bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjögren syndrome
Authors: Chen T -H , Lai T -Y , Wang Y -H , Chiou J -Y , Hung Y -M , Wei J C -C 
Published: June 2019

Abstract

Objectives
To determine whether taking hydroxychloroquine (HCQ) could prevent the development of new-onset diabetes mellitus (DM) among patients with Sjögren syndrome (SS).

Methods
This is a nationwide, population-based, retrospective cohort study utilizing the Taiwan National Health Insurance Research Database (NHIRD). Data were collected from 1 January 1999, through 31 December 2013, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. In total, 7774 patients newly diagnosed with SS by at least three outpatient visits or one inpatient admission were selected from the NHIRD as participants. Patients who had previously been diagnosed with DM and whose follow-up durations shorter than 90 days were excluded. HCQ exposure group includes patients who had been diagnosed with SS no longer than 180 days previously, and had been prescribed HCQ for the first time for at least 90 days. The diagnosis of DM was defined as at least two outpatient visits or one inpatient admission with anti-diabetic medication prescription.

Results
Patients with SS treated with HCQ had a significantly lower cumulative incidence of new-onset DM than those not treated with HCQ (adjusted hazard ratio: 0.51, 95% confidence interval: 0.28–0.96, P < 0.05). HCQ use for 3 years or more had favorable protective effects (adjusted hazard ratio: 0.22, CI: 0.05–0.92).

Conclusions
HCQ reduced the incidence of DM in a time and dose-dependent manner. Patients with SS who had taken HCQ for 3 years or more exhibited significant protective effects against developing new-onset DM.
Early Stem Cell Aging in the Mature Brain
Authors: Ibrayeva Albina , Bay Maxwell , Pu Elbert , Jörg David , Peng Lei , Jun Heechul , Zhang Naibo , Aaron Daniel , Lin Congrui , Resler Galen , Hidalgo Axel , Jang Mi-Hyeon , Simons Benjamin D. , Bonaguidi Michael A. 
Published: June 2019

SUMMARYStem cell dysfunction drives many age-related disorders. Identifying mechanisms that initially compromise stem cell function represent early targets to enhance stem cell behavior later in life. Here, we pinpoint multiple factors that disrupt neural stem cells (NSC) in the adult hippocampus. We find that NSCs exhibit asynchronous maintenance by identifying short-term (ST-NSC) and intermediate-term NSCs (IT-NSCs). ST-NSC divide rapidly to generate neurons and deplete in the young brain. Meanwhile, multipotent IT-NSCs persist for months, but are pushed out of homeostasis by lengthening quiescence. Single cell transcriptome analysis of deep NSC quiescence revealed several hallmarks of biological aging in the mature brain and identified tyrosine-protein kinase Abl1 as an NSC pro-aging factor. Treatment with the Abl-inhibitor Imatinib increased NSC proliferation without impairing NSC maintenance in the middle-aged brain. Further intersectional analysis of mature NSC with old epidermal, hematopoietic and muscle stem cell transcriptomes identified consensus changes in stem cell aging. Our study elucidates multiple origins of adult neurogenesis decline and reveals that hippocampal NSCs are particularly vulnerable to a shared stem cell aging signature.
Microbial Nitrogen Metabolism in Chloraminated Drinking Water Reservoirs
Authors: Potgieter Sarah C , Dai Zihan , Venter Stefanus N , Sigudu Makhosazana , Pinto Ameet J 
Published: June 2019

AbstractNitrification is a common concern in chloraminated drinking water distribution systems. The addition of ammonia promotes the growth of nitrifying organisms, causing the depletion of chloramine residuals and resulting in operational problems for many drinking water utilities. Therefore, a comprehensive understanding of the microbially mediated processes behind nitrogen metabolism together with chemical water quality data, may allow water utilities to better address the undesirable effects caused by nitrification. In this study, a metagenomic approach was applied to characterise the microbial nitrogen metabolism within chloraminated drinking water reservoirs. Samples from two geographically separated but connected chloraminated reservoirs within the same drinking water distribution system (DWDS) were collected within a 2-year sampling campaign. Spatial changes in the nitrogen compounds (ammonium (NH4+), nitrites (NO2−) and nitrates (NO3−)) across the DWDS were observed, where nitrate concentrations increased as the distance from the site of chloramination increased. The observed dominance ofNitrosomonasandNitrospira-like bacteria, together with the changes in the concentration of nitrogen species, suggests that these bacteria play a significant role in contributing to varying stages of nitrification in both reservoirs. Functionally annotated protein sequences were mined for the genes associated with nitrogen metabolism and the community gene catalogue contained mostly genes involved in nitrification, nitrate and nitrite reduction and nitric oxide reduction. Furthermore, based on the construction of Metagenome Assembled Genomes (MAGs), a highly diverse assemblage of bacteria (i.e., predominatelyAlpha- andBetaproteobacteriain this study) was observed among the draft genomes. Specifically, 5 MAGs showed high coverage across all samples including twoNitrosomonas, Nitrospira, Sphingomonasand aRhizobiales-like MAGs. The role of these MAGs in nitrogen metabolism revealed that the fate nitrate may be linked to changes in ammonia concentrations, that is, when ammonia concentrations are low, nitrate may be assimilated back to ammonia for growth. Alternatively, nitrate may be reduced to nitric oxide and potentially used in the regulation of biofilm formation. Therefore, this study provides insight into the genetic network behind microbially mediated nitrogen metabolism and together with the water chemistry data improves our understanding nitrification in chloraminated DWDSs.
Nationwide prediction of type 2 diabetes comorbidities
Authors: Dworzynski Piotr , Aasbrenn Martin , Rostgaard Klaus , Melbye Mads , Gerds Thomas Alexander , Hjalgrim Henrik , Pers Tune H 
Published: June 2019

ABSTRACTIdentification of individuals at risk of developing disease comorbidities represents an important task in tackling the growing personal and societal burdens associated with chronic diseases. We employed machine learning techniques to investigate to what extent data from longitudinal, nationwide Danish health registers can be used to predict individuals at high risk of developing type 2 diabetes (T2D) comorbidities. Based on register data spanning hospitalizations, drug prescriptions and contacts with primary care contractors from >200,000 individuals newly diagnosed with T2D, we used logistic regression-, random forest- and gradient boosting models to predict five-year risk of heart failure (HF), myocardial infarction (MI), stroke (ST), cardiovascular disease (CVD) and chronic kidney disease (CKD). For HF, MI, CVD, and CKD, register-based models outperformed a reference model leveraging canonical individual characteristics by achieving area under the receiver operating characteristic curve improvements of 0.06, 0.03, 0.06, and 0.07, respectively. The top 1,000 patients predicted to be at highest risk exhibited observed incidence ratios exceeding 4.99, 3.52, 2.92 and 4.71 respectively. In summary, prediction of T2D comorbidities utilizing Danish registers led to consistent albeit modest performance improvements over reference models, suggesting that register data could be leveraged to systematically identify individuals at risk of developing disease comorbidities.
Two distinct feedback codes in V1 for ‘real’ and ‘imaginary’ internal experiences
Authors: Bergmann Johanna , Morgan Andrew T. , Muckli Lars 
Published: June 2019

AbstractVisual illusions and visual imagery are conscious sensory events that lack a corresponding physical input. But while everyday mental imagery feels distinct from incoming stimulus input, visual illusions, like hallucinations, are under limited volitional control and appear indistinguishable from physical reality. Illusions are thought to arise from lower-level processes within sensory cortices. In contrast, imagery involves a wide network of brain areas that recruit early visual cortices for the sensory representation of the imagined stimulus. Here, we combine laminar fMRI brain imaging with psychophysical methods and multivariate pattern analysis to investigate in human participants how seemingly ‘real’ and imaginary non-physical experiences are processed in primary visual cortex (V1). We find that the content of mental imagery is only decodable in deep layers, whereas illusory content is only decodable at superficial depths. This suggests that feedback to the different layers may serve distinct functions: low-level feedback to superficial layers might be responsible for shaping perception-like experiences, while deep-layer feedback might serve the formation of a more malleable ‘inner’ world, separate from ongoing perception.
Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases
Authors: Mohanty Priyesh , Rashmi  , Habibullah Batul Ismail , G S Arun , Das Ranabir 
Published: June 2019

AbstractThe deamidase OspI from enteric bacteriaShigella flexnerideamidates a glutamine residue in the host ubiquitin-conjugating enzyme UBC13 and converts it to glutamate (Q100E). Consequently, its polyubiquitination activity in complex with the RING-finger ubiquitin ligase TRAF6 and the downstream NF-κB inflammatory response is inactivated. The precise role of deamidation in inactivating the UBC13/TRAF6 complex is unknown. We report that deamidation inhibits the interaction between UBC13 and TRAF6 RING-domain (TRAF6RING) by perturbing both the native and transient interactions. Deamidation creates a new intramolecular salt-bridge in UBC13 that competes with a critical intermolecular salt-bridge at the native UBC13/TRAF6RINGinterface. Moreover, the salt-bridge competition prevents transient interactions necessary to form a typical UBC13/RING complex. Repulsion between E100 and the negatively charged surface of RING also prevents transient interactions in the UBC13/RING complex. Our findings highlight a mechanism where a post-translational modification perturbs the conformation and stability of transient complexes to inhibit protein-protein association.
Sophisticated suction organs from insects living in raging torrents: Morphology and ultrastructure of the attachment devices of net-winged midge larvae (Diptera: Blephariceridae)
Authors: Kang Victor , Johnston Richard , van de Kamp Thomas , Faragó Tomáš , Federle Walter 
Published: June 2019

2.AbstractSuction organs provide powerful yet dynamic attachments for many aquatic animals, including octopus, squid, remora, and clingfish. While the functional morphology of suction organs from various cephalopods and fishes has been investigated in detail, there are only few studies on such attachment devices in insects. Here we characterise the morphology, ultrastructure, andin vivomovements of the suction attachment organs of net-winged midge larvae (genusLiponeura) – aquatic insects that live on rocks in rapid alpine waterways where flow rates can reach 3 m s-1– using scanning electron microscopy, laser confocal scanning microscopy, and X-ray computed micro-tomography (micro-CT). We identified structural adaptations important for the function of the suction attachment organs fromL. cinerascensandL. cordata. First, a dense array of spine-like microtrichia covering each suction disc comes into contact with the substrate upon attachment. Similar hairy structures have been found on the contact zones of suction organs from octopus, clingfish, and remora fish. These structures are thought to contribute to the seal and to provide increased shear force resistance in high-drag environments. Second, specialised rim microtrichia at the suction disc periphery form a continuous ring in close contact with a surface and may serve as a seal on a variety of surfaces. Third, a V-shaped cut on the suction disc (the V-notch) is actively peeled open via two cuticular apodemes inserting into its flanks. The apodemes are attached to dedicated V-notch opening muscles, thereby providing a unique detachment mechanism. The complex cuticular design of the suction organs, along with specialised muscles that attach to them, allows blepharicerid larvae to generate powerful attachments which can withstand strong hydrodynamic forces and quickly detach for locomotion. Our findings could be applied to bio-inspired attachment devices that perform well on a wide range of surfaces.
A proteogenomic resource enabling integrated analysis ofListeriagenotype-proteotype-phenotype relationships
Authors: Varadarajan Adithi R. , Pavlou Maria P. , Goetze Sandra , Grosboillot Virginie , Shen Yang , Loessner Martin J. , Ahrens Christian H. , Wollscheid Bernd 
Published: June 2019

AbstractListeria monocytogenesis an opportunistic foodborne pathogen responsible for listeriosis, a potentially fatal foodborne disease. Many differentListeriastrains and serotypes exist, but a proteogenomic resource that bridges the gap in our molecular understanding of the relationships between theListeriagenotypes and phenotypes via proteotypes is still missing. Here we devised a next-generation proteogenomics strategy that enables the community to rapidly proteotypeListeriastrains and relate this information back to the genotype. Based on sequencing andde novoassembly of the two most commonly usedListeriamodel strains, EGD-e and ScottA, we established two comprehensiveListeriaproteogenomic databases. A genome comparison established core- and strain-specific genes potentially responsible for virulence differences. Next, we established a DIA/SWATH-based proteotyping strategy, including a new and robust sample preparation workflow, that enables the reproducible, sensitive, and relative quantitative measurement ofListeriaproteotypes. This reusable and publically available DIA/SWATH library covers 70% of open reading frames ofListeriaand represents the most extensive spectral library forListeriaproteotype analysis to date. We used these two new resources to investigate theListeriaproteotype in states mimicking the upper gastrointestinal passage. Exposure ofListeriato bile salts at 37 °C, which simulates conditions encountered in the duodenum, showed significant proteotype perturbations including an increase of FlaA, the structural protein of flagella. Given thatListeriais known to lose its flagella above 30 °C, this was an unexpected finding. The formation of flagella, which might have implications on infectivity, was validated by parallel reaction monitoring and light and scanning electron microscopy.flaAtranscript levels were not significantly different with and without exposure to bile salts at 37 °C, suggesting regulation at the post-transcriptional level. Together, these analyses provide a comprehensive proteogenomic resource and toolbox for theListeriacommunity enabling the analysis ofListeriagenotype-proteotype-phenotype relationships.
Phylogenetic and structural diversity of aromatically dense pili from environmental metagenomes
Authors: Bray M. S. , Wu J. , Padilla C.C. , Stewart F. J. , Fowle D. A. , Henny C. , Simister R. L. , Thompson K. J. , Crowe S. A. , Glass J. B. 
Published: June 2019

SummaryElectroactive type IV pili, or e-pili, are used by some microbial species for extracellular electron transfer. Recent studies suggest that e-pili may be more phylogenetically and structurally diverse than previously assumed. Here, we used updated aromatic density thresholds (≥9.8% aromatic amino acids, ≤22-aa aromatic gaps, and aromatic amino acids at residues 1, 24, 27, 50 and/or 51, and 32 and/or 57) to search for putative e-pilin genes in metagenomes from diverse ecosystems with active microbial metal cycling. Environmental putative e-pilins were diverse in length and phylogeny, and included truncated e-pilins inGeobacterspp., as well as longer putative e-pilins in Fe(II)-oxidizingBetaproteobacteriaandZetaproteobacteria.Originality and SignificanceElectroactive pili (e-pili) are used by microorganisms to respire solid metals in their environment through extracellular electron transfer. Thus, e-pili enable microbes to occupy specific environmental niches. Additionally, e-pili have important potential for biotechnological applications. Currently the repertoire of known e-pili is small, and their environmental distribution is largely unknown. Using sequence analysis, we identified numerous genes encoding putative e-pili from diverse anoxic, metal-rich ecosystems. Our results expand the diversity of putative e-pili in environments where metal oxides may be important electron acceptors for microbial respiration.
Stress Resets Transgenerational Small RNA Inheritance
Authors: Houri-Ze’evi Leah , Teichman Guy , Gingold Hila , Rechavi Oded 
Published: June 2019

AbstractTransgenerational inheritance of small RNAs is challenging basic concepts of heredity and achieving control over such responses is of great interest. InC. elegansnematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments and distinguish self from non-self genes. Inheritance of small RNAs is regulated by dedicated machinery and carryover of aberrant heritable small RNA responses was shown to be maladaptive and to induce sterility. Here we show that various types of stress (starvation, high temperatures, and high osmolarity) but not non-stressful changes in cultivation conditions, lead to resetting of small RNA inheritance. We found that stress leads to a genome-wide reduction in heritable small RNA levels and that mutants defective in different stress pathways exhibit irregular RNAi inheritance dynamics. Moreover, we discovered that resetting of heritable RNAi is orchestrated by MAPK pathway factors, the transcription factor SKN-1, and the MET-2 methyltransferase. Termination of small RNA inheritance, and the fact that this process depends on stress, could protect from run-on of environment-irrelevant heritable gene regulation.
Early-Stage Ocular Hypertension Alters Retinal Ganglion Cell Synaptic Transmission in the Visual Thalamus
Authors: Bhandari Ashish , Smith Jennie C. , Zhang Yang , Reid Lisa , Goeser Toni , Fan Shan , Ghate Deepta , Hook Matthew J. Van 
Published: June 2019

AbstractAxonopathy is a hallmark of many neurodegenerative diseases including glaucoma, where elevated intraocular pressure (ocular hypertension, OHT) stresses retinal ganglion cell (RGC) axons as they exit the eye and form the optic nerve. OHT causes early changes in the optic nerve such as axon atrophy, transport inhibition, and gliosis. Importantly, many of these changes appear to occur prior to irreversible neuronal loss, making them promising points for early diagnosis of glaucoma. It is unknown whether OHT has similarly early effects on the function of RGC output to the brain. To test this possibility, we elevated eye pressure in mice by anterior chamber injection of polystyrene microbeads. 5 weeks post-injection, bead-injected eyes showed a modest RGC loss in the peripheral retina, as evidenced by RBPMS antibody staining. Additionally, we observed reduced dendritic complexity and lower spontaneous spike rate of On-αRGCs, targeted for patch clamp recording and dye filling using aOpn4-cre reporter mouse line. To determine the influence of OHT on retinal projections to the brain, we expressed Channelrhodopsin-2 (ChR2) in melanopsin-expressing retinal ganglion cells by crossing theOpn4-cre mouse line with a ChR2-reporter mouse line and recorded post-synaptic responses in thalamocortical relay neurons in the dorsal lateral geniculate nucleus (dLGN) of the thalamus evoked by stimulation with 460 nm light. The use of aOpn4-cre reporter system allowed for expression of ChR2 in a narrow subset of RGCs responsible for image-forming vision in mice. Five weeks following OHT induction, paired pulse and high-frequency stimulus train experiments revealed that presynaptic vesicle release probability at retinogeniculate synapses was elevated. Additionally, miniature synaptic current frequency was slightly reduced in brain slices from OHT mice and proximal dendrites of post-synaptic dLGN relay neurons, assessed using a Sholl analysis, showed a reduced complexity. Strikingly, these changes occurred prior to major loss of RGCs labeled with theOpn4-Cre mouse, as indicated by immunofluorescence staining of ChR2-expressing retinal neurons. Thus, OHT leads to pre- and post-synaptic functional and structural changes at retinogeniculate synapses. Along with RGC dendritic remodeling and optic nerve transport changes, these retinogeniculate synaptic changes are among the earliest signs of glaucoma.
Cohort profile: The LipidCardio Study - Role of Lipoproteins in Cardiovascular Disease
Authors: König Maximilian , Joshi Samita , Leistner David M. , Landmesser Ulf , Sinning David , Steinhagen-Thiessen Elisabeth , Demuth Ilja 
Published: June 2019

AbstractPurposeThe LipidCardio Study was established for in-depth analyses of cardiovascular risk factors, providing well-defined cardiovascular and metabolic phenotypes. Particularly the role of lipoproteins in the pathobiological process and treatment of cardiovascular disease will be a main focus.Participants1.005 individuals aged 21 years and older undergoing cardiac catheterization during 17 months at a tertiary academic cardiology center were enrolled. The baseline data set contains detailed phenotyping, broad biochemical parameters, genetic data, but also standardized personal and family history, a screening test for cognitive impairment, pulse wave analysis and measurements of hand grip strength, amongst others. Blood samples were stored in a biobank for future analyses.Findings to dateThe mean age of the participants at enrolment was 70.9±11.1 years (70% male). Coronary angiography provided evidence of obstructive coronary artery disease (CAD) in 69.9% of participants. Those with evidence of CAD were significantly more likely to be male, inactive, diabetic and with a family history of cardiovascular disease than participants without CAD.20% of patients had lipoprotein(a) [Lp(a)] concentrations above 106.9 nmol/L (fifth quintile). These patients had significantly increased odds of obstructive CAD compared to participants in quintiles 1-4 (OR 1.70, 95% CI 1.17 to 2.48, p=0.005). There was reasonable evidence that with increasing severity of CAD the odds of having elevated Lp(a) increased. We were able to replicate the established strong association between specified single nucleotide polymorphisms (SNPs) in the LPA gene (rs10455872, rs3798220 and rs186696265) and the APOE gene (rs7412), and the concentration of Lp(a), validating our phenotype database and biobank.Future plansMortality information will be obtained in two-year intervals. Follow-up phone interviews will be conducted at 3, and 6 years after enrolment. We seek to cooperate with other researchers in the field, e.g. by sharing data and biobank samples.Registrationnot applicable, purely observational study