bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phyletic distribution and diversification of the Phage Shock Protein stress response system in bacteria and archaea
Authors: Popp Philipp F. , Gumerov Vadim M. , Andrianova Ekaterina P. , Bewersdorf Lisa , Mascher Thorsten , Zhulin Igor B. , Wolf Diana 
Published: February 2021

AbstractThe bacterial cell envelope is an essential structure that protects the cell from environmental threats, while simultaneously serving as communication interface and diffusion barrier. Therefore, maintaining cell envelope integrity is of vital importance for all microorganisms. Not surprisingly, evolution has shaped conserved protection networks that connect stress perception, transmembrane signal transduction and mediation of cellular responses upon cell envelope stress. The phage shock protein (PSP) stress response is one of such conserved protection networks. Most of the knowledge about the Psp response comes from studies in the Gram-negative model bacterium,Escherichia coliwhere the Psp system consists of several well-defined protein components. Homologous systems were identified in representatives of Proteobacteria, Actinobacteria, and Firmicutes; however, the Psp system distribution in the microbial world remains largely unknown. By carrying out a large-scale, unbiased comparative genomics analysis, we found components of the Psp system in many bacterial and archaeal phyla and demonstrated that the PSP system deviates dramatically from the proteobacterial prototype. Two of its core proteins, PspA and PspC, have been integrated in various (often phylum-specifically) conserved protein networks during evolution. Based on protein sequence and gene neighborhood analyses ofpspAandpspChomologs, we built a natural classification system of PSP networks in bacteria and archaea. We performed a comprehensivein vivoprotein interaction screen for the PSP network newly identified in the Gram-positive model organismBacillus subtilisand found a strong interconnected PSP response system, illustrating the validity of our approach. Our study highlights the diversity of PSP organization and function across many bacterial and archaeal phyla and will serve as foundation for future studies of this envelope stress response beyond model organisms.
The genome of the CTG(Ser1) yeast Scheffersomyces stipitisis plastic
Authors: Estevez Samuel Vega , Armitage Andrew , Bates Helen J. , Harrison Richard J. , Buscaino Alessia 
Published: February 2021

ABSTRACTMicroorganisms need to adapt to environmental changes, and genome plasticity can lead to rapid adaptation to hostile environments by increasing genetic diversity. Here, we investigate genome plasticity in the CTG(Ser1) yeastScheffersomyces stipitis, an organism with an enormous potential for second-generation biofuel production. We demonstrate thatS. stipitishas an intrinsically plastic genome and that differentS. stipitisisolates have genomes with distinct chromosome organisation. Real-time evolution experiments show thatS. stipitisgenome plasticity is common and rapid as extensive genomic changes with fitness benefits are detected followingin vitroevolution experiments. Hybrid MinION Nanopore and Illumina genome sequencing identifies retrotransposons as major drivers of genome diversity. Indeed, the number and position of retrotransposons is different in differentS. stipitisisolates, and retrotransposon-rich regions of the genome are sites of chromosome rearrangements. Our findings provide important insights into the adaptation strategies of the CTG (Ser1) yeast clade and have critical implications in the development of second-generation biofuels. These data highlight that genome plasticity is an essential factor to be considered for the development of sustainableS. stipitisplatforms for second-generation biofuels production.
Clinical and Genetic insights in a tertiary care center cohort of patients with bicuspid aortic valve
Authors: Théron Alexis , Touil Anissa , Résseguier Noémie , Collod-Beroud Gwenaelle , Norscini Giulia , Simoni Anne-Sophie , Odelin Gaёlle , Collart Frédéric , Zaffran Stéphane , Avierinos Jean-François 
Published: February 2021

ABSTRACTBACKGROUNDto describe spectrum of valve function in bicuspid aortic valve (BAV) patients referred to a tertiary care center and to investigate genetic pathways associated with valve degeneration.METHODSAll consecutive patients with BAV were prospectively included from 2014 to 2018. BAV was defined according to embryologic and Sievers classifications. Clinical and echo variables were compared according to aortic valve function. Aortic valve tissues were collected from BAV patients (n=15) operated for severe aortic stenosis (AS-BAV, n=7) or aortic regurgitation (AR-BAV, n=8). RT-qPCR was performed to compare gene expression level in AS-BAV, AR-BAV and controls corresponding to healthy tricuspid aortic valves collected on human heart explant immediately after transplantation (n=5).RESULTSOut of 223 adults with BAV, mean age 53±17 years, 83% had left-right coronary cusps fusion, 80% Sievers type 1 BAV and 49% aortopathy. Twenty-four patients had normal valve function, 66 patients had AS-BAV, 91 patients had AR-BAV and 40 patient had AR+AS BAV. BAV phenotype did not predict neither AS-BAV nor AR-BAV (all p>0.1). By multivariable analysis, age >50 (41.6[10.3-248.2],p<0.001) and presence of raphe(12.8[2.4-87.4],p<0.001) were significantly associated with AS-BAV and male gender of AR-BAV(5[1.6-16.4], p=0.005). RT-qPCR revealed overexpression ofRUNX2in AS-BAV (17.67±1.83 vs 3.25±0.93, p=0.04), and overexpression ofCOL1A1(4.01±0.6vs2.25±0.5,p=0.03) andFLNA(23.31±7.5vs1.97±0.3,p=0.03) in AR-BAV.CONCLUSIONSThis prospective study confirmed high prevalence of valve dysfunction at first diagnosis of BAV in a referred population. Clinical and echo variables are poorly associated with BAV dysfunction. The leaking or stenotic processes could be both supported by dysregulation of specific genetic pathways
Metaplasia of respiratory and digestive tissues in the Eastern oysterCrassostrea virginicaassociated with the Deepwater Horizon oil spill
Authors: Roopnarine Deanne S. , Roopnarine Peter D. , Anderson Laurie C. , Hwang Ji Hae , Patel Swati 
Published: February 2021

AbstractMetaplasia is a well documented and deleterious effect of crude oil components on bivalved molluscs, including oysters. This reversible transformation of one cell type to another, is a common response to petroleum-product exposure in molluscs. It has been shown experimentally in previous work that eastern oysters (Crassostrea virginica) exposed to petroleum products will exhibit metaplasia of digestive tissues. Here we document for the first time that wild adult oysters inhabiting coastal waters in the northern Gulf of Mexico during and in the aftermath of the Deepwater Horizon oil spill (2010) exhibited metaplasia in both ctenidia and digestive epithelia at significantly higher levels than geographic controls ofC. virginicafrom Chesapeake Bay. Both ctenidial (respiratory and suspension feeding) and digestive tract tissues exhibited significantly higher frequencies of metaplasia in specimens from the Gulf of Mexico compared to those from Chesapeake Bay. Metaplasia included the loss of epithelial cilia, transformations of columnar epithelia, hyperplasia and reduction of ctenidial branches, and vacuolization of digestive tissues. Evidence for a reduction of metaplasia following the oil spill (2010-2013) is suggestive but equivocal.
Dual MAPK and HDAC inhibition rewires the apoptotic rheostat to trigger colorectal cancer cell death
Authors: Jenkins Laura J. , Luk Ian Y. , Palmieri Michelle , Fairlie W. Douglas , Lee Erinna F. , Schoffer Kael L. , Tan Tao , Ng Irvin , Vukelic Natalia , Tse Janson W.T. , Nightingale Rebecca , Alam Zakia , Iatropoulos George , Ernst Matthias , Afshar-Sterle Shoukat , Desai Jayesh , Gibbs Peter , Sieber Oliver M. , Dhillon Amardeep S. , Tebbutt Niall C. , Mariadason John M. 
Published: February 2021

AbstractThe EGFR/RAS/MEK/ERK signalling pathway (ERK/MAPK) is hyper-activated in most colorectal cancers (CRCs). A current limitation of inhibitors of this pathway is that they primarily induce cytostatic effects in CRC cells. Nevertheless, these drugs do induce expression of pro-apoptotic factors, suggesting they may prime CRC cells to undergo apoptosis. As histone deacetylase inhibitors (HDACi) induce expression of multiple pro-apoptotic proteins, we examined whether they could synergize with ERK/MAPK inhibitors to trigger CRC cell apoptosis. Combined MEK/ERK and HDAC inhibition synergistically induced apoptosis in CRC cell lines and patient-derived tumour organoids in vitro, and attenuated Apc-initiated adenoma formation in vivo. Mechanistically this effect was mediated through induction of the BH3-only pro-apoptotic proteins BIM and BMF. Importantly, we demonstrate that this treatment paradigm can be tailored to specific MAPK genotypes in CRCs, by combining HDACi with EGFR, KRASG12C or BRAFV600 inhibitors in KRAS/BRAFWT; KRASG12C, BRAFV600E CRC cell lines respectively. These findings identify a novel ERK/MAPK genotype-targeted treatment paradigm for colorectal cancer.
Venomics and antivenomics of Indian spectacled cobra (Naja naja) from the Western Ghats
Authors: Vanuopadath Muralidharan , Raveendran Dileepkumar , Nair Bipin Gopalakrishnan , Sadasivan Nair Sudarslal 
Published: February 2021

AbstractVenom proteome profiling ofNaja najafrom the Western Ghats region in Kerala was achieved through SDS-PAGE and RP-HPLC followed by Q-TOF LC-MS/MS analysis, incorporating PEAKS and Novor assistedde novosequencing methodologies. A total of 115 proteins distributed across 17 different enzymatic and non-enzymatic venom protein families were identified through conventional and 39 peptides through homology-driven proteomics approaches. Fourteen peptides derived throughde novocomplements the Mascot data indicating the importance of homology-driven approaches in improving protein sequence information. Among the protein families identified, glutathione peroxidase and endonuclease were reported for the first time in the Indian cobra venom. Immunological cross-reactivity assessed using Indian polyvalent antivenoms suggested that VINS showed better EC50(2.48 μg/mL) value than that of PSAV (6.04 μg/mL) and Virchow (6.03 μg/mL) antivenoms. Western blotting experiments indicated that all the antivenoms elicited poor binding specificities, especially towards low molecular mass proteins. Second-generation antivenomics studies revealed that VINS antivenom was less efficient to detect many low molecular mass proteins such as three-finger toxins and Kunitz-type serine protease Inhibitors. Taken together, the present study enabled a large-scale characterization of the venom proteome ofNaja najafrom the Western Ghats and emphasized the need for developing more efficient antivenoms.HighlightsProteomics of cobra venom resulted in the identification of 115 proteins representing 17 snake venom protein families.De novoapproaches exclusively yielded 39 peptides harbouring multiple amino acid mutations.Glutathione peroxidase and endonuclease were identified for the first time in Indian cobra venom.Indian polyvalent antivenoms showed varying cross-reactivity towards cobra venom.VINS antivenom was less efficient to detect many low molecular mass proteins (< 20 kDa).
Hidden Talents: Poly (I:C)-induced maternal immune activation improves mouse visual discrimination performance and reversal learning in a sex-dependent manner
Authors: Zhao Xin , Tran Hieu , DeRosa Holly , Roderick Ryland C. , Kentner Amanda C. 
Published: February 2021

AbstractWhile there is a strong focus on the negative consequences of maternal immune activation (MIA) on developing brains, very little attention is directed towards potential advantages of early life challenges. In this study we utilized a polyinosine-polycytidylic acid (poly(I:C)) MIA model to test visual discrimination (VD) and reversal learning (RL) in mice using touchscreen technology. Significant sex differences emerged in that MIA reduced the latency for males to make a correct choice in the VD task while females reached criterion sooner, made fewer errors, and utilized fewer correction trials in RL compared to saline controls. These surprising improvements were accompanied by the sex-specific upregulation of several genes critical to cognitive functioning, indicative of compensatory plasticity in response to MIA. In contrast, when exposed to a ‘two-hit’ stress model (MIA + loss of the social component of environmental enrichment (EE)), mice did not display anhedonia but required an increased number of PD and RL correction trials. These animals also had significant reductions of CamK2a mRNA in the prefrontal cortex. Appropriate functioning of synaptic plasticity, via mediators such as this protein kinase and others, are critical for behavioral flexibility. Although EE has been implicated in delaying the appearance of symptoms associated with certain brain disorders, these findings are in line with evidence that it also makes individuals more vulnerable to its loss. Overall, with the right ‘dose’, early life stress exposure can confer at least some functional advantages, which are lost when the number or magnitude of these exposures become too great.
Constraints and opportunities facing construction organization in post-conflict condition in Afghanistan
Authors: Amarkhil Qais , Elwakil Emad 
Published: February 2021

Purpose
Although there are many challenges and constraints for construction organization operation and performance in a post-conflict condition, there is insufficient construction project management literature. Therefore, the purpose of this paper is to identify a framework to understand and determine critical constraints and opportunities in a post-conflict condition facing local construction firms in Afghanistan. The proposed framework is composed of three major steps: identify and determine key performance indicators; identify challenges impacting organization operation and performance in post-conflict condition; determine critical constraints and opportunities based on prioritized performance measures; and organizational strength and weakness factors.

Design/methodology/approach
The strength, weakness, opportunities and threat matrix analysis has been used to determine post-conflict condition constraints and opportunities. Then the analytical hierarchy process has been used to prioritize the measures and identify the constraints and opportunities facing construction companies in a post-conflict situation. The mix-research method is applied to this study to analyse qualitative variables and quantitative variables obtained from the experts’ opinions and 51 filled questioners.

Findings
The study shows that there are a total of 11 critical constraints and three essential opportunities for construction companies that industry practitioners and policymakers should take into account while formulating the organizational strategy.

Practical implications
The developed framework will benefit construction companies in improving their performance and operation in after-conflict conditions.

Originality/value
This paper is the first to provide a comprehensive conceptualization of the challenges and constraints for construction organization operation and performance in a post-conflict condition. It also offers a novel conceptual framework to understand and determine critical constraints and opportunities in a post-conflict condition facing local construction firms in Afghanistan.
Reducing the risks of endoscopic sinonasal surgery in the Covid‐19 era
Authors: Leong Samuel C. , Mogre Dilesh , Andrews Peter , Davies Elgan 
Published: February 2021

AbstractObjectivesMany routine sinonasal procedures utilising powered instruments are regarded as aerosol‐generating. This study aimed to assess how different instrument settings affect detectable droplet spread and patterns of aerosolised droplet spread during simulated sinonasal surgery in order to identify mitigation strategies.DesignSimulation series using three‐dimensional (3‐D) printed sinonasal model. Fluorescein droplet spread was assessed following microdebriding and drilling of fluorescein‐soaked grapes and bones, respectively.SettingUniversity dry lab.Participants3‐D printed sinonasal model.Main outcome measuresPatterns of aerosolised droplet spread.Results and ConclusionThere were no observed fluorescein droplets or splatter in the measured surgical field after microdebridement of nasal polyps at aspecific irrigation rate and suction pressure. Activation of the microdebrider in the presence of excess fluid in the nasal cavity (reduced or blocked suction pressure, excessive irrigation fluid or bleeding) resulted in detectable droplet spread. Drilling with either coarse diamond or cutting burs resulted in detectable droplets and greater spread was observed when drilling within the anterior nasal cavity. High‐speed drilling is a high‐risk AGP but the addition of suction using a third hand technique reduces detectable droplet spread outside the nasal cavity. Using the instrument outside the nasal cavity inadvertently, or when unblocking, produces greater droplet spread and requires more caution.
First experience of POLARx™ versus Arctic Front Advance™: An early technology comparison
Authors: Creta Antonio , Kanthasamy Viijayabharathy , Schilling Richard J. , Rosengarten James , Khan Fakhar , Honarbakhsh Shohreh , Earley Mark J. , Hunter Ross J. , Finlay Malcom 
Published: February 2021

AbstractIntroductionCryoballoon ablation is an established technique to achieve pulmonary vein isolation in patients with atrial fibrillation (AF). Recently, a new manufacturer of cryoballoon achieved regulatory CE marking (POLARx™; Boston Scientific). We describe our early experience of using this new market entrant of the technology and describe procedural aspects in comparison to the incumbent Medtronic Arctic Front Advance™.MethodsWe assessed the first 40 AF ablations performed with the POLARx catheter at the Barts Heart Centre. These patients were compared with a contemporaneous series of patients undergoing ablation by the same operators using the Arctic Front Advance. Procedural metrics were prospectively recorded.ResultsA total of four operators undertook 40 cases using the POLARx catheter, compared with 40 cases using the Arctic Front Advance. Procedure times (60.0 vs. 60.0 min) were similar between the two technologies, however left atrial dwell time (35.0 vs 39.0 min) and fluoroscopy times (3.3 vs. 5.2 min) were higher with the POLARx. Measured nadir and isolation balloon temperatures were significantly lower with POLARx. Almost all veins were isolated with a median freezing time of 16.0 (POLARx) versus 15.0 (Arctic Front Advance) min. The rate of procedural complications was low in both groups.ConclusionThe POLARx cryoballoon is effective for pulmonary vein isolation. Measured isolation and nadir temperatures are lower compared with the predicate Arctic Front Advance catheter. The technology appears similar in acute efficacy and has a short learning curve, but formal dosing studies may be required to prove equivalence of efficacy.
Nursing students’ experience and training in healthcare aid during the COVID‐19 pandemic in Spain
Authors: Hernández‐Martínez Antonio , Rodríguez‐Almagro Julián , Martínez‐Arce Alejandro , Romero‐Blanco Cristina , García‐Iglesias Juan Jesús , Gómez‐Salgado Juan 
Published: February 2021

BackgroundDuring the COVID‐19 pandemic health crisis, in some countries such as Spain, nursing students have offered to provide health assistance, but the role they have played, their degree of preparedness to face the situation, and what must be improved in their training to be ready for these situations is unknown.ObjectiveDescribe the experience and perceptions of students of the Nursing university degree during their participation as health support in the COVID‐19 health crisis in Spain.DesignWe conducted a cross‐sectional survey study.Method503 students enrolled in the 4th course of the Nursing degree in Spain during the months of March and April 2020. An online questionnaire was developed, based on a pilot study and distributed through the Nursing Association, students’ unions and students’ associations. Variables were used to describe their participation, degree of preparedness and training needs to determine how to improve training through descriptive statistics, as well as nonparametric tests to analyse the relationship between training and degree of preparedness nursing students. Results are reported according to the STROBE Statement.Results73.2% (368) of students offered to participate in healthcare aid, of which 225 were actively involved. 27.8% carried out nursing tasks without supervision, and 47.7% assisted COVID‐19 patients as any other nurse. Only 3.4% felt very prepared to work in the field of intensive care, finding that those students who perceived a higher degree of preparedness had received previous training in personal protective equipment and mechanical ventilation (p < 0.005). The highest scores for training activities that may improve their preparedness were simulations to improve levels of anxiety and stress when managing critical patients, simulation in ventilatory support and mandatory practices in services where ventilators are used.ConclusionsAlthough three out of four students were willing to provide health assistance, they recognise that they were not specially prepared in the field of intensive care and demand training with simulation to improve anxiety and stress levels in the management of critical patients and simulation in ventilatory support.Relevance to clinical practiceStudents have been vital resources for our health system and society when they have been needed. It is now up to us, both teachers and health authorities, to share their efforts by implementing the necessary improvements in training and safety measures not only because these affects the health and safety of the patient, but because they will be essential parts in future pandemics.
Strategic and cultural contexts of real options reasoning in innovation portfolios
Authors: Kaufmann Carsten , Kock Alexander , Gemünden Hans Georg 
Published: February 2021

AbstractDecision makers find creating an innovation portfolio challenging, because more innovative projects are associated with a higher degree of uncertainty. In this study, we investigate the potential benefits of applying real options reasoning (ROR) in innovation portfolio management from an attention‐based view. Using a sample of 137 innovation portfolios with multiple informants, we investigate ROR's influence on portfolio innovativeness and, ultimately, on portfolio success in a mediated model. Further, we analyze the moderating influence of an innovation portfolio's organizational context—entrepreneurial orientation and innovation climate—on ROR's application. The results support ROR's positive relationship to portfolio innovativeness and portfolio success. The analysis also supports the positive interaction between entrepreneurial orientation and ROR with respect to portfolio innovativeness. This study contributes to the literature by demonstrating the relationship between ROR and portfolio success, mediated by portfolio innovativeness. In addition, the study's analysis offers an explanation of previously mixed findings regarding ROR's benefits by considering the firm's strategic and cultural innovation contexts. The findings underline the relevance of strategic support for ROR's effectiveness in innovation portfolio management. Furthermore, the findings encourage managers to implement ROR, but also stress the essential contribution an entrepreneurial orientation makes when the managers do so.