bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maximize crop production and environmental sustainability: insights from an ecophysiological model of plant-pest interactions and multi-criteria decision analysis
Authors: Zaffaroni Marta , Bevacqua Daniele 
Published: March 2022

AbstractSatisfying the demand for agricultural products while also protecting the environment from negative impacts of agriculture is a major challenge for crop management. We used an ecophysiological model of plant-pest interaction and multi-criteria decision analysis to optimize crop management when considering two contrasting objectives: (1) maximizing crop production and (2) minimizing environmental impact related to fertilization, irrigation and pesticide deployment. The model provides an indicator of crop production for 27 management scenarios, obtained combining three levels of fertilization, irrigation and pesticide use, respectively. We computed the environmental impact relevant to each management scenario by means of a weighted sum of costs assigned to fertilization, irrigation and pesticide use. We identified the optimal scenarios with respect to the considered objectives analysing the Pareto front. These scenarios were mostly characterized by high fertilization and no pesticide use. We evaluated the multi-functionality of the optimal scenarios by mean of the Gini coefficient: the scenario better assuring the equality between the two objectives was characterized by high fertilization, intermediate irrigation and no pesticide. Although our results remain qualitative and not immediately transferable to agronomic practices, our analytical framework provides a useful tool to evidence trade-offs among two contrasting objectives and provide solutions to act in an efficient way by leaving a certain degree of freedom to the political decision maker.
BRAF-V600E-Mediated Erk Activation Promotes Sustained Cell Cycling and Broad Transcriptional Changes in Neonatal Cardiomyocytes
Authors: Strash Nicholas , DeLuca Sophia , Janer Carattini Geovanni L. , Chen Yifan , Scherba Jacob , Jain Mehul , Naseri Ramona , Wu Tianyu , Bursac Nenad 
Published: March 2022

AbstractMitogens capable of promoting cardiomyocyte proliferation represent important targets for functional heart regeneration following myocardial infarction. We previously described an ERK-dependent pro-proliferative tissue phenotype following overexpression of constitutively-active (ca) human ERBB2 in both neonatal rat ventricular myocytes (NRVMs) and human iPSC-derived cardiomyocytes (hiPSC-CMs). Since ERBB2 canonically regulates multiple other pathways in addition to ERK, it is unclear whether ERK activation alone can drive CM proliferation. Here, we activated ERK in a targeted fashion by CM-specific lentiviral expression of a constitutively active mutant of BRAF, BRAF-V600E (caBRAF), in cultured NRVMs and examined the effects on engineered NRVM tissue proliferation, morphology, and function. caBRAF expression induced ERK activation, tissue growth, loss of contractile function, and increased tissue stiffness, all of which were sustained for at least 4 weeksin vitro. From bulk RNA-sequencing analysis of engineered tissues, we found that caBRAF had broad transcriptomic effects on CMs and induced a shift to glycolytic metabolism. Together, this work shows that direct ERK activation is sufficient to modulate CM cycling and functional maturation in a cell-autonomous fashion and could offer a potential target for cardiac regenerative therapies.
Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection
Authors: Taylor Lewis , Von Lendenfeld Felix , Ashton Anna , Sanghani Harshmeena , Tam Eric , Usselmann Laura , Veretennikova Maria , Dallmann Robert , McKeating Jane A , Vasudevan Sridhar , Jagannath Aarti 
Published: March 2022

ABSTRACTSleep and circadian rhythm disruption (SCRD), as encountered during shift work, increases the risk of respiratory viral infection including SARS-CoV-2. However, the mechanism(s) underpinning higher rates of respiratory viral infection following SCRD remain poorly characterised. To address this, we investigated the effects of acute sleep deprivation on the mouse lung transcriptome. Here we show that sleep deprivation profoundly alters the transcriptional landscape of the lung, causing the suppression of both innate and adaptive immune systems, disrupting the circadian clock, and activating genes implicated in SARS-CoV-2 replication, thereby generating a lung environment that promotes viral infection and associated disease pathogenesis. Our study provides a mechanistic explanation of how SCRD increases the risk of respiratory viral infections including SARS-CoV-2 and highlights therapeutic avenues for the prevention and treatment of COVID-19.
RdRp-scan: A Bioinformatic Resource to Identify and Annotate Divergent RNA Viruses in Metagenomic Sequence Data
Authors: Charon Justine , Buchmann Jan P. , Sadiq Sabrina , Holmes Edward C. 
Published: March 2022

ABSTRACTDespite a rapid expansion in the number of known RNA viruses following the advent of metagenomic sequencing, the identification and annotation of highly divergent RNA viruses remains challenging, particularly from poorly characterized hosts and environmental samples. Protein structures are more conserved than primary sequence data, such that structure-based comparisons provide an opportunity to reveal the viral “dusk matter”: viral sequences with low, but detectable, levels of sequence identity to known viruses with available protein structures. Here, we present a new open computational and resource – RdRp-scan – that contains a standardized bioinformatic toolkit to identify and annotate divergent RNA viruses in metagenomic sequence data based on the detection of RNA dependent RNA polymerase (RdRp) sequences. By combining RdRp-specific Hidden Markov models (HMM) and structural comparisons we show that RdRp-scan can efficiently detect RdRp sequences with identity levels as low as 10% to those from known viruses and not identifiable using standard sequence-to-sequence comparisons. In addition, to facilitate the annotation and placement of newly detected and divergent virus-like sequences into the known diversity of RNA viruses, RdRp-scan provides new custom and curated databases of viral RdRp sequences and core motif, as well as pre-built RdRp alignments. In parallel, our analysis of the sequence diversity detected by RdRp-scan revealed that while most of the taxonomically unassigned RdRps fell into pre-established clusters, some sequences cluster into potential new orders of RNA viruses related to the Wolframvirales and Tolivirales. Finally, a survey of the conserved A, B and C RdRp motifs within the RdRp-scan sequence database revealed additional variations of both sequence and position, which might provide new insights into the structure, function and evolution of viral RdRps.
Synaptotagmin 1 mediates toxicity of botulinum neurotoxin type A
Authors: Joensuu Merja , Lanoue Vanessa , Syed Parnayan , Wallis Tristan P. , Rae James , Blum Ailisa , Gormal Rachel , Small Christopher , Sanders Shanley , Jiang Anmin , Mahrhold Stefan , Krez Nadja , Cousin Michael , Cooper-White Ruby , Cooper-White Justin J. , Collins Brett M. , Parton Robert G. , Balistreri Giuseppe , Rummel Andreas , Meunier Frédéric A. 
Published: March 2022

AbstractThe extreme neurotoxicity of botulinum neurotoxins (BoNTs), broadly used as a therapeutics, is mediated by their direct binding to two plasma membrane receptors: polysialogangliosides (PSGs) and serotype-dependently either synaptotagmin 1/2 (Syt1/2) or synaptic vesicle glycoprotein 2 (SV2). Here, we demonstrate that although BoNT/A serotype binds directly to PSG and SV2, its neurotoxicity depends on Syt1. Using single-molecule superresolution microscopy of pathological concentrations of BoNT/A holotoxins, we demonstrate that the toxin binds to a preassembled PSG-Syt1 complex that forms nanoclusters with SV2 on the plasma membrane of hippocampal neurons. This coincidental interaction controls the selective endocytic targeting of BoNT/A into synaptic vesicles, leading to incapacitation of neuronal communication. Our results suggest that Syt1-SV2 plasma membrane nanoclusters may acts as a common target for various BoNT serotypes.One-Sentence SummaryBoNT/A hijacks an intrinsic tripartite PSG-Syt1-SV2 endocytic sorting mechanism to incapacitate neuronal communication
dSeqSb: A systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data
Authors: Dinarvand Mojdeh , Kock Forrest , Al Mouiee Daniel , Vuong Kaylee , Vijayan Abhishek , Tanzim Afia Fariha , Azad AKM , Penesyan Anahit , Castaño-Rodríguez Natalia , Vafaee Fatemeh 
Published: March 2022

AbstractInfection triggers a dynamic cascade of reciprocal events between host and pathogen wherein the host activates complex mechanisms to recognise and kill pathogens while the pathogen adjusts its virulence and fitness to avoid eradication by the host. The interaction between the pathogen and the host results in large-scale changes in gene expression in both organisms. Dual RNA-seq, the simultaneous detection of host and pathogen transcripts, has become a leading approach to unravel complex molecular interactions between the host and the pathogen and is particularly informative for intracellular organisms. The amount of in vitro and in vivo dual RNA-seq data is rapidly growing which demands computational pipelines to effectively analyse such data. In particular, holistic, systems-level, and temporal analyses of dual RNA-seq data are essential to enable further insights into the host-pathogen transcriptional dynamics and potential interactions. Here, we developed an integrative network-driven bioinformatics pipeline, dRNASb, a systems biology-based computational pipeline to analyse temporal transcriptional clusters, incorporate molecular interaction networks (e.g., protein-protein interactions), identify topologically and functionally key transcripts in host and pathogen, and associate host and pathogen temporal transcriptome to decipher potential between-species interactions. The pipeline is applicable to various dual RNA-seq data from different species and experimental conditions. As a case study, we applied dRNASb to analyse temporal dual RNA-seq data of Salmonella-infected human cells, which enabled us to uncover genes contributing to the infection process and their potential functions and to identify potential host-pathogen interactions between host and pathogen genes. Overall, dRNASb has the potential to identify key genes involved in bacterial growth or host defence mechanisms for future uses as therapeutic targets.
Neuronal miR-138 represses HSV-2 lytic infection by regulating viral and host genes with mechanistic differences compared to HSV-1
Authors: Chen Siyu , Deng Yue , Chen Hongjia , Lin Yuqi , Yang Xuewei , Sun Boqiang , Pan Dongli 
Published: March 2022

AbstractHerpes simplex virus 2 (HSV-2) establishes latent infection in dorsal root ganglion (DRG) neurons after productive (lytic) infection in peripheral tissues. A neuron-specific microRNA, miR-138, favors HSV-1 latency by repressing viral ICP0, and host Oct-1 and Foxc1 genes, yet the role of miR-138 in HSV-2 infection was unknown. The ICP0 mRNAs of HSV-1, HSV-2 and chimpanzee herpesvirus each have one to two canonical miR-138 binding sites. The sites are 100% conserved in 308 HSV-1 and 300 HSV-2 published sequences of clinical isolates. In co-transfection assays, miR-138 repressed HSV-2 ICP0 expression through the seed region and surrounding interactions that are different from HSV-1. An HSV-2 mutant with disrupted miR-138 binding sites on ICP0 showed increased ICP0 expression in Neuro-2a cells. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation confirmed miR-138 binding to HSV-2 ICP0, and identified UL19 and UL20 as additional targets, whose expression was repressed by miR-138 during co-transfection. In Neuro-2a cells, transfected miR-138 and its antagomir decreased and increased HSV-2 replication, respectively, and knockout experiment showed that miR-138’s host targets OCT-1 and FOXC1 were important for HSV-2 replication. In primary mouse DRG neurons, both ICP0 and FOXC1 positively regulated HSV-2 replication, but both overexpressed and endogenous miR-138 suppressed HSV-2 replication primarily by repressing ICP0 expression. Thus, miR-138 can suppress HSV-2 neuronal replication through multiple viral and host pathways. These results reveal functional similarities and mechanistic differences in how miR-138 regulates HSV-1 and HSV-2 infection and indicate an evolutionary advantage of using miR-138 to repress lytic infection in neurons.ImportanceHerpes simplex virus 1 (HSV-1) and HSV-2 are closely related viruses with major differences. Both viruses establish latency in neurons from which they reactivate to cause disease. A key aspect of HSV latency is repression of productive infection in neurons. Based on previous work with HSV-1, we investigated the role of a neuron-specific microRNA, miR-138, in HSV-2 infection, and established it as a repressor of HSV-2 productive infection in neuronal cells. This repression is mediated mainly by targeting viral ICP0 and host Foxc1 mRNAs, but other pathways also contribute. Despite functional conservation of the role of miR-138 between HSV-1 and HSV-2, many molecular mechanisms differ including how miR-138 represses ICP0 expression and miR-138 targeting of HSV-2 but not HSV-1 UL19 and UL20. To our knowledge, this study provides the first example of host microRNA regulation of HSV-2 infection.
Real-Time Flow Cytometry to assess qualitative and quantitative responses of oral pathobionts during exposure to antiseptics
Authors: Chatzigiannidou I. , Heyse J. , Props R. , Rubbens P. , Teughels W. , Van de Wiele T. , Boon N. 
Published: March 2022

AbstractAntiseptics are widely used in oral healthcare to prevent or treat oral diseases, such as gingivitis and periodontitis. However, the incidence of bacteria being tolerant to standard antiseptics has sharply increased over the last few years. This stresses the urgency for surveillance against tolerant organisms, as well as the discovery of novel antimicrobials. Traditionally, susceptibility to antimicrobials is assessed by broth micro-dilution or disc diffusion assays, both of which are time-consuming, labor-intensive and provide limited information on the mode of action of the antimicrobials. The above-mentioned limitations highlight the need for the development of new methods to monitor and further understand antimicrobial susceptibility. Here, we used real-time flow cytometry, combined with membrane permeability staining, as a quick and sensitive technology to study the quantitative and qualitative response of two oral pathobionts to different concentrations of chlorhexidine, cetylpyridinium chloride or triclosan. Apart from the real-time monitoring of cell damage, we further applied a phenotypic fingerprint method to differentiate between the bacterial subpopulations that arose due to treatment. We quantified the pathobiont damage rate of different antiseptics at different concentrations within 15 minutes of exposure and identified the conditions under which the bacteria were most susceptible. Moreover, we detected species-specific and treatment-specific phenotypic subpopulations. This proves that real-time flow cytometry can provide information on the susceptibility of different microorganisms in a short time frame while differentiating between antiseptics and thus could be a valuable tool in the discovery of novel antimicrobial compounds while at the same time deciphering their mode of action.
Transcriptomic clustering of critically ill COVID-19 patients
Authors: López-Martínez Cecilia , Martín-Vicente Paula , Gómez de Oña Juan , López-Alonso Inés , Gil-Peña Helena , Cuesta-Llavona Elías , Fernández-Rodríguez Margarita , Crespo Irene , Salgado del Riego Estefanía , Rodríguez-García Raquel , Parra Diego , Fernández Javier , Rodríguez-Carrio Javier , Dávalos Alberto , Chapado Luis A , Coto Eliecer , Albaiceta Guillermo M , Amado-Rodríguez Laura 
Published: March 2022

AbstractInfections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit (ICU), to identify two transcriptomic clusters characterized by expression of either interferon-related or immune checkpoint genes, respectively. These profiles have different ICU outcome, in spite of no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding similar results. These findings reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19, aimed to ultimately personalize their therapies.
Duration of viable virus shedding in SARS-CoV-2 omicron variant infection
Authors: Boucau Julie , Marino Caitlin , Regan James , Uddin Rockib , Choudhary Manish C. , Flynn James P. , Chen Geoffrey , Stuckwisch Ashley M. , Mathews Josh , Liew May Y. , Singh Arshdeep , Lipiner Taryn , Kittilson Autumn , Melberg Meghan , Li Yijia , Gilbert Rebecca F. , Reynolds Zahra , Iyer Surabhi L. , Chamberlin Grace C. , Vyas Tammy D. , Goldberg Marcia B. , Vyas Jatin M. , Li Jonathan Z. , Lemieux Jacob E. , Siedner Mark J. , Barczak Amy K. 
Published: March 2022

ABSTRACTClinical features of SARS-CoV-2 Omicron variant infection, including incubation period and transmission rates, distinguish this variant from preceding variants. However, whether the duration of shedding of viable virus differs between omicron and previous variants is not well understood. To characterize how variant and vaccination status impact shedding of viable virus, we serially sampled symptomatic outpatients newly diagnosed with COVID-19. Anterior nasal swabs were tested for viral load, sequencing, and viral culture. Time to PCR conversion was similar between individuals infected with the Delta and the Omicron variant. Time to culture conversion was also similar, with a median time to culture conversion of 6 days (interquartile range 4-8 days) in both groups. There were also no differences in time to PCR or culture conversion by vaccination status.
Viral cultures, Polymerase Chain Reaction Cycle Threshold Values and Viral Load Estimation for SARS-CoV-2 Infectious Potential Assessment in Hematopoietic Stem Cell and Solid Organ Transplant Patients: A Systematic Review
Authors: Jefferson Tom , Spencer Elizabeth A. , Conly John M. , Rosca Elena C. , Maltoni Susanna , Brassey Jon , Onakpoya Igho J. , Evans David H. , Heneghan Carl J. , Plüddemann Annette 
Published: March 2022

AbstractBackgroundOrgan transplant recipients are at increased vulnerability to SARS-CoV-2 due to immunosuppression and may pose a continued transmission risk especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation.ObjectivesWe performed a systematic review to investigate the relationship in transplant recipients between serial SARS-CoV-2 RT-PCR cycle threshold (Ct) value or cycle of quantification value (Cq), or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship.MethodsWe searched LitCovid, medRxiv, Google Scholar and WHO Covid-19 databases, from 1 November 2019 until 31 December 2021. We included studies reporting relevant data for transplantees with SARS-CoV-2 infection: results from serial RT-PCR testing and viral culture data from the same respiratory samples. We assessed methodological quality using five criteria, and synthesised the data narratively and graphically.ResultsWe included 10 case reports and case series reporting on 38 transplantees. We observed a relationship between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Two individuals shed replication-competent viruses over 100 days after infection onset. Lack of standardisation of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, most transplantees stopped shedding competent viruses when the RT-PCR cycle threshold was above 30 despite differences across platforms.ConclusionsViral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardised study design and reporting are essential to standardise guidance based on an increasing evidence base.
Efficacy of bladder training in adults with overactive bladder: A systematic review protocol
Authors: Lopes Rocha Anna Karoline , Monteiro Silvia Elizate , Volpato Maria P. , Paula e Silva Dinah Verleun de , Valim Lilian , Riccetto Cássio , Botelho Simone 
Published: March 2022

AbstractIntroductionThe aim of this systematic review will be to investigate and update whether bladder training can promote improvement of symptoms of overactive bladder syndrome with or without urgency urinary incontinence in adults.MethodsWe will perform a systematic review according to the Cochrane methodology of randomized controlled trials. An overall search strategy will be developed and adapted for each database. A bibliographic search will be conducted in eight databases - PubMed, PEDro, SciELO, LILACS, Cochrane Library, Web of Science, EMBASE, CINAHL, by manual searching. The MeSH terms will be “Bladder Training”, “Bladder Drill”, “Bladder Re-education”, “Bladder Retraining”, “Bladder Discipline”, “Overactive Bladder”, “Bladder, Overactive”, “Overactive Urinary Bladder”, “Urinary Bladder”, “Overactive, Urinary Bladder”, “Bladder, Urinary”, “Urinary Bladder Disease”, “Bladder Disease”, “Bladder Detrusor Muscle” and “Detrusor Muscle, Bladder”. Meta-analysis, if plausible, will be performed by the software Review Manager 5.4. Primary outcomes: symptoms of overactive bladder syndrome (urinary urgency with daytime voiding frequency, nocturia with or without urgency urinary incontinence), and cure/improvement assessed by instruments. Secondary outcomes: quality of life, functional assessment, validated scale/questionnaire and adverse events. Quality assessment will be performed by Cochrane instrument and quality of evidence will be assessed by GRADE.DiscussionThis study is a review of randomized controlled studies to analyze the efficacy of bladder training in improving the symptoms of adults with overactive bladder syndrome. The study design of randomized controlled trials for a higher level of scientific evidence was chosen. The aim is to obtain results that allow further studies and evidence that this intervention generates beneficial effects in the sample studied.Trial registrationSystematic review registrationPROSPERO CRD42022301522.