bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fmn2 regulates growth cone motility by mediating a molecular clutch to generate traction forces
Authors: Ghate Ketakee , Mutalik Sampada P. , Sthanam Lakshmi Kavitha , Sen Shamik , Ghose Aurnab 
Published: February 2020

ABSTRACTGrowth cone - mediated axonal outgrowth and accurate synaptic targeting are central to brain morphogenesis. Translocation of the growth cone necessitates mechanochemical regulation of cell - extracellular matrix interactions and the generation of propulsive traction forces onto the growth environment. However, the molecular mechanisms subserving force generation by growth cones remain poorly characterized. The formin family member, Fmn2, has been identified earlier as a regulator of growth cone motility. Here, we explore the mechanisms underlying Fmn2 function in the growth cone. Evaluation of multiple components of the adhesion complexes suggests that Fmn2 regulates point contact stability. Analysis of F-actin retrograde flow reveals that Fmn2 functions as a clutch molecule and mediates the coupling of the actin cytoskeleton to the growth substrate, via point contact adhesion complexes. Using traction force microscopy, we show that the Fmn2-mediated clutch function is necessary for the generation of traction stresses by neurons. Our findings suggest that Fmn2, a protein associated with neurodevelopmental and neurodegenerative disorders, is a key regulator of a molecular clutch activity and consequently motility of neuronal growth cones.
R/UAStools::plotshpcreate: Create Multi-Polygon Shapefiles for Extraction of Research Plot Scale Agriculture Remote Sensing Data
Authors: Anderson Steven L. , Murray Seth C. 
Published: February 2020

AbstractAgricultural researchers are embracing remote sensing tools to phenotype and monitor agriculture crops. Specifically, large quantities of data are now being collected on small plot research studies using Unoccupied Aerial Systems (UAS, aka drones), ground systems, or other technologies but, data processing and analysis lags behind. One major contributor to current data processing bottlenecks has been the lack of publicly available software tools tailored towards remote sensing of small plots, and usability for researchers inexperienced in remote sensing. To address these needs we created plot shapefile maker (R/UAS::plotshpcreate), an open source R function which rapidly creates ESRI polygon shapefiles to the desired dimensions of individual agriculture research plots areas of interest and associates plot specific information. Plotshpcreate was developed to utilize inputs containing experimental design, field orientation, and plot dimensions for easily creating a multi-polygon shapefile of an entire small plot experiment. Output shapefiles are based on the user inputs geolocation of the front left corner of the research field ensuring accurate overlay of polygons often without manual user adjustment. The output shapefile is useful in GIS software to extract plot level data tracing back to the unique IDs of the experimental plots. Plotshpcreate is available on GitHub (https://github.com/andersst91/UAStools).
A Novel Method for the Estimation of a Dynamic Effective Reproduction Number (Dynamic-R) in the CoViD-19 Outbreak
Authors: Chong Yi Chen 
Published: February 2020

ABSTRACTThe CoViD-19 outbreak has escalated to a pandemic in the last few weeks, with no signs of stopping. Pharmaceutical solutions based upon virologic studies, at this point, remain inconclusive. In contrast, this paper looks towards epidemiological models during this phase of viral growth, in particular, by providing a responsive, timely model of the R value based on the previous few days’ results.Such an R value, although bearing less statistical precision due to limited sampling, could allow R to become a more effective, responsive standalone measure of infectious transmission. It demonstrates that the R value can be used as a dynamic, time-dependent indicator without the use of curve-fitting, and also estimates the most recent R-value of the CoViD-19 outbreak to be about 4.29, based on the data from the previous 3 days.
Network-based Machine Learning Approach for Structural Domain Identification in Proteins
Authors: Tiwari Anirudh , Parekh Nita 
Published: February 2020

AbstractIn the era of structural genomics, with a large number of protein structures becoming available, identification of domains is an important problem in protein function analysis as it forms the first step in protein classification. Domain identification has been an active area of research for over four decades and a wide range of automated methods have been proposed. In the proposed network-based machine learning approach, NML-DIP, a combination of supervised (SVM) and unsupervised (k-means) machine learning techniques are used for domain identification in proteins. The algorithm proceeds by first representing protein structure as a protein contact network and using topological properties,viz., length, density, and interaction strength (that assesses inter- and intra-domain interactions) as feature vectors in the first SVM to distinguish between single and multi-domain proteins. A second SVM is used to identify the number of domains in multi-domain proteins. Thus, it does not require a prior information of the number of domains. Thek-means algorithm is then used to identify the domain boundaries that are assessed using CATH annotation. The performance of the proposed algorithm is evaluated on four benchmark datasets and compared with four state-of-the-art domain identification methods. The performance of the approach is comparable to other domain identification tools and works well even when the domains are formed with non-contiguous segments. The performance of the program is significantly improved for prior information about the number of domains. The algorithm is available at:https://bit.ly/NML-DIP.
Genomic profiling of cell lines reveals hidden research bias and caveats
Authors: Luo Yongwen , Ju Lingao , Zhang Yi , Xiao Yu , Wang Xinghuan 
Published: February 2020

AbstractCancer cell lines are extremely valuable tools for carcinoma research. Biodiversity of cell lines and continuous random mutation in cell lines during passage, however, might result in phenotypic inconsistency and lead to biased experimental conclusions. Using statistics based on known and inferred protein interaction networks, as well as public research literature database, our study shows that essential driver genotypes of cell lines might have hidden impact on research results. Furthermore, by comprehensive genomic profiling of 8 most common used urothelial cell lines and comparing them to previous publications, we found that regardless of similar short tandem repeat (STR) profile, driver gene loss in cell lines could happen by random mutation. Our results suggest that clinical research using urothelial carcinoma cell lines might be influenced by cell line genotypes which could only be determined by next-generation sequencing. Meanwhile, this study indicates that the conditionally reprogrammed cells (CRCs), which closely resemble original tumor tissue, might represent a better alternative for in vitro research, which may be better used for personalized medicine.
Cellular heterogeneity–adjusted clonal methylation (CHALM) provides better prediction of gene expression
Authors: Xu Jianfeng , Shi Jiejun , Cui Xiaodong , Cui Ya , Li Jingyi Jessica , Goel Ajay , Chen Xi , Su Jianzhong , Issa Jean-Pierre , Li Wei 
Published: February 2020

AbstractPromoter DNA methylation is a well-established mechanism of transcription repression, but its global correlation with gene expression is surprisingly weak. This weak correlation is due in part to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduceCellHeterogeneity–Adjusted cLonalMethylation (CHALM) as a novel methylation quantification method. CHALM better explains the functional consequences of DNA methylation, such as its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method has uniquely detected differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.
Lessons learnt from 288 COVID-19 international cases: importations over time, effect of interventions, underdetection of imported cases
Authors: Pinotti Francesco , Di Domenico Laura , Ortega Ernesto , Mancastroppa Marco , Pullano Giulia , Valdano Eugenio , Boëlle Pierre-Yves , Poletto Chiara , Colizza Vittoria 
Published: February 2020

ABSTRACT288 cases have been confirmed out of China from January 3 to February 13, 2020. We collected and synthesized all available information on these cases from official sources and media. We analyzed importations that were successfully isolated and those leading to onward transmission. We modeled their number over time, in relation to the origin of travel (Hubei province, other Chinese provinces, other countries) and interventions. We characterized importations timeline to assess the rapidity of isolation, and epidemiologically linked clusters to estimate the rate of detection. We found a rapid exponential growth of importations from Hubei, combined with a slower growth from the other areas. We predicted a rebound of importations from South East Asia in the upcoming weeks. Time from travel to detection has considerably decreased since the first importation, however 6 cases out of 10 were estimated to go undetected. Countries outside China should be prepared for the possible emergence of several undetected clusters of chains of local transmissions.
Wald’s martingale and the Moran process
Authors: Monk Travis , van Schaik André 
Published: February 2020

AbstractMany models of evolution are stochastic processes, where some quantity of interest fluctuates randomly in time. One classic example is the Moran birth-death process, where that quantity is the number of mutants in a population. In such processes we are often interested in their absorption (i.e. fixation) probabilities, and the conditional distributions of absorption time. Those conditional time distributions can be very difficult to calculate, even for relatively simple processes like the Moran birth-death model. Instead of considering the time to absorption, we consider a closely-related quantity: the number of mutant population size changes before absorption. We use Wald’s martingale to obtain the conditional characteristic functions of that quantity in the Moran process. Our expressions are novel, analytical, and exact. The parameter dependence of the characteristic functions is explicit, so it is easy to explore their properties in parameter space. We also use them to approximate the conditional characteristic functions of absorption time. We state the conditions under which that approximation is particularly accurate. Martingales are an elegant framework to solve principal problems of evolutionary stochastic processes. They do not require us to evaluate recursion relations, so we can quickly and tractably obtain absorption probabilities and times of evolutionary stochastic processes.Author summaryThe Moran process is a probabilistic birth-death model of evolution. A mutant is introduced to an indigenous population, and we randomly choose organisms to live or die on subsequent time steps. Our goals are to calculate the probabilities that the mutant eventually dominates the population or goes extinct, and the distribution of time it requires to do so. The conditional distributions of time are difficult to obtain for the Moran process, so we consider a slightly different but related problem. We instead calculate the conditional distributions of the number of times that the mutant population size changes before it dominates the population or goes extinct. We use a martingale identified by Abraham Wald to obtain elegant and exact expressions for those distributions. We then use them to approximate conditional time distributions, and we show when that approximation is accurate. Our analysis outlines the basic concepts martingales and demonstrates why they are a formidable tool for studying probabilistic evolutionary models such as the Moran process.
shRNA Glut-1 inhibits cell viability, apoptosis and migration of laryngeal carcinoma HEp-2 cells through regulating Beclin-1-mediated autophagy
Authors: Wang Wen-Dong , Zhu Jin-Long , Zhou Shui-Hong , Fan Jun , Bao Yang-Yang 
Published: February 2020

AbstractObjectiveGlut-1 is a key regulator in the process of glucose uptake. Previous studies have shown that Glut-1 affects autophagy. However, it is unclear whether there is a correlation between Glut-1 and autophagy in the progression of laryngeal carcinoma. This study was performed to investigate the role of Glut-1 in the development of laryngeal carcinoma.MethodsA stable HEp-2 cell model was constructed by Glut-1 and Beclin-1 shRNA lentiviral infection. The autophagosome was measured by transmission electron microscopy. Protein levels of LC3, ATG5, CyclinD1, Bcl-2, Caspase-3, and c-Myc were determined by Western blotting. CCK8 assay and Transwell assays were used to determine cell viability and migration rate of HEp-2 cells, respectively. Flow cytometry was performed to analyze the rate of apoptosis. Immunofluorescence was performed to determine the expression distribution of LC3.ResultsGlut-1 knockdown significantly promoted autophagosome formation by upregulating the ratio of LC3-II/LC3-I as well as the role of rapamycin (RAP) and Beclin-1 overexpression on autophagy flux in HEp-2 cells. Glut-1 inhibition also reduced the viability of HEp-2 cells followed by the decreases in expression of cyclinD1 and c-Myc. In addition, Glut-1 depletion increased the number of apoptotic HEp-2 cells accompanied by activation of caspase-3 and downregulation of Bcl-2. Glut-1 knockdown also reduced the migration rate of HEp-2 cells by promoting the expression of N-cadherin and inhibiting the expression of E-cadherin. Beclin-1 consumption significantly reversed Gult-1 knockdown-mediated autophagy activation, resulting in promotion of both proliferation and migration and inhibition of apoptosis.ConclusionsGlut-1 knockdown-induced autophagy inhibits the proliferation and migration of HEp-2 cells, and promotes apoptosis of HEp-2 cells partly by regulating autophagy.
Marmoset monkeys (Callithrix jacchus) develop eosinophilic airway inflammation after house dust mite exposure
Authors: Dahlmann F , Curths C , Wichmann J , Delgado S Jimenez , Twisterling E , Kap YS , van Driel N , Hart BA’t , Knauf Y , Becker T , Dunker S , Windt H , Bleyer M , Kaup FJ , Sewald K , Braun A , Knauf S 
Published: February 2020

ABSTRACTBackgroundExtensive analysis of eosinophilic airway inflammation in human-relevant animal models is required to test novel, human-specific pharmaceuticals. This requires species, which show high genetic homology to humans such as non-human primates. Efficacy assessment of novel human-specific biologicals in eosinophilic airway inflammation is currently performed in the cost-intensive macaque asthma model.ObjectiveThe present study investigated whether marmoset monkeys (Callithrix jacchus), a small-bodied non-human primate species from the New World, develop eosinophilic airway inflammation in response to house dust mite allergen exposure (HDM,Dermatophagoides pteronyssinus).MethodsMarmoset monkeys were sensitized against HDM by subcutaneous (s.c.) injection and subsequent intratracheal (i.t.) HDM aerosol challenges. Airway and systemic immunologic reactions were monitored and sensitivity towards glucocorticoid therapy was assessed. The pulmonary immunologic response was analyzed by repetitive bronchoalveolar lavage (BAL).ResultsBronchoalveolar lavage fluid (BALF) exhibited increased levels of eosinophils, mast cells, and lymphocytes, as well as interleukin (IL)-13 after HDM challenges, compared to negative controls. The systemic immunologic response was assessed in peripheral blood mononuclear cells derived from sensitized animals, which secreted increased IL-13 and IFN-γ upon allergen stimulation in contrast to non-sensitized negative control animals. Although IgE was not detectable, HDM-specific serum IgG was elevated in sensitized animals. Both airway and systemic responses were reduced by treatment with glucocorticoids. However, lung function and pathological analyses did not reveal significant differences between groups.ConclusionIn conclusion, marmoset monkeys developed a mild HDM-induced eosinophilic airway inflammation useful for efficacy testing of novel human-specific biologicals.
A neutrophil-driven inflammatory signature characterizes the blood cell transcriptome fingerprints of Psoriasis and Kawasaki Disease
Authors: Rawat Arun , Rinchai Darawan , Toufiq Mohammed , Marr Alexandra , Kino Tomoshige , Garand Mathieu , Karim Mohammed Yousuf , Sastry Seetharama , Chouchane Aouatef , Chaussabel Damien 
Published: February 2020

ABSTRACTBackgroundTranscriptome profiling approaches have been widely used in the investigation of mechanisms underlying psoriasis pathogenesis. In most instances, changes in transcript abundance have been measured in skin biopsies. Fewer studies have examined changes in the blood samples from patients with psoriasis. While changes in the periphery may be less relevant, the blood cell transcriptome analysis presents the distinct advantage of being amenable to comparison across diseases.MethodsTwo public psoriasis blood transcriptome datasets were reanalyzed and compared against reference datasets encompassing 16 immune states and pathologies, employing a recently established modular repertoire framework.ResultsAlthough perturbations in psoriasis were relatively subtle in comparison to other auto-immune or auto-inflammatory diseases, consistent changes were observed for a signature associated with neutrophil activation/inflammation. This transcriptional signature most resembled that of subjects with Kawasaki disease.ConclusionsThe similarities observed between psoriasis and Kawasaki disease blood transcriptome signatures suggest that immune mechanisms driving the pathogenesis of these diseases may be at least partially shared. This notion is reinforced by case reports describing the development of psoriasis disease in patients with Kawasaki disease. Potential implications for novel therapeutic approaches, including the repurposing of biologic drugs targeting IL17 or its receptor for the treatment of Kawasaki disease are discussed.
Identification of radiation responsive proteins from Spleen and Intestine tissue of mice using Mass Spectrometry approach
Authors: Husain Md. Shabir , Ahmed Faisal , Kumar Ram , Saini Akhilesh K , Shubham Smriti , Shasthry Saggere M , Tariq Salman Mohammad 
Published: February 2020

AbstractPurposeExposure to ionizing radiation (IR) can cause tissue damage, which is difficult to diagnose and treat as no biomarker is available for detection. We aimed to identify proteomic signature of radiation exposure (9.5Gry) in mice and to assess the utility ofPodophyllotoxinextract (PTOX) in preventing radiation injury.Materials and MethodsSpleen and Small intestinal (SI) tissues were taken from control and lethally irradiated mice at different time intervals with or without pre-treatment withPodophyllotoxinextract. Proteins were identified using Mass Spectrometry and matched with Peptide Mass Fingerprinting.ResultsWe found multiple differentially expressed radiation responsive proteins from Spleen and SI tissues in irradiated mice at 24 hours and 30 days in comparison to healthy controls (p<0.05). Differentially expressed proteins like Chromosome transmission fidelity factor ano thath 18 homolog (CTF18) and Rho GTPase-activating protein from spleen and Acta_Mouse protein from SI were identified. These proteins disappeared at 48 hrs. after IR, but re-appeared after 13 days and fully recovered at 30 days inPodophyllotoxintreated group.ConclusionsSuch proteins may be useful in early detection of radiation exposure. Pre-treatment withPodophyllotoxinleads to recovery of the disappeared proteins and improved survival following exposure to irradiation.
TRIBE editing reveals specific mRNA targets of eIF4E-BP inDrosophilaand in mammals
Authors: Jin Hua , Na Daxiang , Rahman Reazur , Xu Weijin , Fieldsend Allegra , Song Wei , Liu Shaobo , Li Chong , Rosbash Michael 
Published: February 2020

Abstract4E-BP (eIF4E-BP) represses translation initiation by binding to the 5’cap-binding protein eIF4E and inhibiting its activity. Although 4E-BP has been shown to be important in growth control, stress response, cancer, neuronal activity and mammalian circadian rhythms, it is not understood how it preferentially represses a subset of mRNAs. We successfully used hyperTRIBE (Targets of RNA-binding proteins identified by editing) to identify in vivo 4E-BP mRNA targets in bothDrosophilaand mammals under conditions known to activate 4E-BP. The protein associates with specific mRNAs, and ribosome profiling data show that mTOR inhibition changes the translational efficiency of 4E-BP TRIBE targets compared to non-targets. In both systems, these targets have specific motifs and are enriched in translation-related pathways, which correlate well with the known activity of 4E-BP and suggest that it modulates the binding specificity of eIF4E and contributes to mTOR translational specificity.
Altered hematopoietic system and self-tolerance in Bardet-Biedl Syndrome
Authors: Tsyklauri Oksana , Niederlova Veronika , Forsythe Elizabeth , Drobek Ales , Prasai Avishek , Sparks Kathryn , Trachtulec Zdenek , Beales Philip , Huranova Martina , Stepanek Ondrej 
Published: February 2020

AbstractBardet-Biedl Syndrome (BBS) is a pleiotropic genetic disease caused by dysfunction of primary cilia. The immune system of patients with BBS or another ciliopathy has not been investigated, most likely because hematopoietic cells do not form cilia. However, there are multiple indications that the impairment of the processes typically associated with cilia might influence the hematopoietic compartment and immunity. In this study, we analyzed clinical data of BBS patients as well as a corresponding mouse model of BBS4 deficiency. We uncovered that BBS patients have higher incidence of certain autoimmune diseases. BBS patients and animal models have elevated white blood cell levels and altered red blood cell and platelet compartments. Moreover, we observed that BBS4 deficiency alters the development and homeostasis of B cells in mice. Some of the hematopoietic system alterations were caused by the BBS-induced obesity. Overall, our study reveals a connection between a ciliopathy and the alterations of the immune system and the hematopoietic compartment.