bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disinfectant residuals in drinking water systems select for mycobacterial populations with intrinsic antimicrobial resistance
Authors: Sevillano Maria , Dai Zihan , Calus Szymon , Bautista-de los Santos Quyen M , Eren A. Murat , van der Wielen Paul W.J.J. , Ijaz Umer Z. , Pinto Ameet J. 
Published: June 2019

AbstractAntimicrobial resistance (AMR) in drinking water has received less attention than counterparts in the urban water cycle. While culture-based techniques or gene-centric PCR have been used to probe the impact of treatment approaches (e.g., disinfection) on AMR in drinking water, to our knowledge there is no systematic comparison of AMR traits between disinfected and disinfectant residual-free drinking water systems. We use metagenomics to assess the associations between disinfectant residuals and AMR prevalence and its host association in full-scale drinking water distribution systems (DWDSs). The differences in AMR profiles between DWDSs are associated with the presence or absence of disinfectant. Further, AMR genes and mechanisms enriched in disinfected systems are associated with drug classes primarily linked to nontuberculous mycobacteria (NTM). Finally, evaluation of metagenome assembled genomes (MAGs) of NTM indicates that they possess AMR genes conferring intrinsic resistance to key antibiotics, whereas such NTM genomes were not detected in disinfectant residual free DWDSs. Thus, disinfection may not only influence the AMR profiles of the drinking water microbiome but also select for NTM with intrinsic AMR.
Genome assembly and characterization of a complex zfBED-NLR gene-containing disease resistance locus in Carolina Gold Select rice with Nanopore sequencing
Authors: Read Andrew C. , Moscou Matthew J. , Zimin Aleksey V. , Pertea Geo , Meyer Rachel S. , Purugganan Michael D. , Leach Jan E. , Triplett Lindsay R. , Salzberg Steven L. , Bogdanove Adam J. 
Published: June 2019

AbstractBackgroundLong-read sequencing facilitates assembly of complex genomic regions. In plants, loci containing nucleotide-binding, leucine-rich repeat (NLR) disease resistance genes are an important example of such regions. NLR genes make up one of the largest gene families in plants and are often clustered, evolving via duplication, contraction, and transposition. We recently mapped the Xo1 locus for resistance to bacterial blight and bacterial leaf streak, found in the American heirloom rice variety Carolina Gold Select, to a region that in the Nipponbare reference genome is rich in NLR genes.ResultsToward identification of the Xo1 gene, we combined Nanopore and Illumina reads to generate a high-quality genome assembly for Carolina Gold Select. We identified 529 full or partial NLR genes and discovered, relative to the reference, an expansion of NLR genes at the Xo1 locus. One NLR gene at Xo1 has high sequence similarity to the cloned, functionally similar Xa1 gene. Both harbor an integrated zfBED domain and near-identical, tandem, C-terminal repeats. Across diverse Oryzeae, we identified two sub-clades of such NLR genes, varying in the presence of the zfBED domain and the number of repeats.ConclusionsWhole genome sequencing combining Nanopore and Illumina reads effectively resolves NLR gene loci, providing context as well as content. Our identification of an Xo1 candidate is an important step toward mechanistic characterization, including the role(s) of the zfBED domain. Further, the Carolina Gold Select genome assembly will facilitate identification and exploitation of other useful traits in this historically important rice variety.
Redox-mediated Kick-Start of Mitochondrial Energy Metabolism drives Resource-efficient Seed Germination
Authors: Nietzel Thomas , Mostertz Jörg , Ruberti Cristina , Wagner Stephan , Moseler Anna , Fuchs Philippe , Müller-Schüssele Stefanie J. , Benamar Abdelilah , Poschet Gernot , Büttner Michael , Née Guillaume , Møller Ian Max , Lillig Christopher H. , Macherel David , Finkemeier Iris , Wirtz Markus , Hell Rüdiger , Meyer Andreas J. , Hochgräfe Falko , Schwarzländer Markus 
Published: June 2019

ABSTRACTSeeds preserve a far developed plant embryo in a quiescent state. Seed metabolism relies on stored resources and is re-activated to drive germination when the external conditions are favorable. Since the switchover from quiescence to re-activation provides a remarkable case of a cell physiological transition we investigated the earliest events in energy and redox metabolism ofArabidopsisseeds at imbibition. By developing fluorescent protein biosensing in intact seeds, we observed ATP accumulation and oxygen uptake within minutes, indicating rapid activation of mitochondrial respiration, which coincided with a sharp transition from an oxidizing to a more reducing thiol redox environment in the mitochondrial matrix. To identify individual operational protein thiol switches, we captured the fast release of metabolic quiescencein organelloand devised quantitative iodoacetyl tandem mass tag-based (iodoTMT) thiol redox proteomics. The redox state across all Cys-peptides was shifted towards reduction from 27.1 % to 13.0 %. A large number of Cys-peptides (412) were redox-switched, representing central pathways of mitochondrial energy metabolism, including the respiratory chain and each enzymatic step of the tricarboxylic acid cycle (TCA). Active site Cys-peptides of glutathione reductase 2, NADPH-thioredoxin reductase a/b and thioredoxin-o1 showed the strongest responses. Germination of seeds lacking those redox proteins was associated with markedly enhanced respiration and deregulated TCA cycle dynamics suggesting decreased resource efficiency of energy metabolism. Germination in aged seeds was strongly impaired. We identify a global operation of thiol redox switches that is required for optimal usage of energy stores by the mitochondria to drive efficient germination.
Gene Loss and Evolution of the Plastome
Authors: Mohanta Tapan Kumar , Mishra Awdhesh Kumar , Khan Adil , Hashem Abeer , Abd_Allah Elsayed Fathi , Al-Harrasi Ahmed 
Published: June 2019

AbstractChloroplasts are unique organelles within the plant cells and are responsible for sustaining life forms on the earth due to their ability to conduct photosynthesis. Multiple functional genes within the chloroplast are responsible for a variety of metabolic processes that occur in the chloroplast. Considering its fundamental role in sustaining life on the earth, it is important to identify the level of diversity present in the chloroplast genome, what genes and genomic content have been lost, what genes have been transferred to the nuclear genome, duplication events, and the overall origin and evolution of the chloroplast genome. Our analysis of 2511 chloroplast genomes indicated that the genome size and number of coding DNA sequences (CDS) in the chloroplasts genome of algae are higher relative to other lineages. Approximately 10.31% of the examined species have lost the inverted repeats (IR) in the chloroplast genome that span across all the lineages. Genome-wide analyses revealed the loss of the Rbcl gene in parasitic and heterotrophic plants occurred approximately 56 Ma ago. PsaM, Psb30, ChlB, ChlL, ChlN, and Rpl21 were found to be characteristic signature genes of the chloroplast genome of algae, bryophytes, pteridophytes, and gymnosperms; however, none of these genes were found in the angiosperm or magnoliid lineage which appeared to have lost them approximately 203–156 Ma ago. A variety of chloroplast-encoded genes were lost across different species lineages throughout the evolutionary process. The Rpl20 gene, however, was found to be the most stable and intact gene in the chloroplast genome and was not lost in any of the analyzed species, suggesting that it is a signature gene of the plastome. Our evolutionary analysis indicated that chloroplast genomes evolved from multiple common ancestors ~1293 Ma ago and have undergone vivid recombination events across different taxonomic lineages.
How does individual variation in sociality influence fitness in prairie voles?
Authors: Sabol Anne C. , Lambert Connor T. , Keane Brian , Solomon Nancy G. , Dantzer Ben 
Published: June 2019

AbstractComparative studies aid in our understanding of specific conditions favoring the initial evolution of different types of social behaviors, yet there is much unexplained intraspecific variation in the expression of social behavior that comparative studies have not yet addressed. The proximate causes of this individual variation in social behavior within a species have been examined in some species but its fitness consequences have been less frequently investigated. In this study, we quantified the fitness consequences of variation in the sociality of prairie voles (Microtus ochrogaster). We characterized sociality of voles in semi-natural enclosures using an automated behavioral tracking system paired with social network analyses to quantify the degree of spatial and temporal co-occurrence of different voles. We then assessed the relationship between sociality with mating success (number of different conspecifics with which an individual produced offspring) and reproductive success (total number of offspring surviving to first capture). We measured the number of social connections each individual had with all voles and only with opposite-sex voles by calculating unweighted degree through social network analyses. Both female and male voles varied in the number of social connections they had with all conspecifics and with opposite-sex conspecifics. Voles with an intermediate number of social connections with voles of both sexes had higher mating success overall. In our analyses that considered all social connections with voles of both sexes, voles with an intermediate number of social connections produced more offspring. Males with a very high or low number of social connections also had the lowest average body mass. Overall, our results suggest some limit on the fitness benefits of sociality. Although there was substantial individual-variation in our measure of vole social behavior, intermediate levels of social connections may be most favorable.
Scale-dependent effects of geography, host ecology, and host genetics on diversity of a stickleback parasite metacommunity
Authors: Bolnick Daniel I. , Resetarits Emlyn J. , Ballare Kimberly , Stuart Yoel E. , Stutz William E. 
Published: June 2019

AbstractMany metacommunities are distributed across habitat patches that are themselves aggregated into groups. Perhaps the clearest example of this nested metacommunity structure comes from multi-species parasite assemblages, which occupy individual hosts that are aggregated into host populations. At both spatial scales, we expect parasite community diversity in a given patch (either individual host or population) to depend on patch characteristics that affect colonization rates and species sorting. But, are these patch effects consistent across spatial scales? Or, do different processes govern the distribution of parasite community diversity among individual hosts, versus among host patches? To answer these questions, we document the distribution of parasite richness among host individuals and among populations in a metapopulation of threespine stickleback (Gasterosteus aculeatus). We find some host traits (host size, gape width) are associated with increased parasite richness at both spatial scales. Other patch characteristics affect parasite richness only among individuals (sex), or among populations (lake size, lake area, elevation, and population mean heterozygosity). These results demonstrate that some rules governing parasite richness in this metacommunity are shared across scales, while others are scale-specific.
EpiSort: Enumeration of cell types using targeted bisulfite sequencing
Authors: Aran Dvir , Dover Ron S. , Lundy Karen E. , Leipold Michael D. , Xuhuai Ji , McDevitt Shana L. , Davis Mark M. , Butte Atul J. 
Published: June 2019

AbstractThe cellular composition of tumors is now recognized as an essential phenotype, with implications to diagnostic, progression and therapy efficacy. A tool for accurate profiling of the tumor microenvironment is lacking, as single-cell methods and computational approaches are not applicable or suffer from low accuracy. Here we present EpiSort, a novel strategy based on targeted bisulfite sequencing, which allows the accurate enumeration of 23 cell types and may be applicable to cancer studies.
The C-terminal non-catalytic domain of Mkp-1 phosphatase harbors a complex signal for rapid proteasome degradation in enterocytes
Authors: Wang Jin , Grishin Anatoly , Delaplain Patrick T. , Gayer Christopher P. , Ford Henri R. 
Published: June 2019

AbstractMitogen-activated kinase phosphatase Mkp-1 is an essential negative regulator of innate immune responses. In enterocytes, Mkp-1, which is transiently expressed in response to Toll-like receptor (TLR) ligands, plays a role as an initial step in establishing tolerance to bacteria and their pro-inflammatory molecules. Mkp-1 has a very short half-life (about 30 min) in IEC-6 enterocytes. Here we examined the mechanism of Mkp-1 rapid degradation in IEC-6 cells. Immunoprecipitation and proteolysis inhibitor analysis indicated that Mkp-1 is monoubiquitinated and degraded by proteasome. Dominant negative ubiquitin increased Mkp-1 half-life, indicating involvement of ubiquitination in Mkp-1 degradation. Stability of Mkp-1 is not affected by LPS treatment, consistent with constitutive degradation. U0126, a potent and selective inhibitor of extracellular response kinase (ERK) had negligible effect on the stability of both intrinsic and ectopically expressed Mkp-1, therefore enterocytes, unlike other cell types, do not regulate Mkp-1 degradation via ERK-dependent phosphorylation. C-Truncations of the C-terminal non-catalytic domain (at amino acids 306, 331, and 357), the 306-330 deletion obliterating the potential PEST domains, as well as S296A mutation, but not S323A, S358A, or S363A mutations in potential ERK phosphorylation sites dramatically stabilized Mkp-1. C-terminal fusion of the non-catalytic C-terminal domain of Mkp-1 conferred accelerated degradation on the intrinsically stable green fluorescent protein. According to these results, rapid degradation of Mkp-1 in IEC-6 enterocytes is ubiquitin-proteasome-dependent and ERK-independent. Multiple elements of the C-terminal non-catalytic domain play essential roles in the formation of the complex rapid degradation signal.
Stop codon-proximal 3′UTR introns in vertebrates can elicit EJC-dependent Nonsense-Mediated mRNA Decay
Authors: Gangras Pooja , Gallagher Thomas L. , Patton Robert D. , Yi Zhongxia , Parthun Michael A. , Tietz Kiel T. , Deans Natalie C. , Bundschuh Ralf , Amacher Sharon L. , Singh Guramrit 
Published: June 2019

AbstractThe Exon Junction Complex (EJC) regulates many steps in post-transcriptional gene expression and is essential for cellular function and organismal development; however, EJC-regulated genes and genetic pathways during development remain largely unknown. To study EJC function during zebrafish development, we first established that zebrafish EJCs mainly bind ∼24 nucleotides upstream of exon-exon junctions, and are also detected at more distant non-canonical positions. We then generated mutations in two zebrafish EJC core genes, rbm8a and magoh, and observed that homozygous mutant embryos show paralysis, muscle disorganization, neural cell death, and motor neuron outgrowth defects. Coinciding with developmental defects, mRNAs subjected to Nonsense-Mediated mRNA Decay (NMD) due to translation termination ≥ 50 nts upstream of the last exon-exon junction are upregulated in EJC mutant embryos. Surprisingly, several transcripts containing 3′UTR introns (3′UI) < 50 nts downstream of a stop codon are also upregulated in EJC mutant embryos. These proximal 3′UI-containing transcripts are also upregulated in NMD-compromised zebrafish embryos, cultured human cells, and mouse embryonic stem cells. Loss of function of foxo3b, one of the upregulated proximal 3′UI-containing genes, partially rescues EJC mutant motor neuron outgrowth. In addition to foxo3b, 166 other genes contain a proximal 3′UI in zebrafish, mouse and humans, and these genes are enriched in nervous system development and RNA binding functions. A proximal 3′UI-containing 3′UTR from one of these genes, HNRNPD, is sufficient to reduce steady state transcript levels when fused to a β-globin reporter in HeLa cells. Overall, our work shows that genes with stop codon-proximal 3′UIs encode a new class of EJC-regulated NMD targets with critical roles during vertebrate development.
GDF15 and the beneficial actions of metformin in pre-diabetes
Authors: Coll Anthony P , Chen Michael , Taskar Pranali , Rimmington Debra , Patel Satish , Tadross John , Cimino Irene , Yang Ming , Welsh Paul , Virtue Samuel , Goldspink Deborah A. , Miedzybrodzka Emily , Tung Y. C. Loraine , Rodriguez-Cuenca Sergio , Tomaz Rute A. , Harding Heather P. , Melvin Audrey , Yeo Giles S.H. , Preiss David , Vidal-Puig Antonio , Vallier Ludovic , Ron David , Gribble Fiona M. , Reimann Frank , Sattar Naveed , Savage David B. , Allan Bernard B. , O’Rahilly Stephen 
Published: June 2019

SummaryMetformin, the world’s most prescribed anti-diabetic drug, is also effective in preventing Type 2 diabetes in people at high risk, by lowering body weight, fat mass and circulating insulin levels through mechanisms that are incompletely understood. Recent observational studies reporting the association of metformin use and circulating levels of GDF15 led us to hypothesize that GDF15, which signals through a specific receptor complex in the hindbrain to reduce body weight, might mediate these effects. We measured GDF15 in people without diabetes from a randomized placebo-controlled trial of metformin. Over 18 months, participants allocated metformin lost significant weight and levels of GDF15 were persistently elevated compared to placebo. The change in plasma GDF15 in this study correlated positively with weight loss. In wild-type mice, oral metformin increased circulating GDF15 with GDF15 expression increasing predominantly in the distal intestine and the kidney. Metformin prevented weight gain in response to high fat diet in wild-type mice but not in mice lacking GDF15 or its receptor GFRAL. In obese, high fat-fed mice, the effects of metformin to reduce body weight were reversed by a GFRAL antagonist antibody. Metformin had effects on both energy intake and energy expenditure that required GDF15. The insulin sensitising effects of metformin determined by insulin tolerance were abolished in mice lacking GDF15. Metformin significantly reduced fasting glucose and insulin levels in wild type but not in mice lacking GDF15. In summary, metformin increases the circulating levels of GDF15, which appears to be necessary for many of its actions as a metabolic chemopreventive agent.
Computational model demonstrates that Ndc80-associated proteins strengthen kinetochore-microtubule attachments in metaphase
Authors: Campbell Samuel , Amin Mohammed Abdullahel , Varma Dileep , Bidone Tamara Carla 
Published: June 2019

AbstractChromosome segregation is mediated by spindle microtubules that attach to kinetochore via dynamic protein complexes, such as Ndc80, Ska, Cdt1 and ch-TOG during mitotic metaphase. While experimental studies have previously shown that these proteins and protein complexes are all essential for maintaining a stable kinetochore-microtubule interface, their exact roles in this process remains elusive. In this study, we employed experimental and computational methods in order to characterize how these proteins can strengthen kMT attachments in both non load-bearing and load-bearing conditions, typical of prometaphase and metaphase, respectively. Immunofluorescence staining of Hela cells showed that the levels of Ska and Cdt1 significantly increase from prometaphase to metaphase. Our new computational model showed that, by incorporating binding and unbinding of each protein complex, coupled with a biased diffusion mechanism, the displacement of a possible complex formed by Ndc80-Ska-Cdt1 is significantly higher than that formed by Ndc80 alone or Ndc80-Ska. In addition, when we use Ndc80/ch-TOG in the model, rupture force and time of attachment of the kMT interface increases. These results support the hypothesis that Ndc80-associated proteins strengthen kMT attachments and that it is the interplay between kMT protein complexes in metaphase that ensures stable attachments.
Improved Sensitivity in Low-Input Proteomics using Micro-Pillar Array-based Chromatography
Authors: Stadlmann Johannes , Hudecz Otto , Krššáková Gabriela , Van Raemdonck Gert , Op De Beeck Jeff , Desmet Gert , Penninger Josef M. , Jacobs Paul , Mechtler Karl 
Published: June 2019

ABSTRACTCapitalizing on the massive increase in sample concentrations which are produced by extremely low elution volumes, nano-LC-ESI-MS/MS is currently one of the most sensitive analytical technologies for the comprehensive characterization of complex protein samples.However, despite tremendous technological improvements made in the production and the packing of monodisperse spherical particles for nano-flow HPLC, current state-of-the-art systems still suffer from limits in operation at the maximum potential of the technology.With the recent introduction of the µPAC system, which provides perfectly ordered micro-pillar array based chromatographic support materials, completely new chromatographic concepts for optimization towards the needs of ultra-sensitive proteomics become available.Here we report on a series of benchmarking experiments comparing the performance of a commercially available 50 cm micro-pillar array column to a widely used nano-flow HPLC column for the proteomics analysis of 10 ng tryptic HeLa cell digest.Comparative analysis of LC-MS/MS-data corroborated that micro-pillar array cartridges provide outstanding chromatographic performance, excellent retention time stability, increase sensitivity in the analysis of low-input proteomics samples, and thus repeatedly yielded almost twice as many unique peptide and unique protein group identifications when compared to conventional nano-flow HPLC columns.