bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive genetic catalog of human double-strand break repair
Authors: López de Alba Ernesto , Salguero Israel , Giménez-Llorente Daniel , Fernández-Sanromán Ángel , Casajús-Pelegay Ester , Terrón-Bautista José , Barroso-González Jonathan , Bernal Juan A. , Macintyre Geoff , Fernández-Leiro Rafael , Losada Ana , Cortés-Ledesma Felipe 
Published: August 2024

AbstractThe analysis of DNA sequence outcomes provides molecular insights into double-strand break (DSB) repair mechanisms. By employing parallel in-pool profiling of Cas9-induced indels within a genome-wide knockout library, we present a comprehensive catalog detailing how virtually every human gene influences the DSB repair process. This REPAIRome resource is validated through the identification of novel mechanisms, pathways and factors involved in DSB repair, including unexpected opposing roles for XLF and PAXX in DNA end processing, a molecular explanation for Cas9-induced multi-nucleotide insertions, the identification of HLTF as a DSB-repair factor, the involvement of the SAGA complex in microhomology-mediated end joining, and importantly, an indel mutational signature linked to VHL loss, renal carcinoma and hypoxia. Collectively, these results exemplify the potential of REPAIRome to drive future discoveries in DSB repair, CRISPR-Cas gene editing and the etiology of cancer mutational signatures.
Synapsin condensation is governed by sequence-encoded molecular grammars
Authors: Hoffmann Christian , Ruff Kiersten M. , Edu Irina A. , Shinn Min Kyung , Tromm Johannes V. , King Matthew R. , Pant Avnika , Ausserwöger Hannes , Morgan Jennifer R. , Knowles Tuomas P. J. , Pappu Rohit V. , Milovanovic Dragomir 
Published: August 2024

AbstractMultiple biomolecular condensates coexist at the pre- and post-synapse to enable vesicle dynamics and controlled neurotransmitter release in the brain. In pre-synapses, intrinsically disordered regions (IDRs) of synaptic proteins are drivers of condensation that enable clustering of synaptic vesicles (SVs). Using computational analysis, we show that the IDRs of SV proteins feature evolutionarily conserved non-random compositional biases and sequence patterns. Synapsin-1 is essential for condensation of SVs, and its C-terminal IDR has been shown to be a key driver of condensation. Focusing on this IDR, we dissected the contributions of two conserved features namely the segregation of polar and proline residues along the linear sequence, and the compositional preference for arginine over lysine. Scrambling the blocks of polar and proline residues weakens the driving forces for forming micron-scale condensates. However, the extent of clustering in subsaturated solutions remains equivalent to that of the wild-type synapsin-1. In contrast, substituting arginine with lysine significantly weakens both the driving forces for condensation and the extent of clustering in subsaturated solutions. Co-expression of the scrambled variant of synapsin-1 with synaptophysin results in a gain-of-function phenotype in cells, whereas arginine to lysine substitutions eliminate condensation. We report an emergent consequence of synapsin-1 condensation, which is the generation of interphase pH gradients realized via differential partitioning of protons between coexisting phases. This pH gradient is likely to be directly relevant for vesicular ATPase functions and the loading of neurotransmitters. Our study highlights how conserved IDR grammars serve as drivers of synapsin-1 condensation.Research HighlightsDistinct biomolecular condensates formed by pre-synaptic proteins contain a unique bias of sequence grammars within their IDRs.The IDR of synapsin-1, the essential protein for the clustering of synaptic vesicles, has a conserved compositional bias for Arg and blockiness of proline/polar residues.Using sequence designs, we uncovered how conserved sequence features of the driver IDR of synapsin-1 affect condensation in vitro and in cells.Synapsin-1 condensates are defined by a measurable interphase pH gradient.
Differential Dynamics and Roles of FKBP51 Isoforms and Their Implications for Targeted Therapies
Authors: Martinelli Silvia , Hafner Kathrin , Koedel Maik , Knauer-Arloth Janine , Gassen Nils C , Binder Elisabeth B 
Published: August 2024

AbstractThe expression of FKBP5, and its resulting protein FKBP51, is strongly induced by stress and glucocorticoids. Numerous studies have explored their involvement in a plethora of cellular processes and diseases, including psychiatric disorders, inflammatory conditions and cancer. However, there is a lack of knowledge on the role of the different RNA splicing variants and the two protein isoforms that originate from the human FKBP5 locus, especially in response to glucocorticoids. In this study we usein vitromodels as well as peripheral blood cells of a human cohort to show that the two expressed variants are both dynamically upregulated following dexamethasone. We also investigate the subcellular localization of the protein isoforms, their degradation dynamics as well as their differential role in known cellular pathways. The results shed light on the difference of the two variants and highlight the importance of differential analyses in future studies with implications for targeted drug design.
Polo-like kinase 1 prevents excess microtubule polymerization inC. elegansoocytes to ensure faithful meiosis
Authors: Narula Juhi G. , Wignall Sarah M. 
Published: August 2024

ABSTRACTSexual reproduction relies on meiosis, a specialized cell division program that produces haploid gametes. Oocytes of most organisms lack centrosomes, and therefore chromosome segregation is mediated by acentrosomal spindles. Here, we explore the role of Polo-like kinase 1 (PLK-1) inC. elegansoocytes, revealing mechanisms that ensure the fidelity of this unique form of cell division. Previously, PLK-1 was shown to be required for nuclear envelope breakdown and chromosome segregation in oocytes. We now find that PLK-1 is also required for establishing and maintaining acentrosomal spindle organization and for preventing excess microtubule polymerization in these cells. Additionally, our studies revealed an unexpected new role for this essential kinase. While PLK-1 is known to be required for centrosome maturation during mitosis, we found that removal of this kinase from oocytes caused premature recruitment of pericentriolar material to the sperm-provided centrioles following fertilization. Thus, PLK-1 suppresses centrosome maturation during oocyte meiosis, which is opposite to its role in mitosis. Taken together, our work reveals multiple new roles for PLK-1 in oocytes, identifying PLK-1 as a key player that promotes faithful acentrosomal meiosis.
A targeted CRISPR screen identifies ETS1 as a regulator of HIV latency
Authors: Ashokkumar Manickam , Hafer Terry L , Felton Abby , Archin Nancie M. , Margolis David M , Emerman Michael , Browne Edward P 
Published: August 2024

AbstractHuman Immunodeficiency virus (HIV) infection is regulated by a wide array of host cell factors that combine to influence viral transcription and latency. To understand the complex relationship between the host cell and HIV latency, we performed a lentiviral CRISPR screen that targeted a set of host cell genes whose expression or activity correlates with HIV expression. We further investigated one of the identified factors - the transcription factor ETS1 and found that it is required for maintenance of HIV latency in a primary CD4 T cell model. Interestingly, ETS1 played divergent roles in actively infected and latently infected CD4 T cells, with knockout of ETS1 leading to reduced HIV expression in actively infected cells, but increased HIV expression in latently infected cells, indicating that ETS1 can play both a positive and negative role in HIV expression. CRISPR/Cas9 knockout of ETS1 in CD4 T cells from ART-suppressed people with HIV (PWH) confirmed that ETS1 maintains transcriptional repression of the clinical HIV reservoir. Transcriptomic profiling of ETS1-depleted cells from PWH identified a set of host cell pathways involved in viral transcription that are controlled by ETS1 in resting CD4 T cells. In particular, we observed that ETS1 knockout increased expression of the long non-coding RNA MALAT1 that has been previously identified as a positive regulator of HIV expression. Furthermore, the impact of ETS1 depletion on HIV expression in latently infected cells was partially dependent on MALAT1. Overall, these data demonstrate that ETS1 is an important regulator of HIV latency and influences expression of several cellular genes, including MALAT1, that could have a direct or indirect impact on HIV expression.Author SummaryHIV latency is a major obstacle for the eradication of HIV. However, molecular mechanisms that restrict proviral expression during therapy are not well understood. Identification of host cell factors that silence HIV would create opportunities for targeting these factors to reverse latency and eliminate infected cells. Our study aimed to explore mechanisms of latency in infected cells by employing a lentiviral CRISPR screen and CRISPR/Cas9 knockout in primary CD4 T cells. These experiments revealed that ETS1 is essential for maintaining HIV latency in primary CD4 T cells and we further confirmed ETS1’s role in maintaining HIV latency through CRISPR/Cas9 knockout in CD4 T cells from antiretroviral therapy (ART)-suppressed individuals with HIV. Transcriptomic profiling of ETS1-depleted cells from these individuals identified several host cell pathways involved in viral transcription regulated by ETS1, including the long non-coding RNA MALAT1. Overall, our study demonstrates that ETS1 is a critical regulator of HIV latency, affecting the expression of several cellular genes that directly or indirectly influence HIV expression.
Humans can use positive and negative spectrotemporal correlations to detect rising and falling pitch
Authors: Vaziri Parisa A. , McDougle Samuel D. , Clark Damon A. 
Published: August 2024

AbstractTo discern speech or appreciate music, the human auditory system detects how pitch increases or decreases over time. However, the algorithms used to detect changes in pitch, or pitch motion, are incompletely understood. Here, using psychophysics, computational modeling, functional neuroimaging, and analysis of recorded speech, we ask if humans can detect pitch motion using computations analogous to those used by the visual system. We adapted stimuli from studies of vision to create novel auditory correlated noise stimuli that elicited robust pitch motion percepts. Crucially, these stimuli are inharmonic and possess no persistent features across frequency or time, but do possess positive or negative local spectrotemporal correlations in intensity. In psychophysical experiments, we found clear evidence that humans can judge pitch direction based only on positive or negative spectrotemporal intensity correlations. The key behavioral result—robust sensitivity to the negative spectrotemporal correlations—is a direct analogue of illusory “reverse-phi” motion in vision, and thus constitutes a new auditory illusion. Our behavioral results and computational modeling led us to hypothesize that human auditory processing may employ pitch direction opponency. fMRI measurements in auditory cortex supported this hypothesis. To link our psychophysical findings to real-world pitch perception, we analyzed recordings of English and Mandarin speech and found that pitch direction was robustly signaled by both positive and negative spectrotemporal correlations, suggesting that sensitivity to both types of correlations confers ecological benefits. Overall, this work reveals how motion detection algorithms sensitive to local correlations are deployed by the central nervous system across disparate modalities (vision and audition) and dimensions (space and frequency).
CRISPR-Cas13d as a molecular tool to achieve targeted gene expression knockdown in chick embryos
Authors: Kim Minyoung , Hutchins Erica J. 
Published: August 2024

ABSTRACTThe chick embryo is a classical model system commonly used in developmental biology due to its amenability to gene perturbation experiments. Pairing this powerful model organism with cutting-edge technology can significantly expand the range of experiments that can be performed. Recently, the CRISPR-Cas13d system has been successfully adapted for use in zebrafish, medaka, killifish, and mouse embryos to achieve targeted gene expression knockdown. Despite its success in other animal models, no prior study has explored the potential of CRISPR-Cas13d in the chick. Here, we present an adaptation of the CRISPR-Cas13d system to achieve targeted gene expression knockdown in the chick embryo. As proof-of-principle, we demonstrate the knockdown of PAX7, an early neural crest marker. Application of this adapted CRISPR-Cas13d technique resulted in effective knockdown of PAX7 expression and function, comparable to knockdown achieved by translation-blocking morpholino. CRISPR-Cas13d complements preexisting knockdown tools such as CRISPR-Cas9 and morpholinos, thereby expanding the experimental potential and versatility of the chick model system.
A versatile dual reporter to identify ribosome pausing motifs alleviated by translation elongation factor P
Authors: Tomasiunaite Urte , Brewer Tess , Burdack Korinna , Brameyer Sophie , Jung Kirsten 
Published: August 2024

AbstractProtein synthesis is influenced by the chemical and structural properties of the amino acids incorporated into the polypeptide chain. Motifs with consecutive prolines can slow down translation speed and cause ribosome stalling. Translation elongation factor P (EF-P) facilitates peptide bond formation in these motifs, thereby alleviating stalled ribosomes and restoring regular translational speed. Ribosome pausing at various polyproline motifs has been intensively studied using a range of sophisticated techniques, including ribosome profiling, proteomics, andin vivoscreenings with reporters incorporated into the chromosome. However, the full spectrum of motifs which cause translational pausing inEscherichia colihas not yet been identified. Here we describe a plasmid-based dual reporter for rapid assessment of pausing motifs. This reporter contains two coupled genes encoding mScarlet-I and chloramphenicol acetyltransferase to screen motif libraries based on both bacterial fluorescence and survival. In combination with a diprolyl motif library, we use this reporter to reveal motifs of different pausing strengths in anE. colistrain lackingefp.Subsequently, we use the reporter for a high-throughput screen of four motif libraries, with and without prolines at different positions, sorted by fluorescence-associated cell sorting (FACS) and identify new motifs that influence translational efficiency of the fluorophore. Our study provides anin vivoplatform for rapid screening of amino acid motifs that affect translational efficiencies.
Implementation of sustainability activities in food retail chains
Authors: Boskova Iveta , Valenta Matěj , Dolanova Ivana 
Published: August 2024

PurposeThis study aims to examine the implementation of sustainability activities in food retail chains operating in the Czech market and discusses the specific activities that influence their implementation.Design/methodology/approachUsing the neo-institutional theory as a framework, the research employs qualitative content analysis with an explanatory and inductive approach based on the stratification of data collected by multiple-round, personal, face-to-face interviews by the researchers with managers of the Czech headquarters of multinational food retail chains.FindingsThere is lively development in activities in the fields of the environment and social welfare, while the activities in governance and economic resilience are more stabilised. To remain ahead of the competition, retail chains aim to implement and communicate as many activities as possible where at least some links to sustainability can be found. A lack of benchmarks and clear definitions reduce the ability to determine their degree of engagement. Thus, market actors are inundated with sustainability claims leading to inflation of the concept, while significant achievements are drowned.Originality/valueThis paper, based on empirical research, contributes to the current literature by showing inflation of the sustainability concept as one of the key effects of retail-chain competition. In this context, it also strengthens previous findings on the profitability motive behind sustainability activities. Moreover, we have developed our own stratification method, enabling differentiation between activities getting the most attention due to their progressive phase and those where development is in the background.
Construction 4.0 technology and lean construction ambidexterity capability in China’s construction industry: a sociotechnical systems perspective
Authors: Fang Yanqing , Gao Shang 
Published: August 2024

Purpose
This study aims to explore the level of adoption of Construction 4.0 (C4.0) technologies and of Lean Construction (LC) ambidexterity capability in China’s construction industry. By incorporating C4.0 and LC ambidexterity into a sociotechnical systems (STS) framework, this research provides practical insights for construction practitioners and companies seeking C4.0 and LC.

Design/methodology/approach
The study adopts the questionnaire survey method. Data was obtained from Chinese construction professionals working on projects using C4.0 technologies. The data were analysed using mean score ranking and three nonparametric techniques, including the Wilcoxon signed-rank test and the Spearman rank correlation.

Findings
According to the ranking analysis, building information modelling and offsite construction have the highest adoption level, while additive manufacturing and blockchain rank lowest. Digital technology is more widely used in China’s construction industry than in physical technology. Many C4.0 technologies are significantly correlated with LC ambidexterity. Based on the STS perspective, we propose a holistic approach that incorporates C4.0 technologies and LC ambidexterity.

Originality/value
Conceptually, the study incorporates C4.0 and LC ambidexterity into the STS framework. Empirically, this study fills the gap in the current literature by exploring the level of C4.0 technology adoption in the Chinese construction industry, as well as the level of LC ambidexterity capabilities. Construction companies can use this framework to make strategic decisions regarding investments in LC practices and the adoption of C4.0 technologies, such as investing in staff skill training and new technology deployment to adapt to the ever-changing environment.
Navigating the integration of ChatGPT in UAE’s government sector: challenges and opportunities
Authors: Goher Ghada Nabil 
Published: August 2024

PurposeThis research examines how responsible deployment of ChatGPT in the UAE’s government sector, guided by New Public Management principles, can enhance customer journeys by integrating services across government bodies. Through semi-structured interviews with UAE government officers, the study investigates this approach’s benefits, challenges, and applications for achieving efficient and integrated public service delivery.Design/methodology/approachThis research adopts a qualitative approach, purposive sampling strategy, and semi-structured interviews to explore the subjective viewpoints of 20 high-level UAE government authorities. The thematic analysis uncovers ChatGPT’s benefits, challenges, and applications, aligning with New Public Management principles.FindingsThematic analysis reveals four themes: Benefits and Applications of ChatGPT, Challenges, Strategies to Overcome Challenges, and Steps for Customer Journey Enhancement through ChatGPT.Research limitations/implicationsThe analysis is based on participant responses provided during the interviews, which may be subject to biases or incomplete information. Secondly, the study focuses solely on the provided applications and participant responses, limiting the generalizability of the conclusions to other contexts.Practical implicationsThe implementation of ChatGPT in the government sector has practical implications for transforming its operations and enhancing communication, efficiency, decision-making, and service offerings: citizen engagement, streamlined processes, and informed governance.Originality/valueThis study uniquely examines ChatGPT’s role in government, offering insights into communication, efficiency, decision-making, and service offerings. Identifying hurdles enriches understanding of ChatGPT’s practical integration in government.
Exploring the competitiveness of Indian technological start-ups – the case study approach
Authors: Wasi Khushnuma , Pantawane Tisha Rajeev , Parameswar Nakul , Ganesh M.P. 
Published: August 2024

Purpose
Technological start-ups are significant contributor to the innovation and employment provider in an economy. Numerous technological start-ups are established every year; however, only a miniscule percentage of these technological start-ups sustain and scale up in the long run. The aim of this study is to investigate the factors that affect Indian technological start-ups’ competitiveness.

Design/methodology/approach
Case study analysis of two technological start-ups (namely, WayCool and Moglix) is undertaken to study the factors affecting the competitiveness of technological start-ups in India. Being a relatively underexplored theme of study in entrepreneurship and strategy, case analysis facilitates exploration and validation of factors influencing competitiveness. Information for case study analysis is drawn from secondary sources of information. The collected data undergoes deductive thematic analysis to systematically identify and examine recurring themes and patterns relevant to the competitiveness of Indian technological start-ups.

Findings
Case analysis reveals that innovation intensity, organisational agility and internationalisation influence competitiveness of technological start-ups. The importance of the role of each of these factors for entrepreneurial ventures has been highlighted in literature; however, their effect on competitiveness has not been examined in extant literature.

Research limitations/implications
Being among the few studies on the competitiveness of technological start-ups in specific and start-ups in general, this study highlights the gap in the literature and suggests the need for examining the competitiveness of technological start-ups.

Practical implications
For the practitioners, this study reinforces the need for entrepreneurs to emphasise fundamental factors that build competitiveness. Subsequently, the sources of competitiveness shall enable the start-up to gain a competitive advantage.

Originality/value
This is among the few studies to have explored the competitiveness of technological start-ups in the Indian context.