bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Fecal Lactobacillus Is Associated With a Positive Glucose Hydrogen Breath Test in Bangladeshi Children
Authors: Donowitz Jeffrey R , Parikh Hardik I , Taniuchi Mami , Gilchrist Carol A , Haque Rashidul , Kirkpatrick Beth D , Alam Masud , Kakon Shahria Hafiz , Islam Bushra Zarin , Afreen Sajia , Kabir Mamun , Nayak Uma , Colgate E Ross , Carmolli Marya P , Petri William A 
Published: June 2019

Abstract

Background
Glucose hydrogen breath testing is a noninvasive test for small intestine bacterial overgrowth (SIBO). A positive glucose hydrogen breath test is common in children from low-income countries and has been found to be associated with malnutrition as measured by stunted growth. The microbiome associated with positive breath testing is relatively unstudied.

Methods
We performed 16 S V4 rDNA microbiome analysis on the stool of 90 Bangladeshi children aged 2 years from an impoverished neighborhood who were tested at the same time for SIBO by glucose hydrogen breath testing. Data were analyzed by linear discriminant analysis effect size with SIBO as the outcome. Any selected genera were tested individually by Wilcoxon’s rank-sum test to ensure that linear discriminant analysis effect size results were not outlier-skewed.

Results
Linear discriminant analysis effect size analysis identified Lactobacillus (linear discriminate analysis score, 4.59; P = .03) as over-represented in 15 out of the 90 children who were SIBO positive.

Conclusions
These results suggest that glucose hydrogen breath test positivity in children from low-income settings may be due to an upper intestinal Lactobacillus bloom, potentially explaining the association of SIBO with the gut damage and inflammation that leads to malnutrition.
Transcutaneous Electrical Nerve Stimulation Reduces Knee Osteoarthritic Pain by Inhibiting Spinal Glial Cells in Rats
Authors: Hahm Suk-Chan , Song Eseul , Jeon Hochung , Yoon Young Wook , Kim Junesun 
Published: June 2019

AbstractBackgroundTranscutaneous electrical nerve stimulation (TENS) is commonly used for pain control. However, the effects of TENS on osteoarthritis (OA) pain and potential underlying mechanisms remain unclear.ObjectiveThe objective of this study was to investigate the effect of TENS on OA pain treatment and underlying mechanisms related to glial cell inhibition.DesignThis was an experimental study.MethodsOA was induced by injection of monosodium iodoacetate into the synovial space of the right knee joint of rats. High-frequency (HF) TENS (100 Hz), low-frequency (LF) TENS (4 Hz), or sham TENS was applied to the ipsilateral knee joint for 20 minutes. Paw withdrawal threshold (PWT), weight bearing, and knee bend score (KBS) were measured. Immunohistochemistry for microglia and astrocytes was performed with L3 to L5 spinal segment samples. To investigate the effects of glial inhibition on OA pain, minocycline, l-α-aminoadipate, or artificial cerebrospinal fluid was injected intrathecally, and PWT and KBS were measured.ResultsCompared with sham TENS, both HF TENS and LF TENS significantly increased PWT, decreased KBS, and inhibited activated microglia in the L3 to L5 segments but did not decrease the total number of microglia, except in the L4 segment (HF TENS). Astrocyte expression was significantly decreased in the L3 to L5 segments following LF TENS and in the L3 segment following HF TENS. Compared with artificial cerebrospinal fluid, both minocycline and l-α-aminoadipate increased PWT and decreased KBS.LimitationsThese results cannot be generalized to humans.ConclusionsTENS alleviates OA pain in rats by inhibiting activated microglia and reducing astrocyte expression in the spinal cord. Although these results may not be generalizable to chronic pain in patients with OA, within the limitation of the experimental animal model used in the present study, they suggest a possible mechanism and preclinical evidence supporting further experimentation or clinical use of TENS in humans.
Evolution of Plasmodium falciparum drug resistance genes following artemisinin combination therapy in Sudan
Authors: Bakhiet Amani M A , Abdelraheem Mohamed H , Kheir Amani , Omer Samia , Gismelseed Linda , Abdel-Muhsin Abdel-Muhsin A , Naiem Ahmed , Al Hosni Ahmed , Al Dhuhli Amani , Al Rubkhi Maymona , Al-Hamidhi Salama , Gadalla Amal , Mukhtar Moawia , Sultan Ali A , Babiker Hamza A 
Published: June 2019

Abstract

Background
Malaria control efforts in Sudan rely heavily on case management. In 2004, health authorities adopted artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. However, some recent surveys have reported ACT failure and a prevalent irrational malaria treatment practice. Here we examine whether the widespread use of ACT and failure to adhere to national guidelines have led to the evolution of drug resistance genes.

Methods
We genotyped known drug resistance markers (Pfcrt, Pfmdr-1, Pfdhfr, Pfdhps, Pfk13 propeller) and their flanking microsatellites among Plasmodium falciparum isolates obtained between 2009 and 2016 in different geographical regions in Sudan. Data were then compared with published findings pre-ACT (1992–2003).

Results
A high prevalence of Pfcrt76T, Pfmdr-1-86Y, Pfdhfr51I, Pfdhfr108N, Pfdhps37G was observed in all regions, while no Pfk13 mutations were detected. Compared with pre-ACT data, Pfcrt-76T and Pfmdr-1-86Y have decayed, while Pfdhfr-51I, Pfdhfr-108N and Pfdhps-437G strengthened. Haplotypes Pfcrt-CVIET, Pfmdr-1-NFSND/YFSND, Pfdhfr-ICNI and Pfdhps-SGKAA predominated in all sites. Microsatellites flanking drug resistance genes showed lower diversity than neutral ones, signifying high ACT pressure/selection.

Conclusions
Evaluation of P. falciparum drug resistance genes in Sudan matches the drug deployment pattern. Regular monitoring of these genes, coupled with clinical response, should be considered to combat the spread of ACT resistance.
Phanerozoic Radiation of Ammonia Oxidizing Bacteria
Authors: Ward LM , Johnston DT , Shih PM 
Published: June 2019

AbstractThe modern nitrogen cycle consists of a web of microbially mediated redox transformations. Among the most crucial reactions in this cycle is the oxidation of ammonia to nitrite, an obligately aerobic process performed by a limited number of lineages of bacteria (AOB) and archaea (AOA). As this process has an absolute requirement for O2, the timing of its evolution – especially as it relates to the Great Oxygenation Event ~2.3 billion years ago – remains contested and is pivotal to our understanding of nutrient cycles. To estimate the antiquity of bacterial ammonia oxidation, we performed phylogenetic and molecular clock analyses of AOB. Surprisingly, bacterial ammonia oxidation appears quite young, with crown group clades having originated during Neoproterozoic time (or later) with major radiations occurring during Paleozoic time. These results place the evolution of AOB broadly coincident with the pervasive oxygenation of the deep ocean. The late evolution AOB challenges earlier interpretations of the ancient nitrogen isotope record, predicts a more substantial role for AOA during Precambrian time, and may have implications for understanding of the size and structure of the biogeochemical nitrogen cycle through geologic time.
A novel role for Myosin-Va in mitochondrial fission
Authors: Araujo Jackeline S , Silva-Junior Rui M P , Zhang Tong , Schiavon Cara R , Chu Qian , Wu Melissa , Pontes Carmen L S , Souza Anderson O , Alberici Luciane C , Santos Aline M , Ingle Sadie Bartholomew , Saghatelian Alan , Spudich James , Manor Uri , Espreafico Enilza M 
Published: June 2019

ABSTRACTIn cancer cells metabolic changes and mitochondrial morphology are coupled. It is known that the cytoskeleton and molecular motors are directly involved in regulating mitochondrial morphology. Here we show that myosin-Va, an actin-based molecular motor, is required for the malignant properties of melanoma cells and localizes to mitochondria in these cells. Knockdown of myosin-Va increases cellular respiration rates and ROS production and decreases glucose uptake and lactate secretion. In addition, knockdown of myosin-Va results in reduced mitochondrial fission and correspondingly elongated mitochondria. We show that myosin-Va interacts with the mitochondrial outer membrane protein Spire1C, an actin-regulatory protein implicated in mitochondrial fission, and that Spire1C recruits myosin-Va to mitochondria. Finally, we show that during mitochondrial fission myosin-Va localization to mitochondria increases, and that myosin-Va localizes to mitochondrial fission sites immediately adjacent to Drp1 punctae. We conclude that myosin-Va facilitates mitochondrial fission. These data implicate myosin-Va as a target for the Warburg effect in melanoma cells.
An immunome perturbation is present in juvenile idiopathic arthritis patients who are in remission and will relapse upon anti-TNFα withdrawal
Authors: Leong Jing Yao , Chen Phyllis , Yeo Joo Guan , Ally Fauziah , Chua Camillus , Hazirah Sharifah Nur , Poh Su Li , Pan Lu , Lai Liyun , Lee Elene Seck Choon , Bathi Loshinidevi D/O Thana ,   PRCSG, Arkachaisri Thaschawee , Lovell Daniel J. , Albani Salvatore 
Published: June 2019

ABSTRACTObjectivesBiologics treatment with anti-TNFα is efficacious in juvenile idiopathic arthritic (JIA) patients. Despite displaying clinical inactivity during treatment, many patients will flare upon cessation of therapy. The inability to definitively discriminate patients who will relapse or continue to remain in remission after therapy withdrawal is currently a major unmet medical need. CD4 T cells have been implicated in active disease, yet how they contribute to disease persistence despite treatment is unknown.MethodsWe interrogated the circulatory reservoir of CD4+ immune subsets at the single cell resolution with mass cytometry (CyToF) of JIA patients (n=20) who displayed continuous clinical inactivity for at least 6 months with anti-TNFα, and were subsequently withdrawn from therapy for 8 months, and scored as relapse or remission. These patients were examined prior to therapy withdrawal for putative subsets that could discriminate relapse from remission. We verified on a separate JIA cohort (n=16), the continued dysregulation of these circulatory subsets 8 months into therapy withdrawal. The immunological transcriptomic signature of CD4 memory in relapse/remission patients was examined with Nanostring.ResultsAn inflammatory memory subset of CD3+CD4+CD45RA−TNFα+ T cells deficient in immune checkpoints (PD1−CD152−) was present in relapse patients prior to therapy withdrawal. Transcriptomic profiling reveals divergence between relapse and remission patients in disease centric pathways involving (a) TCR activation, (b) apoptosis, (c) TNFα, (d) NF-kB and (e) MAPK signalling.ConclusionsA unique discriminatory immunomic and transcriptomic signature is associated with relapse patients and may explain how relapse occurs.
The absence of F-box motif Encoding Gene SAF1 and Chromatin Associated factor CTF8 together contributes to MMS Resistant and HU Sensitive phenotype in S.cerevisiae
Authors: Sharma Meenu , Verma V. , Bairwa Narendra K 
Published: June 2019

AbstractThe Replication factor-C compex which related to cohesion, constitutes, three subunits called Ctf18, Ctf8 and Dcc1. These three subunit complex assist the loading of PCNA onto the chromosome. None of the replication factor C components are essential for cell viability. The null mutant of the CTF8 inS.cerevisiaeshows the chromosome instability and high frequency of chromosome loss. The SAF1 gene product of S.cerevisiaeinvolved in the degradation of adenine deaminase factor Aah1p by SCF-E3 ligase, which itself is the part of E3 ligase. The ubiquitin marked degradation of Aah1p occurs during nutrient stress which lead to cell enter into the quiescent state. The N-terminus of Saf1p interacts with the Skp1 of SCF-E3 ligase and at C-terminus recruits with Aah1p. Here we have investigated about the binary genetic interaction between the SAF1 and CTF8 genes. The strains containing single and double gene deletions of SAF1 and CTF8 were constructed in the BY4741 genetic background. Further the mutant strains were evaluated for growth fitness, genome stability and response to genotoxic stress caused by hydroxyurea (HU) and methyl methane sulfonate (MMS). Thesaf1Δctf8Δstrain showed the increased growth phenotype in comparison tosaf1Δ, ctf8Δ, andWT strain on YPD medium. Howeversaf1Δctf8Δstrain when grown in the presence MMS showed resistance and HU sensitive phenotype when compared withsaf1Δ, ctf8Δ.The frequency of Ty1 retro-transposition was also elevated insaf1Δctf8Δin comparison to eithersaf1Δorctf8Δ.The number of cells showing the two or multi-nuclei phenotype was also increased insaf1Δctf8Δcells when compared with the eithersaf1Δorctf8Δ.Based on these observations, we report that the absence of both the gene SAF1 and CTF8 together leads to MMS resistance, HU sensitivity, and genome instability. This report warrants the investigation of mechanisms of differential growth phenotype due to loss of SAF1 and CTF8 together in presence of genotoxic stress in future.
Scalable Spike Source Localization in Extracellular Recordings using Amortized Variational Inference
Authors: Hurwitz Cole L. , Xu Kai , Srivastava Akash , Buccino Alessio P. , Hennig Matthias H. 
Published: June 2019

AbstractDetermining the positions of neurons in an extracellular recording is useful for investigating functional properties of the underlying neural circuitry. In this work, we present a Bayesian modelling approach for localizing the source of individual spikes on high-density, microelectrode arrays. To allow for scalable inference, we implement our model as a variational autoencoder and perform amortized variational inference. We evaluate our method on both biophysically realistic simulated and real extracellular datasets, demonstrating that it is more accurate than and can improve spike sorting performance over heuristic localization methods such as center of mass.
SPECS: A non-parameteric method to identify tissue-specific molecular features for unbalanced sample groups
Authors: Everaert Celine , Volders Pieter-Jan , Morlion Annelien , Thas Olivier , Mestdagh Pieter 
Published: June 2019

AbstractTo understand biology and differences among various tissues or cell types, one typically searches for molecular features that display characteristic abundance patterns. Several specificity metrics have been introduced to identify tissue-specific molecular features, but these either require an equal number of replicates per tissue or they can’t handle replicates at all. We describe a non-parametric specificity score that is compatible with unequal sample group sizes. To demonstrate its usefulness, the specificity score was calculated on all GTEx samples, detecting known and novel tissue-specific genes. A webtool was developed to browse these results for genes or tissues of interest. An example python implementation of SPECS is available at https://github.ugent.be/ceeverae/SPECs. The precalculated SPECS results on the GTEx data are available through a user-friendly browser at specs.cmgg.be.
Mind the gap: micro-expansion joints drastically decrease the bending of FIB-milled cryo-lamellae
Authors: Wolff Georg , Limpens Ronald W. A. L. , Zheng Shawn , Snijder Eric J. , Agard David A. , Koster Abraham J. , Bárcena Montserrat 
Published: June 2019

AbstractCryo-focussed ion beam (FIB)-milling of biological samples can be used to generate thin electron-transparent slices from cells grown or deposited on EM grids. These so called cryo-lamellae allow high-resolution structural studies of the natural cellular environment by in situ cryo-electron tomography. However, the cryo-lamella workflow is a low-throughput technique and can easily be obstructed by technical issues like the bending of the lamellae during the final cryo-FIB-milling steps. The severity of lamella bending seems to correlate with shrinkage of the EM grid support film at cryogenic temperatures, which could generate tensions that may be transferred onto the thin lamella, leading to its bending and breakage. To protect the lamellae from these forces, we milled “micro-expansion joints” alongside the lamellae, creating gaps in the support that can act as physical buffers to safely absorb material motion. We demonstrate that the presence of such micro-expansion joints drastically decreases lamella bending. Furthermore, we show that this adaptation does not create instabilities that could constrain subsequent parts of the cryo-lamella workflow, as we obtained high-quality Volta phase plate tomograms revealing macromolecules in their natural structural context. The minimal additional effort required to implement micro-expansion joints in the cryo-FIB-milling workflow makes them an easy solution against cryo-lamella bending in any biological sample milled on EM grids.
functionInk: An efficient method to detect functional groups in multidimensional networks reveals the hidden structure of ecological communities
Authors: Pascual-García Alberto , Bell Thomas 
Published: June 2019

AbstractComplex networks have been useful to link experimental data with mechanistic models, and have become widely used across many scientific disciplines. Recently, the increasing amount and complexity of data, particularly in biology, has prompted the development of multidimensional networks, where dimensions reflect the multiple qualitative properties of nodes, links, or both. As a consequence, traditional quantities computed in single dimensional networks should be adapted to incorporate this new information. A particularly important problem is the detection of communities, namely sets of nodes sharing certain properties, which reduces the complexity of the networks, hence facilitating its interpretation.In this work, we propose an operative definition of “function” for the nodes in multidimensional networks, and we exploit this definition to show that it is possible to detect two types of communities: i) modules, which are communities more densely connected within their members than with nodes belonging to other communities, and ii) guilds, which are sets of nodes connected with the same neighbours, even if they are not connected themselves. We provide two quantities to optimally detect both types of communities, whose relative values reflect their importance in the network.The flexibility of the method allowed us to analyze different ecological examples encompassing mutualistic, trophic and microbial networks. We showed that by considering both metrics we were able to obtain deeper ecological insights about how these different ecological communities were structured. The method mapped pools of species with properties that were known in advance, such as plants and pollinators. Other types of communities found, when contrasted with external data, turned out to be ecologically meaningful, allowing us to identify species with important functional roles or the influence of environmental variables. Furthermore, we found the method was sensitive to community-level topological properties like the nestedness.In ecology there is often a need to identify groupings including trophic levels, guilds, functional groups, or ecotypes.The method is therefore important in providing an objective means of distinguishing modules and guilds. The method we developed, functionInk (functional linkage), is computationally efficient at handling large multidimensional networks since it does not require optimization procedures or tests of robustness. The method is available at: HTTPS://GITHUB.COM/APASCUALGARCIA/FUNCTIONINK.
The Impact of Antimalarial Resistance on the Genetic Structure ofPlasmodium falciparumin the DRC
Authors: Verity Robert , Aydemir Ozkan , Brazeau Nicholas F. , Watson Oliver J. , Hathaway Nicholas J. , Kashamuka Mwandagalirwa Melchior , Marsh Patrick W. , Thwai Kyaw , Fulton Travis , Denton Madeline , Morgan Andrew P. , Parr Jonathan B. , Tumwebaze Patrick K. , Conrad Melissa , Rosenthal Philip J. , Ishengoma Deus S. , Ngondi Jeremiah , Gutman Julie , Mulenga Modest , Norris Douglas E. , Moss William J. , Mensah Benedicta A , Myers-Hansen James L , Ghansah Anita , Tshefu Antoinette K , Ghani Azra C. , Meshnick Steven R. , Bailey Jeffrey A. , Juliano Jonathan J. 
Published: June 2019

ABSTRACTThe Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequenced 2537Plasmodium falciparuminfections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a novel high-throughput genotyping tool. We identified an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identified highly related parasites over large geographic distances, indicative of gene flow and migration. Our results were consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.
Nubp2is required for cranial neural crest survival in the mouse
Authors: DiStasio Andrew , Paulding David , Chatuverdi Praneet , Stottmann Rolf W. 
Published: June 2019

AbstractThe N-ethyl-N-nitrosourea (ENU) forward genetic screen is a useful tool for the unbiased discovery of novel mechanisms regulating developmental processes. We recovered thedorothymutation in such a screen designed to recover recessive mutations affecting craniofacial development in the mouse.Dorothyembryos die prenatally and exhibit many striking phenotypes commonly associated with ciliopathies, including a severe midfacial clefting phenotype. We used exome sequencing to discover a missense mutation in Nucleotide Binding Protein 2 (Nubp2) to be causative. This finding was confirmed with a complementation analysis between thedorothyallele and aNubp2null allele (Nubp2Null). We demonstrate thatNubp2is indispensable for embryogenesis. NUBP2 is implicated in both the Cytosolic Iron/Sulfur cluster Assembly (CIA) pathway and in the negative regulation of ciliogenesis. Conditional ablation ofNubp2in the neural crest lineage withWnt1-crerecapitulates thedorothycraniofacial phenotype. Using this model, we found that the proportion of ciliated cells in the craniofacial mesenchyme was unchanged, and that markers of the Shh, Fgf, and Bmp signaling pathways are unaltered. Finally, we show that the phenotype results from a marked increase in apoptosis within the craniofacial mesenchyme.Summary StatementAn ENU screen identifies a novel allele ofNubp2which is then demonstrated to be required for cranial neural crest survival and proper midfacial development.