bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-evolution between PRDM9 and target sites and the Recombination Hotspot Paradox
Authors: Úbeda Francisco , Fyon Frederic , Bürger Reinhard 
Published: September 2022

AbstractRecombination often concentrates in small regions called recombination hotspots where recombination is much higher than the genome’s average. In many vertebrates, including humans, gene PRDM9 specifies which DNA motifs will be the target for breaks that initiate recombination ultimately determining the location of recombination hotspots. Because the sequence that breaks (allowing recombination) is converted into the sequence that does not break (preventing recombination), the latter sequence is over-transmitted to future generations and recombination hotspots are self-destructive. Given their self-destructive nature, recombination hotspots should eventually become extinct in genomes they are observed. While empirical evidence shows that individual hotspots do become inactive over time (die), hotspots are abundant in many vertebrates: a contradiction called the Recombination Hotspot Paradox. What saves recombination hotspots from their foretold extinction? Here we formulate a co-evolutionary model of the interaction among sequence specific gene conversion, fertility selection and recurrent mutation. We find that when fertility selection is weaker than gene conversion, fertility selection cannot stop individual hotspots from dying but can save them from extinction by driving their re-activation (resuscitation). It can also save them from extinction by driving the birth of new hotspots in target sites with small allelic variation. The amount of allelic variation that can result in the birth of a hotspot depends on the strength of fertility selection and the mutation rate. In our model mutations balance death and resuscitation of hotspots maintaining their numbers over time. Interestingly we find that mutations are responsible for the oscillation of individual hotspots being asynchronous across the genome such that the average recombination across the genome remains constant. Our model thus contributes to better understanding how new hotspots may be formed thus explaining the Recombination Hotspots Paradox. From a more applied perspective our work provides testable predictions regarding the relation between mutation and fertility with life expectancy of hotspots.
Modulation of the functional interfaces between retroviral intasomes and the human nucleosome
Authors: Mauro E. , Lapaillerie D. , Tumiotto C. , Charlier C. , Martins F. , Sousa S. F. , Métifiot M. , Weigel P , Yamatsugu K. , Kanai M. , Munier-Lehmann H. , Richetta C. , Batisse J. , Ruff M. , Delelis O. , Lesbats P. , Parissi V. 
Published: September 2022

ABSTRACTRetroviral integration into cell chromatin requires the formation of integrase-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes. To further study this mechanism we developed an alphaLISA approach using the prototype foamy virus (PFV) intasome and human nucleosome. This system allowed us to monitor the association between both partners and investigate the protein/protein and protein/DNA interactions engaged in the association with chromatin. Using this approach, we next screened the chemical OncoSET library and selected small molecules that could modulate the intasome/nucleosome complex. Molecules were selected as acting either on the DNA topology within the nucleosome or on the integrase/histone tail interactions. Within these compounds, doxorubicin and histone binders calixarenes were characterized using biochemical, structural and cellular approaches. These drugs were shown to inhibit PFV and HIV-1 integration in vitro as well as HIV-1 infection in primary PBMCs cells. Our work provides new information about intasome-nucleosome interaction determinants and paves the way for further unedited antiviral strategies that target the final step of intasome/chromatin anchoring.
Aberrant DNA repair is a vulnerability in histone H3.3-mutant brain tumors
Authors: Rondinelli Beatrice , Giacomini Giulia , Piquet Sandra , Chevallier Odile , Dabin Juliette , Bai Siau-Kun , Kim Byungjin , Siddaway Robert , Raught Brian , Coyaud Etienne , Shan Chun-Min , Reid Robert J.D. , Toda Takenori , Rothstein Rodney , Wilhelm Therese , Barra Viviana , Crane Alexander , Dubois Frank , Bandopadhayay Pratiti , Beroukhim Rameen , Naim Valeria , Jia Songtao , Hawkins Cynthia , Polo Sophie E. 
Published: September 2022

SummaryPediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent oncogenic mechanism, which fosters genome instability and tumor cell growth in H3.3 mutant pHGG, thus opening new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme Polynucleotide Kinase 3’-Phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.
Poor attentional control as a sex-specific biomarker to assess vulnerability to nicotine addiction in mice
Authors: Medrano Maria-Carmen , Darlot Florence , Cador Martine , Caillé Stephanie 
Published: September 2022

AbstractEvery day thousands of people smoke a first cigarette, exposing themselves to the risk of becoming addicts. But this risk is not equal from individual to individual, inviting the hypothesis of potential biomarkers for predicting baseline vulnerability to addiction. One property of nicotine is to increase attentional capacities. However, the role of this pro-cognitive nicotinic effect in initiation of habitual smoking is unknown. Here, we investigated whether the differential effects of nicotine on cognitive performance in mice were predictive of sensitivity to nicotine reward and, if so, whether this characteristic was sex dependent. Naïve populations of male and female mice were first assessed for their attentional performances in the attentional cued-Fixed-Consecutive-Number task (FCNcue) in baseline conditions and after nicotine injections (0.15 and 0.30 mg/kg). Next, all mice underwent nicotine-induced conditioned place preference (CPP) in order to evaluate inter-individual differences in nicotine (0.30 mg/kg) reward sensitivity. Our results showed that innately impulsive males, but not females, benefited from the pro-cognitive effect of nicotine and were also subsequently more sensitive to nicotine reward, indicating increased vulnerability to developing nicotine addiction. Females displayed a completely different behavioural pattern, whereby nicotine reward sensitivity was independent of baseline attentional performances. These results suggest that the pro-cognitive effect of nicotine plays a key role in the development of nicotine addiction in males but not females. Moreover, they signal that the cognitive processes and neurobiology underpinning innate impulsivity may differ significantly between males and females.
Comparing Cigarette-Cue Attentional Bias Between People With HIV/AIDS and People With Opioid Use Disorder Who Smoke
Authors: Rakesh Gopalkumar , Alcorn Joseph L , Khanal Rebika , Himelhoch Seth S , Rush Craig R 
Published: September 2022

AbstractBackgroundSpecial populations like people living with HIV/AIDS (PLWHA) and people with opioid use disorder (OUD) smoke tobacco cigarettes at rates three to four times greater than the general population. Patients with tobacco use disorder exhibit attentional bias (AB) for cigarette cues, which is theorized to be caused by classical conditioning and motivational salience. Eye tracking can quantify this bias by measuring fixation time (FT) on cigarette and matched neutral cues, which consequently helps calculate an AB score. Although previous studies have measured this bias in people who smoke without any other comorbid conditions, no study has measured this bias in special populations.MethodsWe analyzed eye tracking data collected from participants in two randomized clinical trials (RCTs). The study protocols that recruited participants were approved by Medical Institutional Review Board (IRB) at University of Kentucky and were registered on clinical trials.gov (NCT05049460, NCT05295953). We compared FT and AB score towards cigarette cues between PLWHA and people with OUD who smoke, using a visual probe task and Tobii Pro Fusion eye tracker. We used two cigarette cue types, one encompassing people smoking cigarettes and the other consisting of cigarette paraphernalia. We used two cue presentation times, 1000 and 2000 milliseconds (ms).ResultsCues of people smoking cigarettes elicited greater AB than cues of cigarette paraphernalia across both subject groups when cues were presented for 2000 ms, but not 1000 ms. PLWHA who smoke exhibited greater AB for cues of people smoking cigarettes than cigarette paraphernalia when presented for 2000 ms compared to people with OUD who smoke.ConclusionThe addition of social cues potentiates cigarette cue AB, based on cue type and stimulus presentation time. Understanding the neurobiology of this relationship can help design treatments that can target AB and prevent relapse.
Current situation of the hospitalization of persons without family in Japan and related medical challenges
Authors: Yamazaki Sayaka , Tamiya Nanako , Muto Kaori , Hashimoto Yuki , Yamagata Zentaro 
Published: September 2022

AbstractThis study aims to determine the approximate number of hospitalizations of persons without family and the medical challenges they encounter in hospitals across Japan. Self-administered questionnaires were mailed to 4,000 randomly selected hospitals nationwide to investigate the actual conditions and problems, decision-making processes, and use of the government-recommended Guidelines for the hospitalization of, and decision-making support for, persons without family. To identify the characteristics of each region and hospital function, chi-square tests were used to make separate group comparisons by hospital location and type. Responses were received from 1,271 hospitals (31.2% response rate), of which 952 hospitals provided information regarding the number of admissions of persons without family. The mean (SD) and median number of hospitalizations (approximate number per year) of patients without family was 16 (79) and 5, respectively. Approximately 70% of the target hospitals had allowed the hospitalization of a person without family. The most common difficulties encountered during the hospitalization were collecting emergency contact information, decision-making related to medical care, and discharge support. In the absence of family members and surrogates, the medical team undertook the decision-making process, which was commonly performed according to manuals and guidelines and by consulting an ethics committee. Regarding the use of the government-recommended Guidelines, approximately 70% of the hospitals that were aware of these Guidelines responded that they had never taken any action based on these Guidelines, with significant differences by region and hospital type. To solve the problems related to the hospitalization of persons without family, the public should be made aware of these Guidelines, and measures should be undertaken to make clinical ethics consultation a sustainable activity within hospitals.
Chromosome-scale genome assembly of a Japanese chili pepper landrace, Capsicum annuum ‘Takanotsume’
Authors: Shirasawa Kenta , Hosokawa Munetaka , Yasui Yasuo , Toyoda Atsushi , Isobe Sachiko 
Published: September 2022

AbstractHere, we report the genome sequence of a popular Japanese chili pepper landrace, Capsicum annuum ‘Takanotsume’. We used long-read sequencing and optical mapping, together with the genetic mapping technique, to obtain the chromosome-scale genome assembly of ‘Takanotsume’. The assembly consists of 12 pseudomolecules, which corresponds to the basic chromosome number of C. annuum, and is 3,058.5 Mb in size, spanning 97.0% of the estimated genome size. A total of 34,324 high-confidence genes were predicted in the genome, and 83.4% of the genome assembly was occupied by repetitive sequences. Comparative genomics of linked-read sequencing-derived de novo genome assemblies of two Capsicum chinense lines and whole-genome resequencing-derived genome assemblies of Capsicum species revealed not only nucleotide sequence variations but also genome structure variations (i.e., chromosomal rearrangements) between ‘Takanotsume’ and its relatives. Overall, the genome sequence data generated in this study will accelerate the pan-genomics and breeding of Capsicum, and facilitate the dissection of genetic mechanisms underlying the agronomically important traits of ‘Takanotsume’.
Artificializing accounting numbers: a sensemaking perspective in times of crisis
Authors: Hoang Nhung Thi Hong 
Published: September 2022

PurposeThe purpose of this paper is to study how people use competing accounting numbers to make sense of and legitimize actions in a complex environment in times of crisis.Design/methodology/approachThis paper analyzes the implementation of a standardized budget model at a USA intergovernmental organization, by relying on a triangulation of data sources, including face-to-face interviews, direct observations, and archival documents. The organization faces one of the greatest crises it has ever experienced. An accounting team and a human resources team make sense differently the same reality–staffing. The sensemaking perspective framework is utilized to provide a theoretical structure for the analysis.FindingsThe understudied organization undergoes constant evolution during the budgetary crisis; data reveal different forms of cues, which activate the sensemaking process, such as fading and compressed cues. Although compressed cues subsequently emerge, they play a more crucial role in managers' enactment than pre-existing fading cues. Artificializing accounting numbers refer to the social process of constructing compressed cues or artificial artifacts that are neither wrong nor right, neither soft nor hard and not useful for peoples' sensemaking but used to legitimize managers' strategic decisions.Practical implicationsThis artificializing process explains the people's resistance to policy implementation. Furthermore, the multiplicity of cues provides useful information for regulators and managers to understand uncertainty during a crisis.Originality/valueThis study presents a rare case of an international third sector organization amid a budgetary crisis. Among few studies referring to numbers as sensemaking resources, this study focuses on the importance of systematic power and corporate power relative to the process of sensemaking.
Adaptability capacity framework for sustainable practices in the Ghanaian construction industry
Authors: Pim-Wusu Mark , Aigbavboa Clinton , Thwala Wellington Didibhuku 
Published: September 2022

PurposeThe urgent need to preserve the ecosystem, which faces a threat from non-environmentally-friendly anthropogenic activities, has led to the study of adaptive capacity implementation. There is an indication that the construction industries in developed countries are relatively better equipped to pursue sustainable construction than those in the developing world. Despite this, sustainable construction is yet to be established in developing countries. This research aims to develop a framework to drive and enable small and medium-sized (SME) firms in Ghana to implement adaptive capacity.Design/methodology/approachThe study adopted a quantitative approach, and 400 responses were retrieved as a sample size for which a six-factor adaptive capacity implementation framework was arrived at for SMEs in the Ghanaian construction industry. The data gathered from the respondents were analysed using IBM SPSS version 26 and AMOS version 24, and a structural equation modelling was also used to determine the work's validity based on the AMOS software.FindingsThe findings revealed that education and training, government support and a centralised information hub significantly influence adaptive capacity outcomes in Ghana.Practical implicationsIt is recommended that the government, corporate and professional institutions that desire to preserve the country's ecosystem be guided by this study's adaptive capacity implementation framework.Originality/valueThis study's novelty also lies in the integrated framework for adaptive capacity implementation developed to aid small- and medium- sized enterprises in Ghana's construction industry to ensure environmentally-friendly construction activities.
Entrepreneurial marketing of small and medium-sized suppliers enhancing technological capability: lessons from industrial suppliers in South Korea
Authors: Sun Yongwook , Lee Euehun 
Published: September 2022

PurposeRapid changes in technologies and customer preferences are increasing market uncertainty. Hence, despite the benefits of reactive and adaptive marketing in the industrial market, such marketing is sometimes insufficient for suppliers to survive and succeed. This phenomenon is prevalent among the small and medium-sized suppliers (SMSs) who fail to build technological capability. This suggests that SMSs should be entrepreneurial to survive and succeed in today’s environment. Against this backdrop, the purposes of this study are to understand the process by which entrepreneurial marketing of SMSs enhances their technological capability and to explore factors that stimulate SMSs to implement entrepreneurial marketing.Design/methodology/approachBased on a survey data set on 249 industrial SMSs in South Korea, the authors test the hypotheses formulated in this work using structural equation modeling.FindingsBased on effectuation theory, this study conceptualizes entrepreneurial marketing as a process by contrasting entrepreneurial marketing with reactive and adaptive marketing. The results show that proactive market orientation and subsequent exploratory market behavior enhance technological capability, and proactive market orientation is stimulated by relational satisfaction and perceived technological turbulence.Originality/valueThis study advances effectuation theory in the industrial marketing literature by exploring the value of entrepreneurial marketing in today’s industrial market. Further, this study extends the entrepreneurial marketing literature by conceptualizing and testing the process by which entrepreneurial marketing of SMSs enhances their technological capability.
Effects of marketization on the evolution of firms' R&D efficiency: evidence from China
Authors: Zhang Qingyu , Chen Xiude , Cao Mei 
Published: September 2022

PurposePrevious studies demonstrate that market-oriented reform has contributed significantly to China's economic growth from the efficiency-based economic view. But some argue that state-owned firms have access to policy information, scarce resources, and government support, and thus state-owned firms might foster innovation. This study tries to find out either market force or state ownership helps improve firms' R&D efficiency.Design/methodology/approachUsing data from China's high-tech industry, we employed the fixed-effect stochastic frontier model and the spatial panel Han-Philips linear dynamic regression model to investigate the relationship between market-oriented reform and the dynamic evolution of R&D efficiency in both temporal and spatial dimensions. Moreover, we examined whether the relationship is affected in a state-owned economy and an industry protection environment.FindingsThe results indicate the following: (1) the R&D efficiency of China's high-tech industry has improved steadily and has converged gradually across its regions during the market-oriented reform; (2) the marketization degree is positively correlated with R&D efficiency and its regional convergence; (3) the state-owned economy and industry protection have significantly weakened the ability of market forces to shape R&D efficiency — i.e. they reduce, rather than enhance, R&D efficiency.Originality/valueThis investigation helps understand the drivers of R&D efficiency in transition economies, and the findings are also helpful in defining the boundaries and constraints of market forces.
Developing Islamic sustainable and responsible investment criteria: an overview
Authors: Haji Wahab Muhammad Zarunnaim , Mohamed Naim Asmadi 
Published: September 2022

Purpose
The purpose of this study is to explore the necessity for developing Islamic sustainable and responsible investment (i-SRI) criteria based on environmental, social and governance issues.

Design/methodology/approach
To address the above objective, this study adopted a qualitative method via content document analysis and interviews with experts.

Findings
Based on the analysis, this study discovered five primary aspects that lead to the necessity for developing i-SRI criteria. First, Malaysia has yet to develop i-SRI criteria. Second, the absence of i-SRI criteria will eventually lead to Shariah issues. Third, any Islamic financial instrument is bound to encounter numerous issues and challenges, thereby making it difficult to be marketed globally if it does not have a proper and standardized framework. Fourth, the establishment of i-SRI criteria can serve as a key reference point for the players in the industry, including investors, policymakers and other parties. Finally, the development of i-SRI criteria can play a vital role in enhancing the current Islamic capital market products offering in Malaysia.

Practical implications
There are several implications identified in this study. First, continuous research on the i-SRI criteria can offer numerous benefits to the regulatory bodies and policymakers who can use the findings in their decision-making process. Second, in terms of investors, the results can help them to make better investment choices by referring to the i-SRI criteria. Third, this study will be valuable to the academicians in terms of opportunity to explore a new research area, i.e. the i-SRI criteria, besides adding to the extant literature on this topic which is still scant currently.

Originality/value
This study discovered five primary aspects that lead to the necessity for developing i-SRI criteria.