bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans-complementation by the RecB nuclease domain of RecBCD enzyme reveals new insight into RecA loading upon χ recognition
Authors: Pavankumar Theetha L. , Jason Wong C. , Wong Yun Ka , Spies Maria , Kowalczykowski Stephen C. 
Published: May 2023

SummaryThe loading of RecA onto ssDNA by RecBCD is an essential step of RecBCD-mediated homologous recombination. RecBCD facilitates RecA-loading onto ssDNA in a χ-dependent manner via its RecB nuclease domain (RecBn). Before recognition of χ, RecBnis sequestered through interactions with RecBCD. It was proposed that upon χ-recognition, RecBnundocks, allowing RecBnto swing out via a contiguous 70 amino acid linker to reveal the RecA-loading surface, and then recruit and load RecA onto ssDNA. We tested this hypothesis by examining the interactions between RecBn(RecB928–1180) and truncated RecBCD (RecB1–927CD) lacking the nuclease domain. The reconstituted complex of RecB1–927CD and RecBnis functionalin vitroandin vivo. Our results indicate that despite being covalently severed from RecB1–927CD, RecBncan still load RecA onto ssDNA, establishing that RecBndoes not function at the end of its flexible linker. Instead, RecBCD undergoes a χ-induced intramolecular rearrangement to reveal a RecA-loading surface.
Cancer-associated fibroblast ADAM17 mediates a feed-forward loop promoting cancer cell migration
Authors: Perciato Maria L , Whawell Simon A , Lambert Daniel W 
Published: May 2023

AbstractOne of the ways in which cancer associated fibroblasts (CAF) influence the tumour-microenvironment (TME) is by releasing soluble factors to elicit responses in nearby cells. These factors may be released by modification of the extracellular matrix (ECM), secretion from intracellular compartments, or proteolytic cleavage from the cell surface. A major mediator of proteolytic processing of cell surface proteins is the ‘a disintegrin and metalloproteinase’ (ADAM) family, commonly ADAM17. The role of ADAM17 in CAF, however, remains largely unknown.Here, we show that expression of ADAM17 was induced in normal oral fibroblasts (NOF) and CAF by exposure to oral cancer cell-derived conditioned medium and depletion of ADAM17 reduced the ability of CAF to promote cancer cell migration by negatively regulating cancer cell-associated N-cadherin. Proteomic analysis of ADAM17-depleted CAF revealed changes in the expression of pro-tumorigenic proteins, including fibroblast growth factor 2 (FGF2). Inhibition of FGF2/FGFR1 signalling abrogated the pro-migratory effects of CAF by reducing cancer cell-associated N-cadherin, an effect rescued by addition of recombinant FGF2.Taken together, these results indicate a novel molecular mechanism underpinning cancer cell migration in which tumour-derived factors induce ADAM17 expression in CAF, thus initiating a feed-forward loop wherein CAF release FGF2 to stimulate N-cadherin-dependent cancer cell migration.
Flight heights of Scopoli’s shearwatersCalonectris diomedeain the context of offshore wind farm developments
Authors: Courbin Nicolas , Besnard Aurélien , Boncourt Etienne , Grémillet David 
Published: May 2023

AbstractSeabird face new risks through collisions with offshore wind turbines. Wind energy projects are emerging in the Mediterranean Sea, and unbiased knowledge on seabird flight altitudes are scarce in this area. Indeed, previous flight height observations were carried out from boats during daytime, and only in good weather conditions. We measured flight heights of 13 Scopoli’s shearwaters,Calonectris diomedea, one of the three endemic shearwater species in the Mediterranean, using highly precise barometric data loggers. The birds were equipped at the largest French colony of Scopoli’s shearwater in the Marseille archipelago. Birds from this location routinely visit forthcoming wind farm areas, within 50 km of their breeding site. We found that Scopoli’s shearwaters flew at very low altitudes with a mean flight height of 1.8 ± 2.7 m (± SD) above sea level. Birds therefore rarely (<0.02%) flew within the vertical envelop of collision risk with wind turbines. Ours results are coherent with field observations and the dynamic soaring flight technique used by shearwaters.Nevertheless, collision risk may increase following behavioural modifications close to wind turbines.
3D organoid modeling identified that targeting IGF1R signaling may overcome drug resistance in breast cancer
Authors: Mittal Ekansh , Qian David 
Published: May 2023

AbstractBreast cancer is the most frequently diagnosed cancer and the second largest cause of cancer deaths in women. However, drug resistance and poor response to treatments are common. Thus, there is an unmet need to identify new treatments and effective lab-based drug testing methods. Here we established a novel 3-dimensional organoid method by co-culturing cancer cells with healthy endothelial cells for longer-term testing of new drug combinations that combat drug resistance. As a proof-of-concept we showed that paclitaxel efficacy can be improved by combining it with AKT inhibitors. In addition, we identified a new triple combination of paclitaxel, HER2 inhibitor, and IGF1R inhibitor, which is more effective in increasing cell death and reducing organoid growth. Interestingly, many IGF1R pathway members are upregulated in breast cancer patients, and high expression is associated with poor survival, indicating that IGF1R is an attractive therapeutic target. Overall, using this novel organoid method, we can mimic more accurate culture conditions and identify new targets to be tested in clinical trials. Our approach is applicable to various cancers to improve patients’ outcomes.
Optimal reaching subject to computational and physical constraints reveals structure of the sensorimotor control system
Authors: Greene Patrick , Bastian Amy , Schieber Marc H. , Sarma Sridevi V. 
Published: May 2023

AbstractOptimal feedback control provides an abstract framework describing the architecture of the sensorimotor system without prescribing implementation details such as what coordinate system to use, how feedback is incorporated, or how to accommodate changing task complexity. We investigate how such details are determined by computational and physical constraints by creating a model of the upper limb sensorimotor system in which all connection weights between neurons, feedback, and muscles are unknown. By optimizing these parameters with respect to an objective function, we find that the model exhibits a preference for an intrinsic (joint angle) coordinate representation of inputs and feedback and learns to calculate a weighted feedforward and feedback error. We further show that complex reaches around obstacles can be achieved by augmenting our model with a path-planner based on via points. The path-planner revealed “avoidance” neurons that encode directions to reach around obstacles, and “placement” neurons that make fine-tuned adjustments to via point placement. Our results demonstrate the surprising capability of computationally constrained systems and highlight new characteristics of the sensorimotor system.
Accessibility and activity of transcriptional regulatory elements during sea urchin embryogenesis and differentiation
Authors: Arenas-Mena Cesar , Akin Serhat 
Published: May 2023

AbstractTranscriptional regulatory elements (TREs) are the primary nodes of the gene regulatory networks that control development. TREs are identified by PRO-seq and their accessibility by ATAC-seq during sea urchin embryonic development and differentiation. Our analysis identifies surprisingly early accessibility in 4-cell cleavage embryo TREs that is not necessarily followed by subsequent transcription, and an excess of ATAC-seq peaks transcriptionally disengaged during the stages analyzed. Embryonic accessibility shifts are driven by transcriptionally engaged TREs, and PRO-seq transcriptional differences at TREs provide more contrast among embryonic stages than ATAC-seq accessibility differences. TRE accessibility reaches a maximum around the 20-hour late blastula, which coincides with major embryo regionalizations. At the same time, a large number of distal TREs become transcriptionally disengaged, in support of an early Pol II primed model for developmental gene regulation that eventually resolves in transcriptional activation or silencing. A transcriptional potency model based on labile nucleosome TRE occupancy driven by DNA sequences and the prevalence of histone variants is proposed in order to explain the basal accessibility of transcriptionally inactive TREs during early embryogenesis.Summary statementGenomic profiles deciphering the location and activity of regulatory elements that control gene expression suggest general mechanisms of regulatory potency in early sea urchin embryos.
In vivo screening of tumor-hepatocyte interactions identifies Plexin B2 as a gatekeeper of liver metastasis
Authors: Borrelli Costanza , Roberts Morgan , Eletto Davide , Lafzi Atefeh , Kretz Jonas A. , Fazilaty Hassan , Hussherr Marie-Didiée , Guido Vinzoni Elena , Handler Kristina , Michler Jan , Adivarahan Srivathsan , Piscuoglio Salvatore , Ficht Xenia , Moor Andreas E. 
Published: May 2023

AbstractIt is estimated that only 0.02% of disseminated tumor cells are able to seed overt metastases1. While this indicates the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unknown. Combining transposon technology2and fluorescent niche labeling3, we developed anin vivoCRISPR activation screen to systematically investigate the influence of hepatocytes on metastatic seeding in the liver. Our approach enabled the identification of Plexin B2 as a critical host-derived regulator of metastasis. Plexin B2 upregulation in hepatocytes dramatically enhances grafting in colorectal and pancreatic cancer syngeneic models, and promotes seeding and survival of patient-derived organoids. Notably, ablation of Plexin B2 in hepatocytes prevents mesenchymal-to-epithelial transition of extravasated tumor cells and thereby almost entirely suppresses liver metastasis. We dissect a mechanism by which Plexin B2 interacts with class 4 semaphorins on tumor cells, activating Rac1 signaling and actin cytoskeleton remodeling, thereby promoting the acquisition of epithelial traits. Our findings highlight the essential role of signals from the liver parenchyma for the survival of disseminated tumor cells, prior to the establishment of a growth promoting niche. They further suggest that acquisition of epithelial traits is required for the adaptation of extravasated cells to their new tissue environment. Targeting of Plexin B2 on hepatocytes shields the liver from colonizing cells and thus presents an innovative therapeutic strategy for preventing metastasis. Finally, our screening technology, which evaluates host-derived extrinsic signals rather than tumor-intrinsic factors for their ability to promote metastatic seeding, is broadly applicable and lays a framework for the screening of environmental constraints on metastasis in other organs and cancer types.
Autism and social media: a systematic review of the user experience
Authors: Hudson Nicholas Andrew , Linnane Jake M. , Rayner-Smith Kelly 
Published: May 2023

Purpose
Social media use in autistic people has been identified as a potential avenue for less pressured social contact. Given shifts towards online socialisation, this study aims to systematically review the available literature on how autistic people experience and use social media.

Design/methodology/approach
A systematic review was carried out using the preferred reporting items for systematic reviews and meta-analyses system, with relevant literature reviewed and synthesised using a narrative approach. Inclusion criteria included adults and/or adolescents as the sole sample, a focus on autism and social media use as the sole/main topic.

Findings
A total of 1,278 research studies were initially identified; following screening, 15 papers were reviewed. Studies demonstrated some support for the positive role social media can play and presented its use as a smart adaptation for the challenges of neurotypical socialising. For autistic people, social media may provide a balance between meeting the need to be connected to people without the pressure of managing aspects, such as tone of voice or body language.

Research limitations/implications
Most studies were questionnaire-based with substantial threats to validity. Samples were self-selecting, with autism status not always confirmed. Individual studies used a broad approach to the definition of social media, including online gaming and other online activities, precluding firm conclusions being made.

Practical implications
There may be a Goldilocks “just right” level of social media contact that could maximise connectedness to others without impacting negatively on mental health, offline relationships and activities of daily living.

Originality/value
This paper presents a novel account of research from case studies and larger scale questionnaire studies.
Corporate governance in the COVID-19 pandemic: current practices and potential improvement
Authors: Alshhadat Mohammad Q. , Al-Hajaya Krayyem 
Published: May 2023

Purpose
The purpose of this paper is to analyse the effect of the COVID-19 pandemic on corporate governance and internal control in general. In addition, this paper attempts to develop a new corporate governance model that flexibly addresses conditions like those brought into the business environment by COVID-19.

Design/methodology/approach
Thirteen semi-structured interviews were conducted with chairpersons, CEOs and directors from companies listed on the FTSE 350.

Findings
This study suggests a corporate governance model, which we call Eunomia, which we believe will help businesses to navigate the unusual conditions resulting from COVID-19 and similar types of crises that lead to major disruption for businesses and society. The model includes five pillars that support governance, namely, flexibility, IT infrastructure, risk management, internal control and policies and procedures.

Practical implications
Implications for practice and policymakers. Based on the research outcomes, the authors suggest that the board of directors establishes policies that ensure supply diversity and that businesses do not rely on a single or limited number of suppliers, thereby making themselves vulnerable to supply chain disruption with those suppliers.

Originality/value
This paper presents an original contribution to the accounting literature relating to corporate governance and internal control systems, specifically in terms of how businesses can optimally operate under uncontrollable conditions resulting from pandemics, and similar situations.
The desire for employability and self-exploitation: concretizing Lacan's psychoanalysis on employability
Authors: Shah Muzammel 
Published: May 2023

PurposeAlthough commitment and employability are legitimized in the current world of work, they also have a dark side that has been ignored in the extant literature. To tackle this gap, the study developed and examined a comprehensive theoretical framework including learning, motivation, commitment, employability and self-exploitation. Limited research exists that explicitly examines this relationship or explores its potential implications. The author theorizes employability as a cultural fantasy that ends up in self-exploitation.Design/methodology/approachThe study concretizes Lacan's (1977; 1981 and 1988) psychoanalysis, utilizing a sample of 658 subjects from eight industries. The hypothesized relationships were examined using structural equation modeling (SEM) in AMOS.FindingsThe findings provided support for the hypothesized relationships. Employability escorts to self-exploitation. Those employees who try to remain relevant to their firms continue to engage in employability activities end up being exploited in this process.Research limitations/implicationsThe study provides a new roadmap to scholars of employability who wish to explore the domain further.Practical implicationsThe theoretical knowledge from this research will inform practice. It will influence managers and policymakers in the organization as well as politicians. Although the macroaspects of the organizational environment are beyond the control of an organization, the development efforts of the organization should be real and should not estrange individuals from their true nature. The real intent should be to unite the individual with its true nature. This way, it will be real development and will empower individuals rather than exploitation.Social implicationsThe finding that commitment is linked to self-exploitation via employability has implications for managers and policymakers. To avoid estrangement and exploitation, the organization should focus on employee real development. To have an ideal workplace, where employees unite with their nature, the organization should invest in employees, focus on their real needs, emphasize their career prospects and constantly provide them with learning and growth opportunities. In addition to material compensation, the organization should connect people with their true spirit. An organization that is concerned with people's real needs and real development will have a pool of human capital that will create real value for the organization and society as well.Originality/valueThe dark side of employability has been ignored in the extant literature. Limited research exists that explicitly examines this relationship or explores its potential implications. This study is an initiative for such debate.
LGBTQ+ in workplace: a systematic review and reconsideration
Authors: Maji Sucharita , Yadav Nidhi , Gupta Pranjal 
Published: May 2023

PurposeThe inclusion of LGBTQ + persons (lesbian, gay, bisexual, transgender, queer and having other sexual orientations and gender identities) is a crucial step in improving gender diversity in the workplace; however, till date, it remains a significant challenge for human resource management professionals. The current study critically examines this issue of an inclusive workplace for LGBTQ + people through a systematic review of the existing research that has empirically studied their experiences at the workplace. It also examines the resistance and challenges organizations face in LGBTQ + diversity training and provides future research avenues.Design/methodology/approachFor systematically reviewing the literature, Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) model has been used. A total of 101 empirical studies have been reviewed.FindingsThe result shows that LGBTQ + people encounter multiple negative workplace experiences, including proximal (hiring discrimination and housing discrimination) and distal workplace discrimination (unsafe work climate, microaggressions and harassment). These aversive experiences lead to work stress while also mandating that people manage their sexual identity and style of dressing. This stress, in turn, impacts their work–family outcomes, job satisfaction and decision-making with regard to their careers.Originality/valueThe paper provides a holistic understanding of the aversive workplace experiences encountered by sexual minorities.
Thriving in management innovation: an institutional perspective
Authors: Khosravi Pouria , Newton Cameron , Rezvani Azadeh , Ghanbarzadeh Reza , Akbari Morteza 
Published: May 2023

PurposeManagement innovation is one of the most vital practices underpinning economic growth and is considered to be one of the fundamental components of gaining a superior business position in market conditions that are continually fluctuating. Drawing upon neo-institutional theory as well as absorptive capacity, the current empirical study unpacks the relationships between external institutional forces (i.e. regulative, mimetic and normative pressures) and management innovation through investigating the role of absorptive capacity as a mediator.Design/methodology/approachThe research model is tested using survey data from Australian organisations. The study used Partial Least Squares (PLS), a component-based structural equation modelling (SEM) method, in order to perform the data analysis.FindingsThe results confirm that the various dimensions of institutional forces have diverse influences on management innovation. The authors found mimetic and normative pressures have positive influences on realised and potential absorptive capacity of an organisation. In addition, realised absorptive capacity mediates the relations between institutional forces and management innovation.Originality/valueDissimilar to preceding studies, this research shows that organisations not only innovate to pursue higher performance but sometimes strive for legitimacy. In addition, the significant associations between absorptive capacity and management innovation and the mediation role clearly signify that institutional forces and absorptive capacity play significant roles in the adoption of management innovation.
The role of bricolage in countering resource constraints and uncertainty in start-up business model innovation
Authors: Xu Sha , He Jie , Morrison Alastair M. , Su Xiaohua , Zhu Renhong 
Published: May 2023

PurposeDrawing from resource orchestration theory, this research proposed an integrative model that leverages insights into counter resource constraints and uncertainty in start-up business model innovation (BMI). It investigated the influences of entrepreneurial networks and effectuation on BMI through bricolage in uncertain environments.Design/methodology/approachThe research surveyed 481 start-ups in China. LISREL 8.80 and SPSS 22.0 were employed to test the validity and reliability of key variables, respectively. Additionally, hypotheses were examined through multiple linear regression.FindingsFirst, entrepreneurial networks and effectuation were positively related to BMI, and combining these two factors improved BMI for start-ups. Second, bricolage contributed to BMI and played mediating roles in translating entrepreneurial networks and effectuation into BMI. Third, environmental uncertainty weakened the linkage between bricolage and BMI.Research limitations/implicationsFuture research should replicate the results in other countries because only start-ups in China were investigated in the study, and it is necessary to extend this research by gathering longitudinal data. This research emphasized the mediating effects of bricolage and the moderating influence of environmental uncertainty, and new potential mediating and moderating factors should be explored between resources and BMI.Originality/valueThere are three significant theoretical contributions. First, the findings enrich the literature on the complex antecedents of BMI by combining the impacts of entrepreneurial networks and effectuation. Second, an overarching framework is proposed explaining how bricolage (resource management) links entrepreneurial networks and effectuation and BMI. Third, it demonstrates the significance of environmental uncertainty in the bricolage–BMI linkage, deepening the understanding of the bricolage boundary condition.