bluuebunny/crossref_metadata_2025_split huggingface dataset:
Method for Active Pandemic Curve Management (MAPCM)
Authors: Odendaal Willem G. 
Published: April 2020

AbstractThe COVID-19 pandemic of 2020 prompted stringent mitigation measures to “flatten the curve” quickly leading to an asphyxiated US economy as a national side effect. There are severe drawbacks to this strategy. The resulting flattened curve remains exponential and always under utilizes available healthcare capacity with a chance of still overburdening it. Moreover, while a mitigation strategy involving isolation and containment can scale down infections, it not only prolongs the outbreak significantly, but also leaves a susceptible population in its wake that’s ripe for a secondary outbreak. Since economic activity is inversely proportional to mitigation, curtailing the outbreak with sustained mitigation can stifle the economy severely with disastrous repercussions. Full mitigation for the duration of an outbreak is therefore unsustainable and, overall, a poor solution with potentially catastrophic consequences that could’ve been avoided. A new strategy, coined a “Method for Active Pandemic Curve Management”, or MAPCM, presented herein can shape the outbreak curve in a controlled manner for optimal utilization of healthcare resources during the pandemic, while drastically shortening the outbreak duration compared to mitigation by itself without trading off lives. This method allows mitigation measures to be relaxed gradually from day one, which enables economic activity to resume gradually from the onset of a pandemic. Since outbreak curves (such as hospitalizations) can be programmed using this method, they can also be shaped to accommodate changing needs during the outbreak; and to build herd immunity without the damaging side effects. The method can also be used to ease out of containment. MAPCM is a method and not a model. It is compatible with any appropriate outbreak model; and herein it is illustrated in examples using a hybrid logistic model.
A novel culture-independent method to search unknown dominant bacterial groups and its application to microbial analysis of membrane bioreactors
Authors: Watanabe Katsuji , Horinishi Naoto 
Published: April 2020

ABSTRACTAs we could not get numerical information for unknown unculturable microorganisms through conventional culture-independent analysis methods such as next-generation sequencing, or real time PCR, we developed an original culture-independent method, and searched the numerically dominant bacteria in three industrial membrane bioreactors for livestock farms.AlthoughActinobacteriawas the numerically dominant phylum (9.3×105MPN/mL) on 6/August/2014 in the MBR of A farm, when a bacteria with the same genotype toArthrobactersp. (AF197047; 4.3×105MPN/mL), and those similar toBurkholderia sp. (AB299593; 4.3×105MPN/mL) were the numerically dominant, after about 13 months (24/October/2015) a number of theArthrobactergenotype increased to 930×105MPN (230 times) and become dominant, and those similar to theMicrobacteriumsp. (AM403628) increased to 92×105MPN, while that of theBurkholderia genotype disappeared. In the other MBR of B farm, bacteria having a similar genotype toEnshifersp. (AB195268, CP000738), orShinorhizobiumsp. (AF227755, AB195268), orMesorhizobiumsp. (BA000012, Mso.tians29), orAgrobacterium vitis(D12795) was dominant on 18/August/2015 (24×105MPN) and 30/August/2015 (15.5×105MPN). In the other MBR of C farm (9/October/2015), bacteria having a similar genotype to unculturedBetaproteobacteria(AY921864) was dominant (430×105MPN), followed by uncultured bacterium (74×105MPN ; AM268745), andMycobacteriaceae(AB298730), orPropionibacteriaceae(AB298731) (7.4 ×105MPN). There was no common bacterial groups among tested three MBRs. Present results indicated that different kinds of homogeneous bacteria were numerically dominant in the three tested membrane bioreactors, where their numbers and ratios were varied with the duration of the driving periods.IMPORTANCEAlthough the conventional molecular-based culture independent methods have been used in place of traditional culture-based methods for microbiological research and expanded information of unculturable low-abundance bacterial groups, not all of them were always highly active in the environment and it was difficult to search for microorganisms among them which were highly active and play an important role in the environment. As numerical data of each bacteria might become an important index to know their activity in environment, we had created a novel culture-independent enumeration method for numerically dominant unidentified bacteria. Through the method, we found that different kinds of homogeneous bacteria were numerically dominant in the three tested membrane bioreactors, whose numbers were high enough to affect the performance of the reactor as a single strain. The method was found useful to specify and trace unknown numerically dominant bacterial groups in a culture independent manner.
Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions
Authors: Farkas Carlos , Fuentes-Villalobos Francisco , Garrido José Luis , Haigh Jody J , Barría María Inés 
Published: April 2020

AbstractHere we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.
Proteogenomics analysis of non-coding region encoded peptides in normal tissues and five cancer types
Authors: Xiang Rong , Ma Leyao , Yang Mingyu , Zheng Zetian , Chen Xiaofang , Jia Fujian , Xie Fanfan , Li Fuqiang , Wu Kui , Zhu Yafeng 
Published: April 2020

AbstractPrevious proteogenomics studies have identified peptides encoded by non-coding sequences such as pseudogenes and long non-coding RNAs (lncRNAs) in healthy human tissues as well as in cancers. However, these studies are either limited to analyze only healthy or cancerous tissues, lacking direct comparison between them. In this study, we used an established proteogenomics analysis workflow to analyze proteomics data from 926 cancer samples of five cancer types and 31 different healthy human tissues. We observed the protein level expression of pseudogenes can be classified as ubiquitous or lineage expression. The ubiquitously translated pseudogenes are homologous to house-keeping genes. Our results suggest there is common mechanism underlying the translation of pseudogenes in both normal and tumors. Moreover, we discovered several translated non-coding genes such asDGCR5andRHOXF1P3that were up-regulated in tumors compared to normal. These translated pseudogenes imply the biological function of pseudogenes extends to protein level yet to be studied. Further, from the non-coding region encoded peptides specifically detected in tumors we have predicted a large number of potential neoantigens which can be developed as cancer vaccine.
In vivovisual screen for dopaminergicRab ↔ LRRK2-G2019Sinteractions inDrosophiladiscriminatesRab10fromRab3
Authors: Petridi Stavroula , Middleton C. Adam , Ugbode Chris , Fellgett Alison , Covill Laura , Elliott Christopher J. H. 
Published: April 2020

AbstractLRRK2 mutations cause Parkinson’s, but the molecular link from increased kinase activity to pathological neurodegeneration remains undetermined. Previousin vitroassays indicate that LRRK2 substrates include at least 8 Rab GTPases. We have now examined this hypothesisin vivoin a functional, electroretinogram screen, expressing eachRabwith/withoutLRRK2-G2019Sin selectedDrosophiladopaminergic neurons. Our screen discriminated Rab10 from Rab3. The strongest Rab/LRRK2-G2019S interaction is with Rab10; the weakest with Rab3. Rab10 is expressed in a different set of dopaminergic neurons from Rab3. Thus, anatomical and physiological patterns of Rab10 are related. We conclude that Rab10 is a valid substrate of LRRK2 in dopaminergic neuronsin vivo. We propose that variations inRabexpression contribute to differences in the rate of neurodegeneration recorded in different dopaminergic nuclei in Parkinson’s.
Repurposing a digital kitchen scale for neuroscience research: a complete hardware and software cookbook for PASTA
Authors: Virag D , Homolak J , Kodvanj I , Babic Perhoc A , Knezovic A , Osmanovic Barilar J , Salkovic-Petrisic M 
Published: April 2020

AbstractWidely available low-cost electronics encourage the development of open-source tools for neuroscientific research. In recent years, many neuroscientists recognized the open science movement for its potential to stimulate and encourage science that is less focused on money, and more on robustness, validity, questioning and understanding. Here, we wanted to contribute to this global community by creating a research platform based on a common digital kitchen scale. This everyday ordinary kitchen tool is sometimes used in neuroscience research in various ways; however, its use is limited by sampling rate and inability to store and analyze data. To tackle this problem we developed a Platform for Auditory STArtle or PASTA. This robust and simple platform enables users to obtain data from kitchen scale load cells at a high sampling rate, store it and analyze it. Here, we used it to analyze acoustic startle and prepulse inhibition sensorimotor gating in rats treated intracerebroventricularly with streptozotocin, but the system can be easily modified and upgraded for other purposes. In accordance with open science principles, we shared complete hardware design with instructions. Furthermore, we also disclose our software codes written for PASTA data acquisition (C++, Arduino) and acoustic startle experimental protocol (Python) and analysis (R-based Awesome Toolbox for PASTA, ratPASTA R package). To further encourage the development of our PASTA platform we demonstrate its sensitivity by using PASTA-gathered data to extract breathing patterns during rat freezing behavior in our experimental protocol.
STAT1 dissociates adipose tissue inflammation from insulin sensitivity in obesity
Authors: Cox Aaron R. , Chernis Natasha , Bader David A. , Saha Pradip K , Masschelin Peter M. , Felix Jessica , Lian Zeqin , Putluri Vasanta , Rajapakshe Kimal , Kim Kang Ho , Villareal Dennis T. , Armamento-Villareal Reina , Wu Huaizhu , Coarfa Cristian , Putluri Nagireddy , Hartig Sean M 
Published: April 2020

AbstractObesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes mellitus (T2DM). However, the causal relationship of these events remains unclear. The established dominance of signal transducer and activator of transcription 1 (STAT1) function in the immune response suggests an obligate link between inflammation and the co-morbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1 fKO) enhanced mitochondrial function and accelerated TCA cycle flux coupled with subcutaneous WAT hyperplasia. STAT1 fKO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFNγ) activity enhanced insulin sensitivity in diet-induced obesity. Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.
Perfusion bioreactor culture of adipose-derived stromal cells on decellularized adipose tissue scaffolds enhancesin vivoregeneration
Authors: Y. Han Tim Tian , E. Flynn Lauren 
Published: April 2020

AbstractAdipose tissue engineering holds promise to address the unmet need in plastic and reconstructive surgery for strategies that promote the stable and predictable regeneration of adipose tissue for volume augmentation applications. Previous studies have demonstrated that decellularized adipose tissue (DAT) scaffolds can provide a pro-adipogenic microenvironment, and that seeding with adipose-derived stromal cells (ASCs) can enhancein vivoangiogenesis and adipogenesis within DAT implants. Recognizing that bioreactor systems can promote cell expansion and infiltration on tissue-engineered scaffolds, this study evaluated the effects of culturing human ASCs on DAT scaffolds within a perfusion bioreactor. Using this system, the impact of both shear stress stimulation and hypoxic preconditioning were exploredin vitroandin vivo. Initial studies compared the effects of 14 days of culture within the perfusion bioreactor under 2% O2or ~20% O2on human ASC expansion and hypoxia inducible factor 1 alpha (HIF-1α) expressionin vitrorelative to static cultured controls. The findings indicated that culturing within the bioreactor under 2% O2significantly increased ASC proliferation on the DAT, with a higher cell density observed in the scaffold periphery. HIF-1α expression was significantly higher when the scaffolds were cultured under 2% O2. Subsequent characterization in a subcutaneous implant model in athymic nude mice revealed thatin vivoangiogenesis and adipogenesis were markedly enhanced when the ASCs were cultured on the DAT within the perfusion bioreactor under 2% O2for 14 days prior to implantation relative to the other culture conditions, as well as additional freshly-seeded and unseeded DAT control groups. Overall, dynamic culture within the perfusion bioreactor system under hypoxia represents a promising approach for preconditioning ASCs on DAT scaffolds to enhance their capacity to stimulate blood vessel formation and infiltration, as well as host-derived adipose tissue regeneration.
Heme-Sensing Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics
Authors: Smith Kaitlyn H. , Budhraja Amit , Lynch John , Roberts Kathryn , Panetta John C. , Connelly Jon P. , Turnis Meghan E. , Pruett-Miller Shondra M. , Schuetz John D. , Mullighan Charles G. , Opferman Joseph T. 
Published: April 2020

AbstractAnti-apoptoticMCL1is one of the most frequently amplified genes in human cancers and elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation ofEif2ak1, which encodes HRI, blocks MCL-1 repression in response to DHA treatment and represses the synergistic killing of DHA and BH3-mimetics compared to wild-type leukemia. Furthermore, BTdCPU, a small-molecule activator of HRI, similarly triggers MCL-1 repression and synergizes with BH3-mimetics in mouse and human leukemia including both Ph+and Ph-like B-ALL. Lastly, combinatorial treatment of leukemia bearing mice with both BTdCPU and a BH3-mimetic extended survival and repressed MCL-1in vivo. These findings reveal for the first time that the HRI-dependent cellular heme-sensing pathway can modulate apoptosis in leukemic cells by repressing MCL-1 and increasing their responsiveness to BH3-mimetics. This signaling pathway could represent a generalizable mechanism for repressing MCL-1 expression in malignant cells and sensitizing them to available therapeutics.
A Computational Approach to Design Potential siRNA Molecules as a Prospective Tool for Silencing Nucleocapsid Phosphoprotein and Surface Glycoprotein Gene of SARS-CoV-2
Authors: Chowdhury Umar Faruq , Shohan Mohammad Umer Sharif , Hoque Kazi Injamamul , Beg Mirza Ashikul , Siam Mohammad Kawsar Sharif , Moni Mohammad Ali 
Published: April 2020

ABSTRACTAn outbreak, caused by a RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a magnitude which is daunting to all public health institutions in the absence of specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections by suppressing viral gene expression through hybridization and neutralization of target complementary mRNA. So, in this study, the power of RNA interference technology was harnessed to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of folding, free energy of binding, melting temperature and efficacy prediction process 8 siRNA molecules were selected which are proposed to exerts the best action. These predicted siRNAs should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in the response against SARS-CoV-2
Holobiont Evolution: Population Theory for the Hologenome
Authors: Roughgarden Joan 
Published: April 2020

AbstractThis article develops mathematical theory for the population dynamics of microbiomes with their hosts and for holobiont evolution caused by holobiont selection. The objective is to account for the formation of microbiome-host integration.Microbial population-dynamic parameters must mesh with the host’s for coexistence.A horizontally transmitted microbiome is a genetic system with “collective inheritance”. The microbial source pool in the environment corresponds to the gamete pool for nuclear genes. Poisson sampling of the microbial source pool corresponds to binomial sampling of the gamete pool. However, holobiont selection on the microbiome does not lead to a counterpart of the Hardy-Weinberg Law nor to directional selection that always fixes microbial genes conferring the highest holobiont fitness.A microbe might strike an optimal fitness balance between lowering its within-host fitness while increasing holobiont fitness. Such microbes are replaced by otherwise identical microbes that contribute nothing to holobiont fitness. This replacement can be reversed by hosts that initiate immune responses to non-helpful microbes. This discrimination leads to microbial species sorting. Host-orchestrated species sorting (HOSS) followed by microbial competition, rather than co-evolution or multi-level selection, is predicted to be the cause of microbiome-host integration.
Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers
Authors: El Alam Molly B. , Sims Travis T. , Kouzy Ramez , Biegert Greyson W. G. , Abi Jaoude Joseph , Karpinets Tatiana V. , Yoshida-Court Kyoko , Wu Xiaogang , Delgado Medrano Andrea Y. , Mezzari Melissa P. , Ajami Nadim J. , Solley Travis , Ahmed-Kaddar Mustapha , Lin Lilie L. , Ramondetta Lois , Jazaeri Amir , Jhingran Anuja , Eifel Patricia J. , Schmeler Kathleen M. , Wargo Jennifer , Klopp Ann H. , Colbert Lauren E. 
Published: April 2020

ABSTRACTBackgroundA diverse and abundant gut microbiome can improve cancer patients’ treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT.Materials and MethodsRectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size.ResultsGut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; allP<0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species.ConclusionAfter CRT, the gut microbiome’s diversity tends to return to baseline levels, but its structure and composition remain significantly altered. These changes should be considered when designing studies to analyze the gut microbiome as a predictive or prognostic biomarker in patients who receive pelvic CRT for gynecologic cancers.
Sensitivity to Monoclonal Antibody 447-52D and an Open Env Trimer Conformation Correlate Poorly with Inhibition of HIV-1 Infectivity by SERINC5
Authors: Angerstein Aaron O. , Stoneham Charlotte A. , Ramirez Peter W. , Guatelli John C. , Vollbrecht Thomas 
Published: April 2020

AbstractThe host protein SERINC5 inhibits the infectivity of HIV-1 virions in an Env-dependent manner and is counteracted by Nef. The conformation of the Env trimer reportedly correlates with sensitivity to SERINC5. Here, we tested the hypothesis that the “open” conformation of the Env trimer revealed by sensitivity to the V3-loop specific antibody 447-52D directly correlates with sensitivity to SERINC5. Of five Envs tested, SF162 was the most sensitive to neutralization by 447-52D, but it was not the most sensitive to SERINC5; instead the Env of LAI was substantially more sensitive to SERINC5 than all the other Envs. Mutational opening of the trimer by substitution of two tyrosines that mediate interaction between the V2 and V3 loops sensitized the Envs of JRFL and LAI to 447-52D as previously reported, but only BaL was sensitized to SERINC5. These data suggest that trimer “openness” is not sufficient for sensitivity to SERINC5.