bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging Back Clinics—a Geriatric Syndrome Approach to Treating Chronic Low Back Pain in Older Adults: Results of a Preliminary Randomized Controlled Trial
Authors: Weiner Debra K , Gentili Angela , Rossi Michelle , Coffey-Vega Katherine , Rodriguez Keri L , Hruska Kristina L , Hausmann Leslie , Perera Subashan 
Published: July 2019

Abstract

Objective
Treating chronic low back pain (CLBP) with spine-focused interventions is common, potentially dangerous, and often ineffective. This preliminary trial tests the feasibility and efficacy of caring for CLBP in older adults as a geriatric syndrome in Aging Back Clinics (ABC).

Design
Randomized controlled trial.

Setting
Outpatient clinics of two VA Medical Centers.

Subjects
Fifty-five English-speaking veterans aged 60–89 with CLBP and no red flags for serious underlying illness, prior back surgery, dementia, impaired communication, or uncontrolled psychiatric illness.

Methods
Participants were randomized to ABC care or usual care (UC) and followed for six months. ABC care included 1) a structured history and physical examination to identify pain contributors, 2) structured participant education, 3) collaborative decision-making, and 4) care guided by condition-specific algorithms. Primary outcomes were low back pain severity (0–10 current and seven-day average/worst pain) and pain-related disability (Roland Morris). Secondary outcomes included the SF-12 and health care utilization.

Results
ABC participants experienced significantly greater reduction in seven-day average (–1.22 points, P = 0.023) and worst pain (–1.70 points, P = 0.003) and SF-12 interference with social activities (50.0 vs 11.5%, P = 0.0030) at six months. ABC participants were less likely to take muscle relaxants (16.7 vs 42.3%, P = 0.0481). Descriptively, UC participants were more likely to experience pain-related emergency room visits (45.8% vs 30.8%) and to be exposed to non-COX2 nonsteroidal anti-inflammatory drugs (73.1% vs 54.2%).

Conclusions
These preliminary data suggest that ABC care for older veterans with CLBP is feasible and may reduce pain and exposure to other potential morbidity.
Quantitative Immunology for Physicists
Authors: Altan-Bonnet Grégoire , Mora Thierry , Walczak Aleksandra M. 
Published: July 2019

AbstractThe adaptive immune system is a dynamical, self-organized multiscale system that protects vertebrates from both pathogens and internal irregularities, such as tumours. For these reason it fascinates physicists, yet the multitude of different cells, molecules and sub-systems is often also petrifying. Despite this complexity, as experiments on different scales of the adaptive immune system become more quantitative, many physicists have made both theoretical and experimental contributions that help predict the behaviour of ensembles of cells and molecules that participate in an immune response. Here we review some recent contributions with an emphasis on quantitative questions and methodologies. We also provide a more general methods section that presents some of the wide array of theoretical tools used in the field.
The histone chaperone FACT induces Cas9 multi-turnover behavior and modifies genome manipulation in human cells
Authors: Wang Alan S. , Chen Leo , Wu R. Alex , Richardson Christopher D. , Gowen Benjamin G. , Kazane Katelynn R. , Vu Jonathan T. , Wyman Stacia K. , Shin Jiyung , Walter Johannes C. , Corn Jacob E. 
Published: July 2019

SummaryCas9 is a prokaryotic RNA-guided DNA endonuclease that binds substrates tightly in vitro but turns over rapidly when used to manipulate genomes in eukaryotic cells. Little is known about the factors responsible for dislodging Cas9 or how they influence genome engineering. Using a proximity labeling system for unbiased detection of transient protein interactions in cell-free Xenopus laevis egg extract, we identified the dimeric histone chaperone FACT as an interactor of substrate-bound Cas9. Immunodepletion of FACT subunits from extract potently inhibits Cas9 unloading and converts Cas9’s activity from multi-turnover to single-turnover. In human cells, depletion of FACT delays genome editing and alters the balance between indel formation and homology directed repair. Depletion of FACT also increases epigenetic marking by dCas9-based transcriptional effectors with concomitant enhancement of transcriptional modulation. FACT thus shapes the intrinsic cellular response to Cas9-based genome manipulation most likely by determining Cas9 residence times.
MUC5AC drives COPD exacerbation severity through amplification of virus-induced airway inflammation
Authors: Singanayagam Aran , Footitt Joseph , Kasdorf Benjamin T , Marczynski Matthias , Cross Michael T , Finney Lydia J , Trujillo Torralbo Maria-Belen , Calderazzo Maria , Zhu Jie , Aniscenko Julia , Clarke Thomas B , Molyneaux Philip L , Bartlett Nathan W , Moffatt Miriam F , Cookson William O , Wedzicha Jadwiga , Evans Christopher M , Lieleg Oliver , Mallia Patrick , Johnston Sebastian L 
Published: July 2019

ABSTRACTThe respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus that is rich in mucin glycoproteins. Disrupted mucus production is a cardinal feature of chronic respiratory diseases but how this alteration affect interactions between mucins and pathogens is complex and poorly understood. Here, we identify a central and unexpected role for the major airway mucin MUC5AC in pathogenesis of virus-induced exacerbations of chronic obstructive pulmonary disease (COPD). Virus induction of MUC5AC is augmented in COPD compared to healthy subjects, is enhanced in frequent exacerbators and correlates with inflammation, symptom severity and secondary bacterial infection during exacerbation. MUC5AC is functionally related to inflammation as MUC5AC-deficient (Muc5ac-/-) mice had attenuated rhinovirus-induced airway inflammation whilst exogenous MUC5AC glycoprotein administration augmented virus-induced inflammatory responses and bacterial load. Mechanistically, MUC5AC-augmentation of rhinovirus-induced inflammation occurred through release of extracellular adenosine triphosphate (ATP). Therapeutic suppression of virus-induced MUC5AC release using an epidermal growth factor receptor (EGFR) inhibitor ameliorated exaggerated pro-inflammatory responses in a mouse COPD exacerbation model. Collectively, these studies demonstrate previously unrecognised pro-inflammatory effects of MUC5AC during infection and thus highlight a key unforeseen role in driving COPD exacerbation severity.
TWO-SIGMA: a novel TWO-component SInGle cell Model-based Association method for single-cell RNA-seq data
Authors: Van Buren Eric , Hu Ming , Weng Chen , Jin Fulai , Li Yan , Wu Di , Li Yun 
Published: July 2019

AbstractIn this paper, we develop TWO-SIGMA, a TWO-component SInGle cell Model-based Association method for differential expression (DE) analyses in single-cell RNA-seq (scRNA-seq) data. The first component models the probability of “drop-out” with a mixed-effects logistic regression model and the second component models the (conditional) mean expression with a mixed-effects negative binomial regression model. TWO-SIGMA is extremely flexible in that it: (i) does not require a log-transformation of the outcome, (ii) allows for overdispersed and zero-inflated counts, (iii) accommodates a correlation structure between cells from the same biological sample via random effect terms, (iv) can analyze unbalanced designs (in which the number of cells does not need to be identical for all samples), (v) can control for additional sample-level and cell-level covariates including batch effects, (vi) provides interpretable effect size estimates, and (vii) enables general tests of DE beyond two-group comparisons. To our knowledge, TWO-SIGMA is the only method for analyzing scRNA-seq data that can simultaneously accomplish each of these features. Simulations studies show that TWO-SIGMA outperforms alternative regression-based approaches in both type-I error control and power enhancement when the data contains even moderate within-sample correlation. A real data analysis using pancreas islet single-cells exhibits the flexibility of TWO-SIGMA and demonstrates that incorrectly failing to include random effect terms can have dramatic impacts on scientific conclusions. TWO-SIGMA is implemented in the R package twosigma available at https://github.com/edvanburen/twosigma.
Notes on the endemic cloud forest plants of the Cameroon Highlands and the new, Endangered,Tricalysia elmar(Coffeeae-Rubiaceae)
Authors: Cheek Martin , Causon Isla , Tchiengue Barthelemy , House Eden 
Published: July 2019

ABSTRACTBackground and aimsThis paper reports a further discovery in the context of a long-term botanical survey in the Cross River-Sanaga interval of west-central Africa, focussing on species discovery and conservation.MethodsNormal practices of herbarium taxonomy have been applied to study the material collected. The relevant collections are stored in the Herbarium of the Royal Botanic Gardens, Kew, London and at the Institute of Research in Agronomic Development – National Herbarium of Cameroon.Key resultsNew species to science continue to be discovered from the cloud (submontane) forests of the Cameroon Highlands in Cameroon. Most of these species are rare, highly localised, and threatened by habitat destruction. These discoveries increase the justification for improved conservation management of surviving habitat.Tricalysia elmarCheek (Coffeeae-Rubiaceae) is described as an additional species new to science and is compared with similar species of the genus. Restricted so far to four locations, Mt Kupe, Bali Ngemba, Lebialem and Nta Ali, its conservation status is assessed as Endangered (EN B1+2ab(iii)) according to the 2012 criteria of IUCN.
NASQAR: A web-based platform for high-throughput sequencing data analysis and visualization
Authors: Yousif Ayman , Drou Nizar , Rowe Jillian , Khalfan Mohammed , Gunsalus Kristin C 
Published: July 2019

AbstractBackgroundAs high-throughput sequencing applications continue to evolve, the rapid growth in quantity and variety of sequence-based data calls for the development of new software libraries and tools for data analysis and visualization. Often, effective use of these tools requires computational skills beyond those of many researchers. To ease this computational barrier, we have created a dynamic web-based platform, NASQAR (Nucleic Acid SeQuence Analysis Resource).ResultsNASQAR offers a collection of custom and publicly available open-source web applications that make extensive use of a variety of R packages to provide interactive data analysis and visualization. The platform is publicly accessible at http://nasqar.abudhabi.nyu.edu/. Open-source code is on GitHub at https://github.com/nasqar/NASQAR, and the system is also available as a Docker image at https://hub.docker.com/r/aymanm/nasqarall. NASQAR is a collaboration between the core bioinformatics teams of the NYU Abu Dhabi and NYU New York Centers for Genomics and Systems Biology.ConclusionsNASQAR empowers non-programming experts with a versatile and intuitive toolbox to easily and efficiently explore, analyze, and visualize their Transcriptomics data interactively. Popular tools for a variety of applications are currently available, including Transcriptome Data Preprocessing, RNA-seq Analysis (including Single-cell RNA-seq), Metagenomics, and Gene Enrichment.
PIN FORMED 2 facilitates the transport of Arsenite inArabidopsis thaliana
Authors: Ashraf Mohammad Arif , Umetsu Kana , Ponomarenko Olena , Saito Michiko , Aslam Mohammad , Antipova Olga , Dolgova Natalia , Kiani Cheyenne D. , Nezhati Susan , Tanoi Keitaro , Minegishi Katsuyuki , Nagatsu Kotaro , Kamiya Takehiro , Fujiwara Toru , Luschnig Christian , Tanino Karen , Pickering Ingrid , George Graham N. , Rahman Abidur 
Published: July 2019

AbstractArsenic contamination is a major environmental issue as it may lead to serious health hazard. Reduced trivalent form of inorganic arsenic, arsenite, is in general more toxic to plants compared with the fully oxidized pentavalent arsenate. The uptake of arsenite in plants has been shown to be mediated through a large subfamily of plant aquaglyceroporins, nodulin 26-like intrinsic proteins (NIPs). However, the efflux mechanisms, as well as the mechanism of arsenite-induced root growth inhibition, remain poorly understood. Using molecular physiology, synchrotron imaging, and root transport assay approaches, we show that the cellular transport of trivalent arsenicals inArabidopsis thalianais strongly modulated by PIN FORMED 2 (PIN2) auxin efflux transporter. Direct transport assay using radioactive arsenite, X-ray fluorescence imaging (XFI) coupled with X-ray absorption spectroscopy (XAS), and ICP-MS analysis revealed thatpin2plants accumulate higher concentrations of arsenite in root compared to wild-type. At the cellular level, arsenite specifically targets intracellular cycling of PIN2 and thereby alters the cellular auxin homeostasis. Consistently, loss of PIN2 results in aresenite hypersensitivity in root. XFI coupled with XAS further revealed that loss of PIN2 results in specific accumulation of arsenical species, but not the other metals like iron, zinc or calcium in the root tip. Collectively, these results demonstrate that PIN2 serves as a putative transporter of arsenical speciesin planta.
Systematic variation in marine dissolved organic matter stoichiometry and remineralization ratios as a function of lability
Authors: Zakem Emily J. , Levine Naomi M. 
Published: July 2019

AbstractRemineralization of organic matter by heterotrophic organisms regulates the biological sequestration of carbon, thereby mediating atmospheric CO2. While surface nutrient supply impacts the elemental ratios of primary production, stoichiometric control by remineralization remains unclear. Here we develop a mechanistic description of remineralization and its stoichiometry in a marine microbial ecosystem model. The model simulates the observed elemental plasticity of phytoplankton and the relatively constant, lower C:N of heterotrophic biomass. In addition, the model captures the observed decreases in DOC:DON and the C:N remineralization ratio with depth for more labile substrates, which are driven by a switch in the dominant source of labile DOM from phytoplankton to heterotrophic biomass. Only a model version with targeted remineralization of N-rich components is able to simulate the observed profiles of preferential remineralization of DON relative to DOC and the elevated C:N of bulk DOM. The model suggests that more labile substrates are associated with C-limited heterotrophic growth and not with preferential remineralization, while more recalcitrant substrates are associated with growth limited by processing rates and with preferential remineralization. The resulting patterns of variable remineralization stoichiometry mediate the extent to which a proportional increase in carbon production resulting from changes in phytoplankton stoichiometry can increase the efficiency of the biological pump. Results emphasize the importance of understanding the physiology of both phytoplankton and heterotrophs for anticipating changes in biologically driven ocean carbon storage.
A direct role for SNX9 in the biogenesis of filopodia
Authors: Jarsch IK , Gadsby JR , Nuccitelli A , Mason J , Shimo H , Pilloux L , Marzook B , Mulvey CM , Dobramysl U , Lilley KS , Hayward RD , Vaughan TJ , Dobson CL , Gallop JL 
Published: July 2019

SummaryFilopodia are finger-like actin-rich protrusions that extend from the cell surface and are important for cell-cell communication and pathogen internalization. The small size and transient nature of filopodia combined with shared usage of actin regulators within cells confounds attempts to identify filopodial proteins. Here, we used phage display phenotypic screening to isolate antibodies that alter the actin morphology of filopodia-like structuresin vitro. We found that all of the antibodies that cause shorter FLS interact with SNX9, an actin regulator that binds phosphoinositides during endocytosis and in invadopodia. In cells, we discover SNX9 at specialised filopodia inXenopusdevelopment and that SNX9 is an endogenous component of filopodia that are hijacked byChlamydiaentry. We show the use of antibody technology to identify proteins used in filopodia-like structures, and a role for SNX9 in filopodia.
Analysis of stochastic timing of intracellular events with gene switching
Authors: Ghusinga Khem Raj , Singh Abhyudai 
Published: July 2019

AbstractAn important step in execution of several cellular processes is accumulation of a regulatory protein up to a specific threshold level. Since production of a protein is inherently stochastic, the time at which its level crosses a threshold exhibits cell-to-cell variation. A problem of interest is to characterize how the statistics of event timing is affected by various steps of protein expression. Our previous work studied this problem by considering a gene expression model where gene was always active. Here we extend our analysis to a scenario where gene stochastically switches between active and inactive states. We formulate event timing as the first-passage time for a protein’s level to cross a threshold and investigate how the rates of gene activation/inactivation affect the distribution and moments of the first-passage time. Our results show that both the time-scale of gene switching with respect to the protein degradation rate as well as the ratio of the gene inactivation to gene activation rates are important parameters in shaping the event-timing distribution.
Quantification ofnosZgenes and transcripts in activated sludge microbiomes with novel group-specific qPCR methods validated with metagenomic analyses
Authors: Kim DaeHyun D. , Park Doyoung , Yoon Hyun , Yun Taeho , Song Min Joon , Yoon Sukhwan 
Published: July 2019

AbstractSubstantial N2O emission results from activated sludge nitrogen removal processes. The importance of N2O-reducers possessing NosZ-type N2O reductases have been recognized as the only N2O sinkin situkey to determination of the net N2O emissions; however, reliable quantification methods fornosZgenes and transcripts have yet to be developed. Here,nosZgenes and transcripts in activated sludge tank microbiomes were analyzed with the group-specific qPCR assays designedde novocombining culture-based and computational approach. A sewage sample was enriched in a batch reactor fed continuous stream of N2containing 20-10,000 ppmv N2O, where 14 genera of potential N2O-reducers were identified. All available amino acid sequences of NosZ affiliated to these taxa were grouped into five subgroups (two clade I and three clade II groups), and primer/probe sets exclusively and comprehensively targeting the subgroups were designed and validated within silicoPCR. Four distinct activated sludge samples from three different wastewater treatment plants in Korea were analyzed with the qPCR assays and the results were validated by comparison with the shotgun metagenome analysis results. With the validated qPCR assays, thenosZgenes and transcripts of six additional activated sludge samples were analyzed and the results of the analyses clearly indicated the dominance of two clade IInosZsubgroups (Flavobacterium-like andDechloromonas-like) among bothnosZgene and transcript pools.
Composition and Diversity of CRISPR-Cas13a systems in the genus Leptotrichia
Authors: Watanabe Shinya , Cui Bintao , Kiga Kotaro , Aiba Yoshifumi , Tan Xin-Ee , Sato’o Yusuke , Kawauchi Moriyuki , Boonsiri Tanit , Thitiananpakorn Kanate , Taki Yusuke , Li Fen-Yu , Azam Aa Haeruman , Nakada Yumi , Sasahara Teppei , Cui Longzhu 
Published: July 2019

AbstractClustered regularly interspaced short palindromic repeats (CRISPR)-Cas13a, previously known as CRISPR-C2c2, is the most recently identified RNA-guided RNA-targeting CRISPR-Cas system and has the unique characteristics of both targeted and collateral single-stranded RNA (ssRNA) cleavage activities, which was first identified in Leptotrichia shahii CRISPR-Cas13a. Here, the complete whole genome sequences of 11 Leptotrichia strains were determined and compared with 18 publicly available Leptotrichia genomes in regard to the composition, occurrence and diversity of the CRISPR-Cas13a and other CRISPR-Cas systems. Various types of CRISPR-Cas systems, I-B, II-C, III-A, III-D, III-like and VI-A, were unevenly distributed among the Leptotrichia genomes, accounting for 10 (34.4%), 1 (2.6%), 6 (15.4%), 6 (15.4%), 3 (7.7%) and 11 (37.9%) of the 29 strains, respectively, while 8 (20.5%) strains had no CRISPR-Cas system. The Cas13a effectors were highly divergent with amino acid sequence similarities ranging from 61% to 90% to that of L. shahii and their collateral ssRNA cleavage activities, resulting in cytotoxicity to host cell, were found to be maintained. CRISPR-Cas spacers represent a sequential achievement of former intruder encounters, and the retained spacers reflect the evolutionary phylogeny or relatedness of strains. Analysis of spacer contents and numbers among Leptotrichia species showed considerable diversity with only 2 (0.5%) of 400 spacers through CRIPSR-Cas I-VI were shared by two strains. The organisation and distribution of CRISPR-Cas systems (type I-VI) encoded by all registered Leptotrichia species revealed that effector or spacer sequences of the CRISPR-Cas systems were very divergent, and the prevalence of types I, III and VI was almost equal. There was only one strain carrying type II, while none carried type IV or V. These results provide new insights into the characteristics and divergences of CRISPR-Cas systems among Leptotrichia species.
MGSE regulates crosstalk from the mucin pathway to the TFE3 pathway of the Golgi stress response
Authors: Jamaludin Mohamad Ikhwan , Wakabayashi Sadao , Sasaki Kanae , Komori Ryota , Kawamura Hirotada , Takase Hayataka , Sakamoto Miyu , Yoshida Hiderou 
Published: July 2019

AbstractThe Golgi apparatus is an organelle where membrane or secretory proteins receive post-translational modifications such as glycosylation and sulfation, after which the proteins are selectively transported to their final destinations through vesicular transport. When the synthesis of secretory or membrane proteins is increased and overwhelms the capacity of the Golgi (Golgi stress), eukaryotic cells activate a homeostatic mechanism called the Golgi stress response to augment the capacity of the Golgi. Four response pathways of the Golgi stress response have been identified, namely the TFE3, CREB3, HSP47, and proteoglycan pathways, which regulate the general function of the Golgi, apoptosis, cell survival, and proteoglycan glycosylation, respectively. Here, we identified a novel response pathway that augments the expression of glycosylation enzymes for mucins in response to insufficiency in mucin-type glycosylation in the Golgi (mucin-type Golgi stress), and we found that expression of glycosylation enzymes for mucins such as GALNT5, GALNT8, and GALNT18 was increased upon mucin-type-Golgi stress. We named this pathway the mucin pathway. Unexpectedly, mucin-type Golgi stress induced the expression and activation of TFE3, a key transcription factor regulating the TFE3 pathway, suggesting that the activated mucin pathway sends a crosstalk signal to the TFE3 pathway. We identified an enhancer element regulating transcriptional induction of TFE3 upon mucin-type Golgi stress, and named it the mucin-type Golgi stress response element, of which consensus was ACTTCC(N9)TCCCCA. These results suggested that crosstalk from the mucin pathway to the TFE3 pathway has an important role in the regulation of the mammalian Golgi stress response.