bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional unit and regulatory mechanisms of supergene in female-limited Batesian mimicry ofPapilio polytes
Authors: Komata Shinya , Yoda Shinichi , KonDo Yûsuke , Shinozaki Souta , Tamai Kouki , Fujiwara Haruhiko 
Published: February 2022

AbstractSupergenes are sets of genes and genetic elements that are inherited like a single gene and control complex adaptive traits, but their functional roles and units are poorly understood. InPapilio polytes, female-limited Batesian mimicry is thought to be regulated by a ~130kb inversion region (highly diversified region: HDR) containing three genes,UXT,U3Xanddoublesex(dsx) which switches non-mimetic and mimetic types. To determine the functional unit, we here performed electroporation-mediated RNAi analyses (and further Crispr/Cas9 forUXT) of genes within and flanking the HDR in pupal hindwings. We first clarified that non-mimeticdsx-hhad a function to switch from male to non-mimetic female and onlydsx-Hisoform 3 had an important function in the formation of mimetic traits. Next, we found thatUXTwas involved in making mimetic type pale-yellow spots and adjacent genesir2removed excess red spots in hindwings, both of which refine more elaborate mimicry. Furthermore, downstream gene networks ofdsx, U3XandUXTscreened by RNA sequencing showed thatU3Xupregulateddsxexpression and repressedUXTexpression. These findings demonstrate that a set of multiple genes, not only inside but also flanking HDR, can function as supergene members, which extends the definition of supergene unit than we considered before. Also, our results indicate thatdsx-Hfunctions as the switching gene and some other genes such asUXTandsir2within the supergene unit work as the modifier gene.Article summarySupergenes are thought to control complex adaptive traits, but their detailed function are poorly understood. InPapilio polytes, female-limited Batesian mimicry is regulated by an ~130kb inversion region (highly divergent region: HDR) containing three genes. Our functional analysis showed thatdoublesexswitches the mimicry polymorphism, and that an inside geneUXTand an outside genesir2to the HDR work to refine more elaborate mimicry. We here succeed in defining the unit of mimicry supergene and some novel modifier genes.
Mucosal Immunization of Cynomolgus Macaques with Adenoviral Vector Vaccine Elicits Neutralizing Nasal and Serum Antibody to Several SARS-CoV-2 Variants
Authors: Flitter Becca A. , Lester Colin A. , Tedjakusuma Sarah N. , Dora Emery G. , Peinovich Nadine , Cortese Mario , Martinez Clarissa I. , Jegede Clara B. , Neuhaus Elena D. , Tucker Sean N. 
Published: February 2022

AbstractThe emergence of SARS-CoV-2 variants continues to be a major obstacle for controlling the global pandemic. Despite the currently authorized SARS-CoV-2 vaccines ability to reduce severe disease and hospitalization, new immunization strategies are needed that enhance mucosal immune responses, inhibit community transmission, and provide protection against emerging variants. We have developed a mucosally delivered, non-replicating recombinant adenovirus vector (rAd5) vaccine, that has proven efficacy in the clinic against other respiratory viruses [1]. Here we evaluated the immunogenicity of three candidate SARS-CoV-2 vaccines in cynomolgus macaques that contained spike (S) and/or nucleocapsid (N) from either the Wuhan or the beta variant to select a candidate for future clinical development. Mucosal immunization with the Wuhan specific S vaccine (ED90) induced significant cross-reactive serum IgG responses against to Wuhan, beta, gamma and delta lineages, and generated substantial serum neutralizing activity. In nasal samples, ED90 immunization induced 1000-fold increases in IgA to all variants of concern tested and had neutralizing activity against Wuhan and delta. While immunization with the beta specific vaccine (ED94) enhanced IgG and IgA responses to homologous beta variant S and RBD, this approach resulted in less cross-reactive responses to other variants in the serum and nasal passages compared to ED90. As ED90 immunization induced the most robust cross-reactive systemic and mucosal antibody responses, this candidate was chosen for future clinical development.
222-nm far UVC exposure results in DNA damage and transcriptional changes to mammalian cells
Authors: Ong Qunxiang , Wee Winson , Cruz Joshua Dela , Teo J. W. Ronnie , Han Weiping 
Published: February 2022

SummaryUltraviolet (UV) germicidal tools have recently gained attention as a disinfection strategy against the COVID-19 pandemic but the safety profile arising from their exposure have been controversial and impeded larger scale implementation. We compare the emerging 222-nm far UVC and 277-nm UVC LED disinfection modules with the traditional UVC mercury lamp emitting at 254 nm to understand their effects on human retinal cell line ARPE-19 and HEK-A keratinocytes. Cells illuminated with 222-nm far UVC survived while those treated with 254-nm and 277-nm wavelengths underwent apoptosis via JNK/ATF2 pathway. However, cells exposed to 222-nm far UVC presented the highest degree of DNA damage as evidenced by yH2AX staining. Globally, these cells presented transcriptional changes in cell cycle and senescence pathways. Thus, the introduction of 222-nm far UVC lamps for disinfection purposes should be carefully considered and designed with the inherent dangers involved.
Phylogenetic Network Dissimilarity Measures That Take Branch Lengths Into Account
Authors: Yakici Berk A. , Ogilvie Huw A. , Nakhleh Luay 
Published: February 2022

AbstractDissimilarity measures for phylogenetic trees have long been used for analyzing inferred trees and understanding the performance of phylogenetic methods. Given their importance, a wide array of such measures have been developed, some of which are based on the tree topologies alone, and others that also take branch lengths into account. Similarly, a number of dissimilarity measures of phylogenetic networks have been developed in the last two decades. However, to the best of our knowledge, all these measures are based solely on the topologies of phylogenetic networks and ignore branch lengths. In this paper, we propose two phylogenetic network dissimilarity measures that take both topology and branch lengths into account. We demonstrate the behavior of these two measures on pairs of related networks. Furthermore, we show how these measures can be used to cluster a set of phylogenetic networks obtained by an inference method, illustrating this application on the posterior sample of phylogenetic networks. Both measures are implemented in the publicly available software package PhyloNet.
Feasibility of a novel non-invasive swab technique for serial whole-exome sequencing of cervical tumors during chemoradiation therapy
Authors: Bronk Julianna K. , Kapadia Chiraag , Wu Xiaogang , Chapman Bhavana V. , Wang Rui , Karpinets Tatiana V. , Song Xingzhi , Futreal Andrew M. , Zhang Jianhua , Klopp Ann H. , Colbert Lauren E. 
Published: February 2022

AbstractBackgroundClinically relevant genetic predictors of radiation response for cervical cancer are understudied due to the morbidity of repeat invasive biopsies required to obtain genetic material. Thus, we aimed to develop a novel noninvasive cervical swab technique to collect tumor DNA with adequate throughput to perform whole-exome sequencing (WES) at serial time points over the course of chemoradiation therapy (CRT).MethodsCervical cancer tumor samples from patients undergoing chemoradiation were collected at baseline, at week 1, week 3, and at the completion of CRT (week 5) using a noninvasive swab-based biopsy technique. Swab samples were analyzed with whole-exome sequencing (WES) with mutation calling using a custom pipeline optimized for shallow whole-exome sequencing with low tumor purity. Tumor mutation changes over the course of treatment were profiled.Results217 samples were collected and successfully sequenced for 70 patients. A total of 33 patients had a complete set of samples at all four time points. The mean mapping rate was 98% for all samples, and the mean target coverage was 180. Overall mutation frequency decreased during CRT with disease response but mapping rate and mean target coverage remained at >98% and >180 reads at week 5.ConclusionThis study demonstrates the feasibility and application of a noninvasive swab-based technique for WES analysis to investigate dynamic tumor mutational changes during treatment and may be a valuable approach to identify novel genes which confer radiation resistance.
Somatostatin Neurons in the Bed Nucleus of the Stria Terminalis Play a Sex-Dependent Role in Binge Drinking
Authors: Nair Malini Suresh , Dao Nigel C. , Melean Daniela Lopez , Griffith Keith R. , Starnes W. David , Moyer J. Brody , Sicher Avery R. , Brockway Dakota F. , Meeks Kathleen D. , Crowley Nicole A 
Published: February 2022

ABSTRACTAlcohol use disorder (AUD) is characterized by alcohol use coupled with chronic relapse and involves brain regions including the bed nucleus of the stria terminalis (BNST). Here, we explore whether a subpopulation of BNST neurons, somatostatin (SST) expressing GABAergic neurons, play a role in an animal model of binge-like alcohol consumption, the Drinking in the Dark (DID) model. Chemogenetic activation of BNST SST neurons reduced binge alcohol consumption in female but not male SST-Cre mice, while inhibition of these neurons in the same mice had no effect. In addition, chemogenetic activation of these neurons did not cause apparent changes in models of anxiety-like behavior in either sex. Basal SST cell counts and intrinsic excitability of SST neurons were compared to attempt to understand sex differences in DREADD-induced changes in drinking, and while males had a greater number of BNST SST neurons, this effect went away when normalizing for total BNST volume. Together, these results suggest SST neurons in the BNST should be further explored as a potential neuronal subtype modulated by AUD, and for their therapeutic potential.HIGHLIGHTSChemogenetic activation of BNST SST neurons reduces binge drinking in female but not male miceChemogenetic activation of these neurons has no effect on anxiety-like behavior in either sexElectrophysiology revealed no clear sex differences in intrinsic excitability BNST SST neurons between males and femalesImaging revealed males had greater overall BNST SST cell numbers than females, but this effect could be explained by normalizing for total BNST volume
A novel analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray
Authors: Iwasaki Mai , Lefevre Arthur , Althammer Ferdinand , Łąpieś Olga , Hilfiger Louis , Kerspern Damien , Melchior Meggane , Küppers Stephanie , Krablicher Quirin , Patwell Ryan , Herpertz Sabine C , Ditzen Beate , Schönig Kai , Bartsch Dusan , Stern Javier E. , Darbon Pascal , Grinevich Valery , Charlet Alexandre 
Published: February 2022

AbstractThe hypothalamic neuropeptide, oxytocin (OT), exerts prominent analgesic effects via central and peripheral action. Here we discovered a novel subset of OT neurons whose projections preferentially terminate on OT receptor (OTR)-expressing neurons in the ventrolateral periaqueductal gray (vlPAG). Using a newly generated line of transgenic rats (OTR-IRES-Cre), we determined that most of the vlPAG OTR expressing cells being targeted by OT projections are GABAergic in nature. Both optogenetically-evoked axonal OT release in the vlPAG as well as chemogenetic activation of OTR vlPAG neurons results in a long-lasting overall increase of vlPAG neuronal activity. This then leads to an indirect suppression of sensory neuron activity in the spinal cord and strong analgesia. Finally, we describe a novel OT→vlPAG→spinal cord circuit that seems critical for analgesia in the context of both inflammatory and neuropathic pain.Highlights- We generated a new transgenic knock-in rat line (OTR-IRES-Cre)- A distinct parvOT neuronal population projects to vlPAG but not the SON or spinal cord- OT excites vlPAG OTR neurons which indirectly inhibit SC WDR neurons- This novel parvOT→vlPAG→SC pathway alleviates nociception but not the affective component of pain
Extracellular RNA signatures of mutant KRAS(G12C) lung adenocarcinoma cells
Authors: Khojah Reem , Reggiardo Roman E. , Ozen Mehmet , Maroli Sreelakshmi Velandi , Carrillo David , Demirci Utkan , Kim Daniel H. 
Published: February 2022

ABSTRACTExtracellular RNAs (exRNAs) are actively secreted from cells in membrane-bound extracellular vesicles (EVs). Diverse classes of RNAs are secreted as exRNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and transposable element RNAs (TE RNAs). However, the full composition and clinical utility of exRNAs secreted in response to oncogenic signaling are unknown. Here we use both affinity- and nanofiltration-based EV isolation approaches to show that mutant KRAS(G12C) signaling results in the secretion of specific lncRNAs, TE RNAs, and mRNAs, some of which are prognostic for lung adenocarcinoma (LUAD) patient survival. We found that inhibition of KRAS(G12C) signaling broadly reprograms the noncoding transcriptome, as evidenced by a substantial increase in TE RNA secretion. KRAS(G12C) inhibition also increased the abundance of secreted lncRNAs and retained intron-containing transcripts, while decreasing the mRNA content of EVs. Oncogenic KRAS(G12C) signaling was required for the secretion of mRNAs from a set of 20 genes that are significantly associated with unfavorable clinical outcomes in LUAD. Our study suggests that both coding and noncoding RNAs that are secreted in EVs may serve as KRAS(G12C)-specific signatures for diagnosing lung cancer.
Actin turnover protects the cytokinetic contractile ring from structural instability
Authors: McDargh Zachary , Zhu Tianyi , Zhu Hongkang , O’Shaughnessy Ben 
Published: February 2022

AbstractIn common with other actomyosin contractile cellular machineries, actin turnover is required for normal function of the cytokinetic contractile ring. Cofilin is an actin-binding protein contributing to turnover by severing actin filaments, required for cytokinesis by many organisms. In fission yeast cofilin mutants, contractile rings suffer bridging instabilities in which actin bundles peel away from the plasma membrane into straight bridges. The origin of this behaviour is unclear. Here we used molecularly explicit simulations of the fission yeast contractile ring to examine the role of cofilin. Simulations reproduced the experimentally observed cycles of bridging and reassembly during constriction, each lasting ∼ 6 min, and the tendency for bridging to occur in ring segments with low myosin II Myo2 density. The lack of cofilin severing produced ∼ 2-fold longer filaments and, consequently, ∼ 2-fold higher ring tensions. Simulations identified bridging as originating in the boosted ring tension, which increased centripetal forces that detached actin from Myo2 that anchored actin to the membrane. Thus, cofilin serves a critical role in cytokinesis by protecting the contractile ring from bridging, the principal structural threat.Summary statementMolecularly explicit simulations showed that cofilin-mediated actin severing protects the fission yeast cytokinetic contractile ring from instabilities in which actin peels away into straight bridges.
The relationship between board characteristics and social responsibility with firm innovation
Authors: Shafeeq Nimr Al-Maliki Hind , Salehi Mahdi , Kardan Behzad 
Published: February 2022

PurposeThe present study aims to assess the potential impacts of board members' characteristics, including connectedness and independence, on the level of the firm's involvement in innovation and corporate social responsibility (CSR).Design/methodology/approachVariables of board members' interlock and independence are selected for measuring the board characteristics and their association with innovation. The range of disclosure of social responsibility (SR) of the firms inside and outside the industries is also analyzed through descriptive-correlational. The selected sample includes 280 firm-years listed firms on Iraq Stock Exchange during 2012–2017 and 1,026 firm-years on the Tehran Stock Exchange. The hypotheses are examined using multivariate regression models and panel data.FindingsThe observations show that board interlock and independence in both countries are willing to improve firms' innovation. Moreover, having controlled the industry index, the authors find that business environment innovation is willing to be transmitted into the firms through outside industry sources in Iran. In the Iraq country, regardless of industry index, the positive association between interlocked boards and firm innovation is established. Further analyses also articulate that board interlock is not considered a mechanism to transmit information and experiences about CSR activities.Originality/valueThis paper is a pioneer study to assess the relationship between board member characteristics and the firms' innovation and SR both in Iran and Iraq. Also, it extends the literature by considering the industry index as a significant source of knowledge and experience to gain more precise results. Therefore, the current paper may contribute to the development of knowledge in this field of study.
Quality-driven university curriculum reform in Zimbabwe: a critical conceptualisation of harmonised minimum bodies of knowledge
Authors: Phuthi Nduduzo 
Published: February 2022

PurposeThe surging demand for higher education in Africa for expedited socio-economic growth and global sustainable development demands customising gains made elsewhere for local benefit through quality provision. This study contributes to local and international discourses on the refinement of results-based university learning content determination on the lines of the Bologna Process, and advocates the development of situationally relevant curricula for successful national advancement in Zimbabwe.Design/methodology/approachThe qualitative study uses records and documentary analysis, interviews and meetings with key participants involved in shaping academic processes at one of the country's young and fragile universities. The introspective research approach enabled the cumulative experiential and reflective contributions of participants to shape both the dialogue and follow-up action on the adoption of minimum bodies of knowledge in university curriculum reform.FindingsParticipants celebrated efforts to pit harmonisation alongside autonomy in academic discourses, and suggested improvements on the mechanisms to define policy and operational frameworks for diversely-oriented academic establishments. They lauded and interrogated the discourse around minimum bodies of knowledge, calling for further critical research and analysis for defining clarity on its harmonisation function.Originality/valueThis paper traverses the rapidly expanding Zimbabwe higher education system's endeavours to regulate mandates and operations, in pursuit of relevance, quality and excellence and examines stakeholder efforts at determining streamlined university curricula. It contributes uniquely to collective regulation of multiple institutions towards quality academic agendas that underpin the life-long competences of the institutions' graduates.
Joint market participation choices of smallholder farmers and households’ welfare: evidence from Senegal
Authors: Camara Alhassane , Goundan Anatole , Henning Christian , Savard Luc , Beye Assane 
Published: February 2022

PurposeThere is much evidence in the literature showing the benefits of input market participation on farmers’ welfare. The same is true for participation in marketing. However, there are very few studies on the expected benefit of input market participation and marketing. This study fills this gap by examining the issue in the Senegalese context for food and cash crops.Design/methodology/approachThe authors estimate a multinomial endogenous switching regression using a highly detailed 2017 agricultural survey in Senegal. They first identify factors that shape farmers’ decision to participate in the input market and marketing and then assess the impact of market participation choices on farmers’ profits.FindingsThe results show that the most profitable market participation regime depends on the crop under consideration. For food crops, joint participation in markets maximizes profit per hectare, while for groundnuts, the main cash crop in Senegal, participation in the input market is not necessary to maximize farm profit.Research limitations/implicationsUsing panel data would improve the quality of estimations (time-variant effects) and help to consider the role of risk in output and input markets.Originality/valueThis paper helps to characterize different profiles of farmers based on their market participation and crop choices and provide policymakers with recommendations for maximizing farmers’ profit.
Patterns of export shipments
Authors: Yang Xuebing 
Published: February 2022

PurposeThis paper studies the frequency and the average size of export shipments at the firm–product–destination level.Design/methodology/approachThis paper sets up a theoretical model about the shipping frequency and the shipment size of exports to a given market from individual exporters. Then it confronts the predictions of the model with trade data.FindingsThis paper shows that patterns of export shipments are determined by (1) a product's export potential in a market, which is the exports revenue when the firm delivers the exports of the product to the market in a single shipment in each period; and (2) factors related to the firm's efficiency of managing shipments of the product exported to the market.Originality/valueThis paper reveals some important patterns of export shipments. It provides a theoretical model that explains the patterns.
How human resource managers can prevent perceived pandemic threats from escalating into diminished change-oriented voluntarism
Authors: De Clercq Dirk , Pereira Renato 
Published: February 2022

PurposeFor human resource (HR) managers, the harmful outcomes of employees’ ruminations about external crises, such as a pandemic, represent important, timely concerns. This research postulates that employees’ perceptions of pandemic threats might diminish the extent to which they engage in change-oriented voluntarism at work. This negative connection may be attenuated by employees’ access to two personal (work-related self-efficacy and organization-based self-esteem) and two relational (goal congruence and interpersonal harmony) resources.Design/methodology/approachThe theoretical predictions are tested with survey data collected among employees who work in a banking organization in Portugal.FindingsPersistent negative thoughts about a pandemic undermine discretionary efforts to alter and enhance the organizational status quo, but this detrimental effect is mitigated when employees (1) feel confident about their work-related abilities, (2) have a positive self-image about their organizational functioning, (3) share a common mindset with coworkers with respect to work goals and (4) maintain harmonious relationships with coworkers.Practical implicationsThis study pinpoints several ways HR managers can reduce the danger that employees’ worries about life-threatening crises may lead to complacent responses that, somewhat paradoxically, might undermine their ability to alleviate the suffered hardships.Originality/valueThe findings contribute to research on the impact of external crisis situations on organizations by providing an explanation of why employees may avoid productive, disruptive work activities, contingent on their access to complementary resources.