bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDRP: real-time phenology and climatic suitability modeling of invasive insects
Authors: Barker Brittany S. , Coop Leonard , Wepprich Tyson , Grevstad Fritzi , Cook Gericke 
Published: May 2020

AbstractRapidly detecting and responding to new invasive species and the spread of those that are already established is essential for reducing their potential threat to food production, the economy, and the environment. We describe a new multi-species spatial modeling platform that integrates mapping of phenology and climatic suitability in real-time to provide timely and comprehensive guidance for stakeholders needing to know both where and when invasive insect species could potentially invade the conterminous United States. The Degree-Days, Risk, and Phenological event mapping (DDRP) platform serves as an open-source and relatively easy-to-parameterize decision support tool to help detect new invasive threats, schedule monitoring and management actions, optimize biological control, and predict potential impacts on agricultural production. DDRP uses a process-based modeling approach in which degree-days and temperature stress are calculated daily and accumulate over time to model phenology and climatic suitability, respectively. Products include predictions of the number of completed generations, life stages present, dates of phenological events, and climatically suitable areas based on two levels of climate stress. Species parameter values can be derived from laboratory and field studies, and from published and newly fitted CLIMEX models. DDRP is written entirely in R, making it flexible and extensible, and capitalizes on multiple R packages to generate gridded and graphical outputs. We illustrate the DDRP modeling platform and the process of model parameterization using two invasive insect species as example threats to United States agriculture: the light brown apple moth,Epiphyas postvittana, and the small tomato borer,Neoleucinodes elegantalis.We then discuss example applications of DDRP as a decision support tool, review its potential limitations and sources of model error, and outline some ideas for future improvements to the platform.
PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection
Authors: Hölzer Martin , Marz Manja 
Published: May 2020

ABSTRACTSummaryPoSeiDon is an easy-to-use pipeline that helps researchers to find recombination events and sites under positive selection in protein-coding sequences. By entering homologous sequences, PoSeiDon builds an alignment, estimates a best-fitting substitution model, and performs a recombination analysis followed by the construction of all corresponding phylogenies. Finally, significantly positive selected sites are detected according to different models for the full alignment and possible recombination fragments. The results of PoSeiDon are summarized in a user-friendly HTML page providing all intermediate results and the graphical representation of recombination events and positively selected sites.Availability and implementationPoSeiDon is freely available athttps://github.com/hoelzer/poseidon. The pipeline is implemented in Nextflow with Docker support and processes the output of various tools.Contacthoelzer.martin@gmail.com
Transcranial Focused Ultrasound Neuromodulation of Voluntary Movement-related Cortical Activity in Humans
Authors: Yu Kai , Liu Chang , Niu Xiaodan , He Bin 
Published: May 2020

AbstractTranscranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation tool for safely and reversibly modulating brain circuits. The effectiveness of tFUS on human brain has been demonstrated, but how tFUS influences the human voluntary motor processing in the brain remains unclear. We apply low-intensity tFUS to modulate the movement-related cortical potential (MRCP) originating from human subjects practicing a voluntary foot tapping task. 64-channel electroencephalograph (EEG) is recorded concurrently and further used to reconstruct the brain source activity specifically at the primary leg motor cortical area using the electrophysiological source imaging (ESI). The ESI illustrates the ultrasound modulated MRCP source dynamics with high spatiotemporal resolutions. The MRCP source is imaged and its source profile is further evaluated for assessing the tFUS neuromodulatory effects on the voluntary MRCP. Moreover, the effect of ultrasound pulse repetition frequency (UPRF) is further assessed in modulating the MRCP. ESI results show that tFUS significantly increases the MRCP source profile amplitude (MSPA) comparing to a sham ultrasound condition, and further, a high UPRF enhances the MSPA more than a low UPRF. This work provides the first evidence of tFUS enhancing the human voluntary movement-related cortical activity through excitatory modulation.
Werner syndrome protein (WRN) regulates cell proliferation and the human papillomavirus 16 life cycle during epithelial differentiation
Authors: James Claire D. , Das Dipon , Morgan Ethan L. , Otoa Raymonde , Macdonald Andrew , Morgan Iain M. 
Published: May 2020

AbstractHuman papillomaviruses recruit a host of DNA damage response factors to their viral genome to facilitate homologous recombination replication in association with the viral replication factors E1 and E2. We previously demonstrated that SIRT1 deacetylation of WRN promotes recruitment of WRN to E1-E2 replicating DNA, and that WRN regulates both the levels and fidelity of E1-E2 replication. The deacetylation of WRN by SIRT1 results in an active protein able to complex with replicating DNA, but a protein that is less stable. Here we demonstrate an inverse correlation between SIRT1 and WRN in CIN cervical lesions when compared with normal control tissue, supporting our model of SIRT1 deacetylation destabilizing WRN protein. We CRISPR/Cas9 edited N/Tert-1 and N/Tert-1+HPV16 cells to knock out WRN protein expression and subjected the cells to organotypic raft cultures. In N/Tert-1 cells without WRN expression there was enhanced basal cell proliferation, DNA damage and thickening of the differentiated epithelium. In N/Tert-1+HPV16 cells, there was enhanced basal cell proliferation, increased DNA damage throughout the epithelium and increased viral DNA replication. Overall, the results demonstrate that the expression of WRN is required to control the proliferation of N/Tert-1 cells and controls the HPV16 life cycle in these cells. This complements our previous data demonstrating that WRN controls the levels and fidelity of HPV16 E1-E2 DNA replication. The results describe a new role for WRN, a tumor suppressor, in controlling keratinocyte differentiation and the HPV16 life cycle.ImportanceHPV16 is the major human viral carcinogen, responsible for around 3-4% of all cancers worldwide. Our understanding of how the viral replication machinery interacts with host factors to control/activate the DNA damage response to promote the viral life cycle remains incomplete. Recently, we demonstrated a SIRT1-WRN axis that controls HPV16 replication and here we demonstrate that this axis persists in clinical cervical lesions induced by HPV16. Here we describe the effects of WRN depletion on cellular differentiation with and without HPV16; WRN depletion results in enhanced proliferation and DNA damage irrespective of HPV16 status. Also, WRN is a restriction factor for the viral life cycle as replication is disrupted in the absence of WRN. Future studies will focus on enhancing our understanding of how WRN regulates viral replication. Our goal is to ultimately identify cellular factors essential for HPV16 replication that can be targeted for therapeutic gain.
Reproduction ratio and growth rates: measures for an unfolding pandemic
Authors: Aguiar Maíra , Van-Dierdonck Joseba Bidaurrazaga , Stollenwerk Nico 
Published: May 2020

AbstractThe initial exponential growth rate of an epidemic is an important measure that follows directly from data at hand, commonly used to infer the basic reproduction number. As the growth rates λ(t) of tested positive COVID-19 cases have crossed the threshold in many countries, with negative numbers as surrogate for disease transmission deceleration, lockdowns lifting are linked to the behavior of the momentary reproduction numbers r(t), often called R0. Important to note that this concept alone can be easily misinterpreted as it is bound to many internal assumptions of the underlying model and significantly affected by the assumed recovery period. Here we present our experience, as part of the Basque Country Modeling Task Force (BMTF), in monitoring the development of the COVID-19 epidemic, by considering not only the behaviour of r(t) estimated for the new tested positive cases - significantly affected by the increased testing capacities, but also the momentary growth rates for hospitalizations, ICU admissions, deceased and recovered cases, in assisting the Basque Health Managers and the Basque Government during the lockdown lifting measures. Two different data sets, collected and then refined during the COVID-19 responses, are used as an exercise to estimate the momentary growth rates and reproducetion numbers over time in the Basque Country, and the implications of using those concepts to make decisions about easing lockdown and relaxing social distancing measures are discussed. These results are potentially helpful for task forces around the globe which are now struggling to provide real scientific advice for health managers and governments while the lockdown measures are relaxed.
Mitochondrial D-loop sequence variation and maternal lineage in the endangered Cleveland Bay horse
Authors: Dell A.C. , Curry M.C. , Yarnell K.M. , Starbuck G.R. , Wilson P. B. 
Published: May 2020

AbstractGenetic diversity and maternal ancestry line relationships amongst a sample of 96 Cleveland Bay horses were investigated using a 479bp length of mitochondrial D-loop sequence. The analysis yielded at total of 11 haplotypes with 27 variable positions, all of which have been described in previous equine mitochondrial DNA d-loop studies. Four main haplotype clusters were present in the Cleveland Bay breed describing 89% of the total sample. This suggests that only four principal maternal ancestry lines exist in the present-day global Cleveland Bay population. Comparison of these sequences with other domestic horse haplotypes shows a close association of the Cleveland Bay horse with Northern European (Clade C), Iberian (Clade A) and North African (Clade B) horse breeds. This indicates that the Cleveland Bay horse may not have evolved exclusively from the now extinct Chapman horse, as previous work as suggested. The Cleveland Bay horse remains one of only fivedomestic horse breeds classified as Critical on the Rare Breeds Survival Trust (UK) Watchlist and our results provide important information on the origins of this breed and represent a valuable tool for conservation purposes.
Abl kinase deficiency promotes AKT pathway activation and prostate cancer progression and metastasis
Authors: Marchal Melissa A , Moose Devon L , Varzavand Afshin , Taylor Destiney , Brown James A , Henry Michael D , Stipp Christopher S 
Published: May 2020

AbstractAbl family kinases function as proto-oncogenes in various leukemias, and pro-tumor functions have been discovered for Abl kinases in solid tumors as well. However, a growing body of evidence indicates that Abl kinases can function to suppress tumor cell proliferation, motility, andin vivotumor growth in some settings. To investigate the role of Abl kinases in prostate cancer, we generated Abl-deficient cells in a pre-clinical model of spontaneously metastatic, androgen-indifferent prostate cancer. Loss of Abl family kinase expression resulted in a highly aggressive, metastatic phenotypein vivothat was associated with AKT pathway activation, increased growth on 3D collagen matrix, and enhanced cell motilityin vitro. Treatment of Abl kinase-expressing cells with the Abl kinase inhibitor imatinib phenocopied the malignant phenotypes observed in Abl-deficient tumor cells. In addition, inhibiting AKT pathway signaling abolished the increased 3D growth of Abl-deficient cells. Our data reveal that Abl family kinases can function as suppressors of prostate cancer progression and metastasis by restraining AKT signaling, a signaling pathway known to be associated with emergence of metastatic castration-resistant prostate cancer.
PrimPol primase mediates replication traverse of DNA interstrand crosslinks
Authors: González-Acosta Daniel , Blanco-Romero Elena , Mutreja Karun , Llanos Susana , Míguez Samuel , García Fernando , Muñoz Javier , Blanco Luis , Lopes Massimo , Méndez Juan 
Published: May 2020

ABSTRACTInterstrand crosslinks (ICLs) are DNA lesions frequently induced by chemotherapy that interfere with essential processes such as replication and transcription. ICL repair may be initiated by the convergence of two replication forks at the crosslink, which results in a termination-like DNA structure recognized and processed by the Fanconi Anemia (FA) pathway. An alternative possibility to generate a suitable substrate for ICL repair involves “ICL traverse”, a DNA damage tolerance mechanism in which a single fork arriving at the ICL can skip the lesion and restart DNA synthesis from a downstream point. This reaction requires FANCM translocase, the BLM/TOP3A/RMI1-2 (BTR) complex and other factors. Here we report that PrimPol, the second primase-polymerase identified in mammalian cells after Polα/Primase, interacts with BTR and participates in the ICL traverse reaction. A functional complementation assay reveals that the primase activity of PrimPol is required, confirming the need for re-priming events during ICL traverse. Genetic ablation of PRIMPOL strongly impaired this tolerance mechanism, making cells more dependent on fork convergence to initiate ICL repair. PRIMPOL KO cells and mice display hypersensitivity to ICL-inducing drugs, opening the possibility of targeting PrimPol activity to enhance the efficacy of chemotherapy based on DNA crosslinking agents.
A redesigned TetR-aptamer system to control gene expression inPlasmodium falciparum
Authors: Rajaram Krithika , Liu Hans B. , Prigge Sean T. 
Published: May 2020

AbstractOne of the most powerful approaches to understanding gene function involves turning genes on and off at will and measuring the impact at the cellular or organismal level. This particularly applies to the cohort of essential genes where traditional gene knockouts are inviable. InPlasmodium falciparum, conditional control of gene expression has been achieved by using multi-component systems in which individual modules interact with each other to regulate DNA recombination, transcription or posttranscriptional processes. The recently devised TetR-DOZI aptamer system relies on the ligand-regulatable interaction of a protein module with synthetic RNA aptamers to control the translation of a target gene. This technique has been successfully employed to study essential genes inP. falciparumand involves the insertion of several aptamer copies into their 3’ untranslated regions (UTRs) which provide control over mRNA fate. However, aptamer repeats are prone to recombination and one or more copies can be lost from the system, resulting in a loss of control over target gene expression. We rectified this issue by redesigning the aptamer array to minimize recombination while preserving the control elements. As proof of concept, we compared the original and modified arrays for their ability to knock down the levels of a putative essential apicoplast protein (PF3D7_0815700) and demonstrated that the modified array is highly stable and efficient. This redesign will enhance the utility of a tool that is quickly becoming a favored strategy for genetic studies inP. falciparum.ImportanceMalaria elimination efforts have been repeatedly hindered by the evolution and spread of multidrug-resistant strains ofPlasmodium falciparum. The absence of a commercially available vaccine emphasizes the need for a better understanding ofPlasmodiumbiology in order to further translational research. This has been partly facilitated by targeted gene deletion strategies for the functional analysis of parasite genes. However, genes that are essential for parasite replication in erythrocytes are refractory to such methods, and require conditional knockdown or knockout approaches to dissect their function. One such approach is the TetR-DOZI system that employs multiple synthetic aptamers in the untranslated regions of target genes to control their expression in a tetracycline-dependent manner. Maintaining modified parasites with intact aptamer copies has been challenging since these repeats are frequently lost by recombination. By interspacing the aptamers with unique sequences, we created a stable genetic system that remains effective at controlling target gene expression.
Clinical And Analytical Performance Of An Automated Serological Test That Identifies S1/S2 Neutralizing IgG In Covid-19 Patients Semiquantitatively
Authors: Bonelli Fabrizio , Sarasini Antonella , Zierold Claudia , Calleri Mariella , Bonetti Alice , Vismara Chiara , Blocki Frank , Pallavicini Luca , Chinali Alberto , Campisi Daniela , Percivalle Elena , DiNapoli Anna Pia , Perno Carlo Federico , Baldanti Fausto 
Published: May 2020

ABSTRACTBACKGROUNDIn the Covid-19 pandemic, highly selective serological testing is essential to define exposure to SARS-CoV-2 virus. Many tests have been developed, yet with variable speed to first result, and of unknown quality, particularly when considering the prediction of neutralizing capacity.OBJECTIVES/METHODSThe LIAISON®SARS-CoV-2 S1/S2 IgG assay was designed to measure antibodies against the SARS-CoV-2 native S1/S2 proteins in a standardized automated chemiluminescent assay. Clinical and analytical performance of the test were validated in an observational study using residual samples (>1500) with positive or negative Covid-19 diagnosis.RESULTSThe LIAISON®SARS-CoV-2 S1/S2 IgG assay proved highly selective and specific, and offers semiquantitative measures of serum or plasma levels of anti-S1/S2 IgG with neutralizing activity. The diagnostic sensitivity was 91.3% and 95.7% at >5 or ≥15 days from diagnosis respectively, and 100% when assessed against a neutralizing assay. The specificity ranged between 97% and 98.5%. The average imprecision of the assay was <5 % coefficient of variation. Assay performance at 2 different cut-offs was evaluated to optimize predictive values in settings with different % disease prevalence. CONCLUSIONS. The automated LIAISON®SARS-CoV-2 S1/S2 IgG assay brings efficient, sensitive, specific, and precise serological testing to the laboratory, with the capacity to test large amounts of samples per day: first results are available within 35 minutes with a throughput of 170 tests/hour. The test also provides a semiquantitative measure to identify samples with neutralizing antibodies, useful also for a large scale screening of convalescent plasma for safe therapeutic use.IMPORTANCEWith the worldwide advance of the COVID-19 pandemic, efficient, reliable and accessible diagnostic tools are needed to support public health officials and healthcare providers in their efforts to deliver optimal medical care, and articulate sound demographic policy. DiaSorin has developed an automated serology based assay for the measurement of IgG specific to SARS CoV-2 Spike protein, and tested its clinical performance in collaboration with Italian health care professionals who provided access to large numbers of samples from infected and non-infected individuals. The assay delivers excellent sensitivity and specificity, and is able to identify samples with high levels of neutralizing antibodies. This will provide guidance in assessing the true immune status of subjects, as well as meeting the pressing need to screen donors for high titer convalescent sera for subsequent therapeutic and prophylactic use.
Morphologic Classification and Automatic Diagnosis of Bacterial Vaginosis by Deep Neural Networks
Authors: Wang Zhongxiao , Zhang Lei , Zhao Min , Wang Ying , Bai Huihui , Wang Yufeng , Rui Can , Fan Chong , Li Jiao , Li Na , Liu Xinhuan , Wang Zitao , Si Yanyan , Feng Andrea , Li Mingxuan , Zhang Qiongqiong , Yang Zhe , Wang Mengdi , Wu Wei , Cao Yang , Qi Lin , Zeng Xin , Geng Li , An Ruifang , Li Ping , Liu Zhaohui , Qiao Qiao , Zhu Weipei , Mo Weike , Liao Qinping , Xu Wei 
Published: May 2020

AbstractBackgroundBacterial vaginosis (BV) was the most common condition for women’s health caused by the disruption of normal vaginal flora and an overgrowth of certain disease-causing bacteria, affecting 30-50% of women at some time in their lives. Gram stain followed by Nugent scoring (NS) based on bacterial morphotypes under the microscope was long considered golden standard for BV diagnosis. This conventional manual method was often considered labor intensive, time consuming, and variable results from person to person.MethodsWe developed four convolutional neural networks (CNN) models, and evaluated their ability to automatic identify vaginal bacteria and classify Nugent scores from microscope images. All the CNN models were first trained with 23280 microscopic images labeled with Nugent scores from top experts. A separate set of 5815 images were evaluated by the CNN models. The best CNN model was selected to generalize its application on an independent sets of 1082 images collecting from three teaching hospitals. Different hardwares were used to take images in hospitals.ResultsOur model could classify three Nugent Scores from images with high three classification accuracy of 89.3% (with 82.4% sensitivity and 96.6% specificity) on the 5815 test images, which was better diagnostic yield than the top-level technologists and obstetricians in China. The ability of generalization for our model was strong that it obtained 75.1%, which was 6.6% higher than the average of technologists.ConclusionThe CNN model over performed human healthcare practitioners on accuracy, efficiency and stability for BV diagnosis using microscopic image-based Nugent scores. The deep learning model may offer translational application in automating diagnosis of bacterial vaginosis with proper supporting hardware.
S-nitrosylated and non-nitrosylated COX2 has differential expression and distinct subcellular localization in normal and breast cancer tissue
Authors: Jindal Sonali , Pennock Nathan D. , Klug Alex , Narasimhan Jayasri , Calhoun Andrea , Roberts Michelle R. , Tamimi Rulla M. , Eliassen A. Heather , Weinmann Sheila , Borges Virginia F. , Schedin Pepper 
Published: May 2020

AbstractImmunohistochemical staining in breast cancer shows both gain and loss of COX2 expression with disease risk and progression. We investigated four common COX2 antibody clones and found high specificity for purified human COX2 for three clones; however, recognition of COX2 in cell lysates was clone dependent. Biochemical characterization revealed two distinct forms of COX2, with SP21 recognizing an S-nitrosylated form and CX229 and CX294 appearing to recognize the same non-nitrosylated COX2 antigen. We found S-nitrosylated and non-nitrosylated COX2 occupy different subcellular locations in normal and breast cancer tissue, implicating distinct synthetic/trafficking pathways and function. Dual stains of ~2000 breast cancer cases show early onset breast cancer has increased expression of both forms of COX2 compared to postmenopausal cases. Our results highlight the strengths of using multiple, highly characterized antibody clones for COX2 immunohistochemical studies and raise the prospect that S-nitrosylation of COX2 may play a role in breast cancer biology.