bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity and determinants of recombination landscapes in flowering plants
Authors: Brazier Thomas , Glémin Sylvain 
Published: March 2022

AbstractDuring meiosis, crossover rates are not randomly distributed along the chromosome and therefore they locally influence the creation of novel genotypes and the efficacy of selection. To date, the broad diversity of recombination landscapes among plants has rarely been investigated, undermining the overall understanding of the constraints driving the evolution of crossover frequency and distribution. The determinants that shape the local crossover rate and the diversity of the resulting landscapes among species and chromosomes still need to be assessed in a formal comparative genomic approach. We gathered genetic maps and genomes for 57 flowering plant species, corresponding to 665 chromosomes, for which we estimated large-scale recombination landscapes. Chromosome length drives the basal recombination rate for each species, but within species we were intrigued to notice that the chromosome-wide recombination rate is proportional to the relative size of the chromosome. Moreover, for larger chromosomes, crossovers tend to accumulate at the ends of the chromosome leaving the central regions as recombination-free regions. Based on identified crossover patterns and testable predictions, we proposed a conceptual model explaining the broad-scale distribution of crossovers where both telomeres and centromeres are important. Finally, we qualitatively identified two recurrent crossover patterns among species and highlighted that these patterns globally correspond to the underlying gene distribution. In addition to the positive correlation between recombination and gene density, we argue that crossover patterns are essential for the efficiency of chromosomal genetic shuffling, even though the ultimate evolutionary potential forged by the diversity of recombination landscapes remains an open question.
External validation of risk scores to predict in-hospital mortality in patients hospitalized due to coronavirus disease 2019
Authors: Hassan Shermarke , Ramspek Chava L. , Ferrari Barbara , van Diepen Merel , Rossio Raffaella , Knevel Rachel , Mura Vincenzo la , Artoni Andrea , Martinelli Ida , Bandera Alessandra , Nobili Alessandro , Gori Andrea , Blasi Francesco , Canetta Ciro , Montano Nicola , Rosendaal Frits R. , Peyvandi Flora ,   LUMC-COVID-19 Research Group,   COVID-19 Network working group
Published: March 2022

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) presents an urgent threat to global health. Prediction models that accurately estimate mortality risk in hospitalized patients could assist medical staff in treatment and allocating limited resources.AimsTo externally validate two promising previously published risk scores that predict in-hospital mortality among hospitalized COVID-19 patients.MethodsTwo cohorts were available; a cohort of 1028 patients admitted to one of nine hospitals in Lombardy, Italy (the Lombardy cohort) and a cohort of 432 patients admitted to a hospital in Leiden, the Netherlands (the Leiden cohort). The primary endpoint was in-hospital mortality. All patients were adult and tested COVID-19 PCR-positive. Model discrimination and calibration were assessed.ResultsThe C-statistic of the 4C mortality score was good in the Lombardy cohort (0.85, 95CI: 0.82-0.89) and in the Leiden cohort (0.87, 95CI: 0.80-0.94). Model calibration was acceptable in the Lombardy cohort but poor in the Leiden cohort due to the model systematically overpredicting the mortality risk for all patients. The C-statistic of the CURB-65 score was good in the Lombardy cohort (0.80, 95CI: 0.75-0.85) and in the Leiden cohort (0.82, 95CI: 0.76-0.88). The mortality rate in the CURB-65 development cohort was much lower than the mortality rate in the Lombardy cohort. A similar but less pronounced trend was found for patients in the Leiden cohort.ConclusionAlthough performances did not differ greatly, the 4C mortality score showed the best performance. However, because of quickly changing circumstances, model recalibration may be necessary before using the 4C mortality score.
Development and Implementation of a Simple and Rapid Extraction-Free Saliva SARS-CoV-2 RT-LAMP Workflow for Workplace Surveillance
Authors: Li Zhiru , Bruce Jacqueline L. , Cohen Barry , Cunningham Caileigh V. , Jack William E. , Kunin Katell , Langhorst Bradley W. , Miller Jacob , Moncion Reynes A. , Poole Catherine B. , Premsrirut Prem K. , Ren Guoping , Roberts Richard J. , Tanner Nathan A. , Zhang Yinhua , Carlow Clotilde K. S. 
Published: March 2022

AbstractEffective management of the COVID-19 pandemic requires widespread and frequent testing of the population for SARS-CoV-2 infection. Saliva has emerged as an attractive alternative to nasopharyngeal samples for surveillance testing as it does not require specialized personnel or materials for its collection and can be easily provided by the patient. We have developed a simple, fast, and sensitive saliva-based testing workflow that requires minimal sample treatment and equipment. After sample inactivation, RNA is quickly released and stabilized in an optimized buffer, followed by reverse transcription loop-mediated isothermal amplification (RT-LAMP) and detection of positive samples using a colorimetric and/or fluorescent readout. The workflow was optimized using 1,670 negative samples collected from 172 different individuals over the course of 6 months. Each sample was spiked with 50 copies/μL of inactivated SARS-CoV-2 virus to monitor the efficiency of viral detection. Using pre-defined clinical samples, the test was determined to be 100% specific and 97% sensitive, with a limit of detection comparable to commercially available RT-qPCR-based diagnostics. The method was successfully implemented in a CLIA laboratory setting for workplace surveillance and reporting. From April 2021-February 2022, more than 30,000 self-collected samples from 755 individuals were tested and 85 employees tested positive mainly during December and January, consistent with high infections rates in Massachusetts and nationwide. The rapid identification and isolation of infected individuals with trace viral loads before symptom onset minimized viral spread in the workplace.
Human endogenous retrovirus activation contributes to biliary atresia pathogenesis through re-education of resident macrophages
Authors: Sheng Jianpeng , Zhang Junlei , Zhao Yaxing , Song Jinyuan , Tang Jianghui , Wang Xun , Ji Yongtao , Wu Jiangchao , Li Taohong , Zhang Hui , Tano Vincent , Langley Sarah Raye , Bai Xueli , Liang Tingbo 
Published: March 2022

AbstractBiliary atresia (BA) is a life-threatening neonatal fibro-inflammatory disease characterized by hepatic fibrosis, cirrhosis, and end-stage liver failure. BA is also the most frequent indication of pediatric liver transplantation globally. Despite the devastating condition of BA, the pathogenesis mechanism is unknown. Viral infection has been suggested to be associated with BA, but definitive evidence to support this hypothesis is not available. To elucidate the virus-associated pathogenesis mechanism of BA and to understand the immune ecosystem, we performed single-cell transcriptomic and proteomic profiling of BA livers. We detected human endogenous virus (HERV) in infants with BA and their parents. HERV was mainly found in FOLR2+resident macrophages, T cells, and NK cells. In addition, HERV activation re-educated the fetal-derived FOLR2+resident macrophages, and reactive oxygen species scavenging neutrophil recruitment was impaired in patients with BA and HERV+, due to FOLR2+resident macrophage re-education. Furthermore, we showed depletion of FOLR2+resident macrophage and N-acetylcysteine treatment could rescue the liver damage in BA. Overall, our study revealed the HERV-associated immunopathology mechanism of BA. These results contribute to potential diagnosis and immunotherapy strategies for BA.
Members of Venezuelan Equine Encephalitis Complex entry into host cells by clathrin-mediated endocytosis in a pH-dependent manner
Authors: Ghietto Lucia Maria , Gil Pedro Ignacio , Quinteros Paloma Olmos , Gomez Emiliano , Piris Franco Martin , Kunda Patricia , Contigiani Marta , Paglini Maria Gabriela 
Published: March 2022

AbstractPixuna virus (PIXV) and Río Negro virus (RNV) are mosquito-borne alphaviruses belonging to the Venezuelan Equine Encephalitis (VEE) complex, which includes pathogenic epizootic and enzootic subtypes responsible for life-threatening diseases in equines. Considering that the first steps in viral infection are crucial for the efficient production of new progeny, the aim of this study was to elucidate the early events of the replication cycle of these two viruses. To this end, we used chemical inhibitors and the expression of dominant-negative constructs to study the dependence of clathrin and endosomal pH on PIXV and RNV internalization mechanisms. We demonstrated that both viruses are internalized primarily via clathrin-mediated endocytosis, where the low pH in endosomes is crucial for viral replication. Contributing knowledge regarding the entry route of VEE complex members is important to understand the pathogenesis of these viruses and also to develop new antiviral strategies.
Comparing flickering and pulsed chromatic pupil light responses
Authors: Tripolone Constanza , Issolio Luis , Agüero Carlos , Lavaque Alejandro , Cao Dingcai , Barrionuevo Pablo 
Published: March 2022

AbstractProtocols for chromatic pupil light reflex (PLR) testing considered mostly pulsed stimulation (pPLR). A more sophisticated and promising technique is based on the PLR to flickering stimulation (fPLR). Our aim was to compare fPLR and pPLR parameters in order to validate fPLR paradigm. Two different experiments were carried out in young participants to compare parameters of chromatic pupillary measurements under flickering and pulsed conditions. We found that the fPLR amplitude parameter was significantly associated with pPLR transient constriction parameter. Also, for some conditions, typical pulse parameters can be identified directly in the fPLR recordings.
Antecedent effect models as an exploratory tool to link climate drivers to herbaceous perennial population dynamics data
Authors: Compagnoni Aldo , Childs Dylan , Knight Tiffany M. , Gómez Roberto Salguero- 
Published: March 2022

AbstractUnderstanding mechanisms and predicting natural population responses to climate is a key goal of Ecology. However, studies explicitly linking climate to population dynamics remain limited. Antecedent effect models are a set of statistical tools that capitalize on the evidence provided by climate and population data to select time windows correlated with a response (e.g., survival, reproduction). Thus, these models can serve as both a predictive and exploratory tool. We compare the predictive performance of antecedent effect models against simpler models, and showcase their exploratory analysis potential by selecting a case study with high predictive power. We fit three antecedent effect models: (1) weighted mean models (WMM), which weigh the importance of monthly anomalies based on a Gaussian curve, (2) stochastic antecedent models (SAM), which weigh the importance of monthly anomalies using a Dirichlet process, and (3) regularized regressions using the Finnish Horseshoe prior (FHM), which estimate a separate effect size for each monthly anomaly. We compare these approaches to a linear model using a yearly climatic predictor and a null model with no predictors. We use demographic data from 77 natural populations of 34 plant species ranging between seven and 36 years of length. We then fit models to the asymptotic population growth rate (λ) and its underlying vital rates: survival, development, and reproduction. We find that models including climate do not consistently outperform null models. We hypothesize that the effect of yearly climate is too complex, weak, and confounded by other factors to be easily predicted using monthly precipitation and temperature data. On the other hand, in our case study, antecedent effect models show biologically sensible correlations between two precipitation anomalies and multiple vital rates. We conclude that, in temporal datasets with limited sample sizes, antecedent effect models are better suited as exploratory tools for hypothesis generation.Open Research statementData and code to reproduce the analyses are available on zenodo athttps://dx.doi.org/10.5281/zenodo.7839199.
The cancer chemotherapeutic 5-fluorouracil is a potent inhibitor of Fusobacterium nucleatum and its activity is modified by the intratumoral microbiota
Authors: LaCourse Kaitlyn D. , Baryiames Alexander , Kempchinsky Andrew G. , Johnston Christopher D. , Bullman Susan 
Published: March 2022

AbstractFusobacterium nucleatum is among the most prevalent and dominant bacterial species in colorectal cancer (CRC) tumor tissue, and growing evidence supports its role in cancer progression and poorer patient prognosis. Here we perform a small molecule inhibitor screen of 1,846 bioactive compounds against a CRC isolate of F. nucleatum and find that 15% of inhibitors are antineoplastic agents including fluoropyrimidines. Validation of these findings reveal that 5-fluorouracil (5-FU), the first-line chemotherapeutic used to treat CRC worldwide, is a potent inhibitor of F. nucleatum CRC isolates at concentrations found in serum of CRC patients treated with 5-FU. We also identify members of the intratumoral microbiota that are resistant to 5-FU, including Escherichia coli. Further, CRC E. coli isolates can modify 5-FU and relieve 5-FU toxicity towards otherwise-sensitive F. nucleatum and human CRC epithelial cells. Lastly, we demonstrate that ex-vivo CRC tumor microbiota from patients undergo different levels of community disruption after 5-FU exposure and have the potential to deplete 5-FU levels, thereby reducing local drug efficacy. Together, these observations argue for further investigation into the role that the CRC intratumoral microbiota plays in patient response to chemotherapy.
Systematic dissection of phosphorylation-dependent YAP1 complex formation elucidates a key role for PTPN14 in Hippo signal integration
Authors: Uliana Federico , Ciuffa Rodolfo , Mishra Ranjan , Fossati Andrea , Frommelt Fabian , Mehnert Martin , Birkeland Eivind Salmorin , Peter Matthias , Tapon Nicolas , Aebersold Ruedi , Gstaiger Matthias 
Published: March 2022

ABSTRACTCellular signaling relies on the temporal and spatial control of the formation of transient protein complexes by post-translational modifications, most notably by phosphorylation. While several computational methods have been developed to predict the functional relevance of phosphorylation sites, assessing experimentally the interdependency between protein phosphorylation and protein-protein interactions (PPIs) remains a major challenge. Here, we describe an experimental strategy to establish interdependencies between specific phosphorylation events and complex formation. This strategy is based on three main steps: (i) systematically charting the phosphorylation landscape of a target protein; (ii) assigning distinct proteoforms of the target protein to different protein complexes by electrophoretic separation of native complexes (BNPAGE) and protein/phopho correlation profiling; and (iii) genetically deleting known regulators of the target protein to identify which ones are required for given proteoforms and complexes. We applied this strategy to study phosphorylation- dependent modulation of complexes containing the transcriptional co-regulator YAP1. YAP1 is highly phosphorylated and among the most extensively connected proteins in the human interactome. It functions as the main signal integrator and effector protein of the Hippo pathway which controls organ size and tissue homeostasis. Using our workflow, we could identify several distinct YAP1 proteoforms specifically associated with physically distinct complexes and infer how their formation is affected by known Hippo pathway members. Importantly, our findings suggest that the tyrosine phosphatase PTPN14 controls the co-transcriptional activity of YAP1 by regulating its interaction with the LATS1/2 kinases. In summary, we present a powerful strategy to establish interdependencies between specific phosphorylation events and complex formation, thus contributing to the “functionalization” of phosphorylation events and by this means provide new insights into Hippo signaling.
Tension anisotropy drives phenotypic transitions of cells via two-way cell-ECM feedback
Authors: Alisafaei Farid , Shakiba Delaram , Iannucci Leanne E. , Davidson Matthew D. , Pryse Kenneth M. , Chao Pen-hsiu Grace , Burdick Jason A. , Lake Spencer P. , Elson Elliot L. , Shenoy Vivek B. , Genin Guy M. 
Published: March 2022

AbstractMechanical factors such as stress in the extracellular environment are known to affect phenotypic commitment of cells. However, the stress fields experienced by cells in tissues are multiaxial, and the ways that cells integrate this multiaxial information are largely unknown. Here, we report that the anisotropy of these stress fields is a critical factor triggering phenotypic transition in fibroblast cells, outweighing the previously reported role of stress amplitude. Using a combined experimental and computational approach, we discovered a self-reinforcing mechanism in which cellular protrusions interact with collagen fibers to develop tension anisotropy, which in turn stabilizes protrusions and amplifies their contractile forces. Disruption of this self-reinforcing process, either by reducing tension anisotropy or by inhibiting contractile protrusions, prevented phenotypic conversion of fibroblasts to contractile myofibroblasts.
A surface pocket in the cytoplasmic domain of the herpes simplex virus fusogen gB controls membrane fusion
Authors: Pataki Zemplen , Sanders Erin K. , Heldwein Ekaterina E. 
Published: March 2022

ABSTRACTMembrane fusion during the entry of herpesviruses is carried out by the viral fusogen gB that is activated by its partner protein gH. Unusually, the fusogenic activity of gB is controlled by its cytoplasmic (or intraviral) domain (gBCTD) and, according to the current model, the gBCTDis a trimeric, inhibitory clamp that restrains gB in the prefusion conformation. But how the gBCTDclamp is released by gH is unclear. Here, we identified two new regulatory elements within gB and gH from the prototypical herpes simplex virus 1: a surface pocket within the gBCTDand residue V831 within the gH cytoplasmic tail. Mutagenesis and structural modeling suggest that gH V831 interacts with the gB pocket. The gB pocket is located above the “fault line” between adjacent protomers, and we hypothesize that insertion of the gH V831 wedge into the pocket serves to push the protomers apart. This releases the inhibitory clamp on the gB prefusion conformation and activates gB fusogenic activity. Both gB and gH are conserved across all herpesviruses, and this activation mechanism could be used by other gB homologs. Our proposed mechanism emphasizes a central role for the cytoplasmic regions in regulating the activity of a viral fusogen.AUTHOR SUMMARYHerpes simplex virus 1 (HSV-1) establishes lifelong infections in over a half of people and causes diseases ranging from oral or genital sores to blindness and brain inflammation. No vaccines or curative treatments are currently available. To infect cells, HSV-1 must first penetrate them by merging its lipid envelope with the membrane of the target cell. This process requires the collective actions of several viral and cellular proteins, notably, viral glycoproteins B and H (gB and gH). gH is thought to activate the fusogenic function of gB, but how the two proteins interact is unclear. Here, using mutational analysis, we have identified two new functional elements within the cytoplasmic regions of gB and gH: a surface pocket in gB and a single residue in gH, both of which are important for membrane fusion. Based on structural modeling, we propose that the gB pocket is the binding site for the gH residue, and that their interaction activates gB to cause membrane fusion. These findings extend our knowledge of the HSV-1 membrane fusion mechanism. Mechanistic understanding of HSV-1 entry is essential for understanding its pathogenesis and developing new strategies to prevent infections.
Learning from sales and operations planning process implementation at ASTRO Inc.
Authors: Tchokogué Andre , Ngniatedema Thomas , Pache Gilles 
Published: March 2022

PurposeThe purpose of this case study is to develop a complete understanding of the sales and operations planning (S&OP) process implementation effort at ASTRO Inc. and to determine the influential factors that led to its success, the interrelationship between them, as well as the level of influence of each factor compared to their counterparts. As we trace the evolution of S&OP in the organizational context, the view that its implementation leads to a positive impact in changing the way companies do business is not in itself novel. To date, there is limited academic investigation on how and why the S&OP process implementation leads to a successful organizational transformation.Design/methodology/approachThe data used in this case study were collected through semi-structured interviews with selected employees and through documentary analyses based on the archives at ASTRO Inc., a large North American company, for the period from 2016 to 2018. The paper adopts a methodology based on a retrospective study and interviews.FindingsThe analysis shows that the S&OP process design and its implementation required efforts on many distinct but complementary fronts to be successful. However, the level of influence varies across the organizational enablers that contribute to this success. Its successful implementation is fundamentally dependent on the managers' ability to create mindset changes in the organizational culture, and to plan and coordinate the S&OP process deployment. The key enablers need to be skillfully combined, taking into account the contextual variables, namely, the company's internal context, the company's external context and the specific characteristics of the industry in which the company belongs.Originality/valueThe current study provides a better understanding of the implementation of the S&OP process and highlights the key enablers that led to its successful implementation. It provides practical managerial guidelines for designing, deploying and using an S&OP process in response to and in anticipation of customer demands, and competitive pressures.
Load frequency control based on an improved Chimp optimization algorithm using adaptive weight strategy
Authors: K. Ranjitha , P. Sivakumar , M. Monica 
Published: March 2022

Purpose
This study aims to implement an improved version of the Chimp algorithm (IChimp) for load frequency control (LFC) of power system.

Design/methodology/approach
This work was adopted by IChimp to optimize proportional integral derivative (PID) controller parameters used for the LFC of a two area interconnected thermal system.

Findings
The supremacy of proposed IChimp tuned PID controller over Chimp optimization, direct synthesis-based PID controller, internal model controller tuned PID controller and recent algorithm based PID controller was demonstrated.

Originality/value
IChimp has good convergence and better search ability. The IChimp optimized PID controller is the proposed controlling method, which ensured better performance in terms of converging behaviour, optimizing controller gains and steady-state response.