Zainab , Hai Yang 
Published: September 2024

Abstract(–)-Swainsonine is a polyhydroxylated indolizidine alkaloid with potent inhibitory activity against α-D-mannosidases. In this work, we successfully reconstituted swainsonine biosynthetic pathway both in vivo and in vitro. Our study unveiled an unexpected epimerization mechanism involving two α-ketoglutarate-dependent non-heme iron dioxygenases (SwnH2 and SwnH1), and an unusual imine reductase (SwnN), which displays substrate-dependent stereospecificity. The stereochemical outcome of SwnN-catalyzed iminium reduction is ultimately dictated by SwnH1-catalyzed C8-hydroxylation. We also serendipitously discovered that anO-acetyl group can serve as a detachable protecting/directing group, altering the site-selectivity of SwnH2-catalyzed hydroxylation while maintaining the stereoselectivity. Insights gained from the biochemical characterization of these tailoring enzymes enabled biocatalytic synthesis of a new polyhydroxylated indolizidine alkaloid, opening doors to the biosynthesis of diverse natural product-based glycosidase inhibitors.
Ballistic and delayed photodissociation channels in the
B̃ 2A11
state of water studied with resonant inelastic x-ray scattering
Authors: Ignatova Nina , Kimberg Victor , Gel'mukhanov Faris , Pietzsch Annette , Eckert Sebastian , Fondell Mattis , Kennedy Brian , Dantz Marcus , Schmitt Thorsten , Odelius Michael , Föhlisch Alexander , Vaz da Cruz Vinícius 
Published: September 2024

Photodissociation is one of the most important photoinduced chemical reactions. It occurs when the potential energy curve along a chemical bond is repulsive in an excited state. Typically, “ballistic” ultrafast dissociation leads to the broadening of absorption resonances and the smearing out of vibrational fine-structure. We report on the photodissociation of H2O in the B̃ 2A11 electronic state, characterized by a |3a1−14a11〉 configuration, which can be reached via resonant inelastic x-ray scattering or direct ultraviolet absorption. In both cases the spectra show narrow vibrational resonances, in spite of the dissociative character of the state. We find that “delayed” dissociation pathways, caused by reflection of the nuclear wave packet, are responsible for this effect. In spite of the analogous topology of the potential energy surfaces of the core- and valence-excited states, the reflection of the wave packet takes place only in the latter. The two-dimensional wave packet of the O-H stretching coordinates becomes trapped in a “cavity” near the Franck-Condon region, resulting from a mismatch between the OH vibrational frequency in the cavity and the one at the dissociation limit.

Published by the American Physical Society
2024
Differentiation in perceived organizational support and knowledge sharing of outsourced employees – a cross-hierarchy moderating model
Authors: Qin Chuanyan , Wang Pengcheng , Liu Shanshi 
Published: September 2024

PurposeOutsourcing has become a crucial avenue for companies to acquire external knowledge. To better understand how dual organizational supports influence the knowledge sharing behavior of outsourced employees within triangular employment relationships, grounded in social exchange theory, this study explores the effect and mechanism of differentiation in perceived organizational support (DPOS) on knowledge sharing of outsourced employees.Design/methodology/approachA two-wave survey was conducted to test the hypotheses, and data were collected from 271 outsourced employees and their leaders (from client organizations) in 52 interorganizational teams.FindingsResults show that DPOS positively affect the knowledge sharing of outsourced employees and has a stronger predictive value than that of client organizational support. Outsourced employees’ psychological ownership to the interorganizational team mediates this relationship. Task interdependence plays a positive cross-hierarchy moderating role in the relationship between DPOS and psychological ownership to the interorganizational team.Practical implicationsThis research provides practical advice for support strategies of client and supplier organizations.Originality/valueResults provide further understanding for outsourced employees’ psychological and behavioral mode in triangular employment contexts.
Analysis of efficient discretization technique for nonlinear integral equations of Hammerstein type
Authors: Bhat Imtiyaz Ahmad , Mishra Lakshmi Narayan , Mishra Vishnu Narayan , Tunç Cemil 
Published: September 2024

Purpose
This study focuses on investigating the numerical solution of second-kind nonlinear Volterra–Fredholm–Hammerstein integral equations (NVFHIEs) by discretization technique. The purpose of this paper is to develop an efficient and accurate method for solving NVFHIEs, which are crucial for modeling systems with memory and cumulative effects, integrating past and present influences with nonlinear interactions. They are widely applied in control theory, population dynamics and physics. These equations are essential for solving complex real-world problems.

Design/methodology/approach
Demonstrating the solution’s existence and uniqueness in the equation is accomplished by using the Picard iterative method as a key technique. Using the trapezoidal discretization method is the chosen approach for numerically approximating the solution, yielding a nonlinear system of algebraic equations. The trapezoidal method (TM) exhibits quadratic convergence to the solution, supported by the application of a discrete Grönwall inequality. A novel Grönwall inequality is introduced to demonstrate the convergence of the considered method. This approach enables a detailed analysis of the equation’s behavior and facilitates the development of a robust solution method.

Findings
The numerical results conclusively show that the proposed method is highly efficacious in solving NVFHIEs, significantly reducing computational effort. Numerical examples and comparisons underscore the method’s practicality, effectiveness and reliability, confirming its outstanding performance compared to the referenced method.

Originality/value
Unlike existing approaches that rely on a combination of methods to tackle different aspects of the complex problems, especially nonlinear integral equations, the current approach presents a significant single-method solution, providing a comprehensive approach to solving the entire problem. Furthermore, the present work introduces the first numerical approaches for the considered integral equation, which has not been previously explored in the existing literature. To the best of the authors’ knowledge, the work is the first to address this equation, providing a foundational contribution for future research and applications. This innovative strategy not only simplifies the computational process but also offers a more comprehensive understanding of the problem’s dynamics.
Lesson study in Content and Language Integrated Learning: making young case pupils’ learning visible through English alongside translanguaging and trans-semiotising
Authors: Frank Schmid Silvia 
Published: September 2024

PurposeThe paper reports how lesson study helped to make the learning of students with limited English competencies visible in Content and Language Integrated Learning (CLIL).Design/methodology/approachThe two lesson study cycles took place in a Swiss primary school with a focus on three case pupils each with heterogeneous attainment levels in English. The research group observed how the case pupils coped with learning English integrated with art, crafts, and sports in four research lessons. Following a case study methodology, the research focussed on how the case pupils used their limited English language competencies complemented with multilingual and multimodal means to make their learning visible.FindingsThanks to the close observations of students’ learning and the detailed analysis thereof as a cooperative effort of the research group, the lesson study revealed that the case pupils used varied means to express their learning partly depending on their levels of English.Research limitations/implicationsThis small-scale case study only describes data collected from four research lessons based on a total of 12 case pupils.Originality/valueCommonly during lesson study, the students’ learning is captured through the verbal language they use. But if the research lesson takes place in a foreign language setting in which students’ language competencies are limited in expressing their learning, other languages and modes of communication must be considered. To date, there are few papers on how lesson study helps to explore learners’ use of so-called translanguaging and trans-semiotising.
Moderation of OM practice effectiveness by organizational culture profile: contingency vs paradox perspective
Authors: Bortolotti Thomas , Boscari Stefania , Danese Pamela , Flynn Barbara Bechler 
Published: September 2024

PurposeThis paper investigates how a firm’s organizational culture profile (configuration of organizational culture types) influences the effectiveness of operations management (OM) practices in improving their targeted outcomes.Design/methodology/approachWe developed alternative hypotheses based on contingency and paradox perspectives to predict the effectiveness of OM practices in dominant (one prevalent organizational culture type) vs eclectic (opposing organizational culture types at a similar level) organizational culture profiles. They were tested using data from over 7,000 respondents across 330 manufacturing plants in 15 countries.FindingsConsistent with contingency theory, OM practices oriented toward innovation are more efficacious in plants with an adhocracy-dominant organizational culture profile and practices targeting supply chain (SC) control are less effective in a clan-dominant organizational culture profile. Consistent with paradox theory, OM practices oriented toward efficiency or SC control are more effective in plants with an eclectic organizational culture profile.Practical implicationsThis study offers relevant practical implications regarding the effectiveness of various OM practices, whether they are used in an aligned dominant organizational culture profile or in an eclectic organizational culture profile.Originality/valuePrevious research on organizational culture provides a limited understanding of the effectiveness of OM practices in the presence of strategic tensions, such as opposing organizational cultures or opposing targeted outcomes. This research concludes that the validity of the contingency or paradox perspective depends on strategic tensions faced, with important implications for research and practice.
Exploring the hierarchy of motivations in the wine purchase behavior of Chinese young wine consumers
Authors: Peng Dingkang , Huang Chia-Hsing 
Published: September 2024

Purpose
This paper aims to explore the hierarchy of motivations behind Chinese young wine consumers’ wine-purchasing behavior.

Design/methodology/approach
This study used a random and snowball sampling technique to collect data from Chinese young wine consumers. Ultimately, 840 participants were included, representing diverse geographic regions across China. The gathered data was analyzed to explore wine customer behavior using SPSS and AMOS.

Findings
The hierarchical structure of motivations guiding young consumers’ wine consumption becomes apparent when analyzed across ascending levels: from considerations of health benefits and emotional assessments to social interactions and status symbols. These factors wield significant influence over the purchase of wines among Chinese young wine consumers. Moreover, these consumption motivations notably impact consumption behavior by mediating through consumption intentions.

Originality/value
This study integrates the theory of planned behavior with Maslow’s hierarchy of needs, systematically identifying four primary motivations that hierarchically influence wine consumption among Chinese young wine consumers. It empirically validates the relationships between motivations, intentions and behaviors, underscoring intentions as a mediating factor linking motivations and behaviors.