Displaying publications 81 - 100 of 289 in total

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  1. Distribution and assessment of heavy metal contents in surface sediments of the western Sunda Shelf
    Zhang H, Liu S, Wu K, Cui J, Zhu A, Zhang Y, et al.
    Mar Pollut Bull, 2021 Jul;168:112433.
    PMID: 33962084 DOI: 10.1016/j.marpolbul.2021.112433
    The heavy metal contents (Cr, Cu, Zn, Cd, Pb, Hg, and As) of 88 surface sediment samples from the western Sunda Shelf were analyzed to determine their spatial distribution patterns and contamination status. The results demonstrated that high enrichment regions of heavy metals were focused in the Kelantan, Pahang, and Ambat river estuaries, and deep water regions of the study area. These high enrichment regions were mainly controlled by riverine inputs and their hydrodynamic conditions. The enrichment factor (EF), geoaccumulation index (Igeo), and potential ecological risk index (PERI) were used to assess heavy metal accumulation. The results indicated that the study area was not significantly contaminated overall at the time of the study; however, Cd, As, and Hg were at levels corresponding to moderate contamination at many stations located in the Pahang River estuary, Kelantan River estuary, and north-eastern region of the study area, primarily because of anthropogenic activities.
  2. Ameliorative effect of Albizia chinensis synthesized ZnO-NPs on Mycoplasma pneumoniae infected pneumonia mice model
    Yu L, Lu M, Zhang W, Alarfaj AA, Hirad AH, Zhang H
    Microb Pathog, 2020 Apr;141:103960.
    PMID: 31953224 DOI: 10.1016/j.micpath.2019.103960
    BACKGROUND: Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) among the children and adults that results upper and lower respiratory tract infections.

    OBJECTIVE: This study was aimed to inspect the ameliorative action of A. chinensis synthesized ZnONPs against M. pneumoniae infected pneumonia mice model.

    MATERIALS AND METHODS: ZnO NPs was synthesized from Albizia chinensis bark extract and characterized by UV-Vis spectroscopy, Fourier Transform Infrared (FTIR), Transmission Electron Microscopy (TEM), energy dispersive X-ray (EDX) and atomic force microscope (AFM) analyses. The antibacterial effectual of synthesized ZnONPs were examined against clinical pathogens. The pneumonia was induced to BALB/c mice via injecting the M. pneumoniae and treated with synthesized ZnONPs, followed by the total protein content, total cell counts and inflammatory mediators level was assessed in the BALF of experimental animals. The Histopathological investigation was done in the lung tissues of test animals.

    RESULTS: The outcomes of this work revealed that the formulated ZnONPs was quasi-spherical, radial and cylindrical; the size was identified as 116.5 ± 27.45 nm in diameter. The in vitro antimicrobial potential of formulated ZnO-NPs displayed noticeable inhibitory capacity against the tested fungal and bacterial strains. The administration of synthesized ZnO-NPs in MP infected mice model has significantly reduced the levels of total protein, inflammatory cells, inflammatory cytokines such as IL-1, IL-6, IL-8, tumour necrosis factor-alpha (TNF-a) and transforming growth factor (TGF). Besides, the histopathological examination of MP infected mice lung tissue showed the cellular arrangements were effectively retained after administration of synthesized ZnO-NPs.

    CONCLUSION: In conclusion, synthesized ZnO-NPs alleviate pneumonia progression via reducing the level of inflammatory cytokines and inflammatory cells in MP infected mice model.

  3. Fulltext Shewanella phage encoding a putative anti-CRISPR-like gene represents a novel potential viral family
    Wang H, Zheng K, Wang M, Ma K, Ren L, Guo R, et al.
    Microbiol Spectr, 2024 Feb 06;12(2):e0336723.
    PMID: 38214523 DOI: 10.1128/spectrum.03367-23
    Shewanella is a prevalent bacterial genus in deep-sea environments including marine sediments, exhibiting diverse metabolic capabilities that indicate its significant contributions to the marine biogeochemical cycles. However, only a few Shewanella phages were isolated and deposited in the NCBI database. In this study, we report the isolation and characterization of a novel Shewanella phage, vB_SbaS_Y11, that infects Shewanella KR11 and was isolated from the sewage in Qingdao, China. Transmission electron microscopy revealed that vB_SbaS_Y11 has an icosahedral head and a long tail. The genome of vB_SbaS_Y11 is a linear, double-stranded DNA with a length of 62,799 bp and a G+C content of 46.9%, encoding 71 putative open reading frames. No tRNA genes or integrase-related feature genes were identified. An uncharacterized anti-CRISPR AcrVA2 gene was detected in its genome. Phylogenetic analysis based on the amino acid sequences of whole genomes and comparative genomic analyses indicate that vB_SbaS_Y11 has a novel genomic architecture and shares low similarity to Pseudomonas virus H66 and Pseudomonas phage F116. vB_SbaS_Y11 represents a potential new family-level virus cluster with eight metagenomic assembled viral genomes named Ranviridae.IMPORTANCEThe Gram-negative Shewanella bacterial genus currently includes about 80 species of mostly aquatic Gammaproteobacteria, which were isolated around the globe in a multitude of environments, such as freshwater, seawater, coastal sediments, and the deepest trenches. Here, we present a Shewanella phage vB_SbaS_Y11 that contains an uncharacterized anti-CRISPR AcrVA2 gene and belongs to a potential virus family, Ranviridae. This study will enhance the knowledge about the genome, diversity, taxonomic classification, and global distribution of Shewanella phage populations.
  4. Fulltext All-Optical Modulation Technology Based on 2D Layered Materials
    Yang H, Wang Y, Tiu ZC, Tan SJ, Yuan L, Zhang H
    Micromachines (Basel), 2022 Jan 07;13(1).
    PMID: 35056256 DOI: 10.3390/mi13010092
    In the advancement of photonics technologies, all-optical systems are highly demanded in ultrafast photonics, signal processing, optical sensing and optical communication systems. All-optical devices are the core elements to realize the next generation of photonics integration system and optical interconnection. Thus, the exploration of new optoelectronics materials that exhibit different optical properties is a highlighted research direction. The emerging two-dimensional (2D) materials such as graphene, black phosphorus (BP), transition metal dichalcogenides (TMDs) and MXene have proved great potential in the evolution of photonics technologies. The optical properties of 2D materials comprising the energy bandgap, third-order nonlinearity, nonlinear absorption and thermo-optics coefficient can be tailored for different optical applications. Over the past decade, the explorations of 2D materials in photonics applications have extended to all-optical modulators, all-optical switches, an all-optical wavelength converter, covering the visible, near-infrared and Terahertz wavelength range. Herein, we review different types of 2D materials, their fabrication processes and optical properties. In addition, we also summarize the recent advances of all-optical modulation based on 2D materials. Finally, we conclude on the perspectives on and challenges of the future development of the 2D material-based all-optical devices.
  5. Precessing jet nozzle connecting to a spinning black hole in M87
    Cui Y, Hada K, Kawashima T, Kino M, Lin W, Mizuno Y, et al.
    Nature, 2023 Sep;621(7980):711-715.
    PMID: 37758892 DOI: 10.1038/s41586-023-06479-6
    The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.
  6. Fulltext High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry
    Sun C, Molineros JE, Looger LL, Zhou XJ, Kim K, Okada Y, et al.
    Nat Genet, 2016 Mar;48(3):323-30.
    PMID: 26808113 DOI: 10.1038/ng.3496
    Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.
  7. Fulltext Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
    Zhang H, Ahearn TU, Lecarpentier J, Barnes D, Beesley J, Qi G, et al.
    Nat Genet, 2020 06;52(6):572-581.
    PMID: 32424353 DOI: 10.1038/s41588-020-0609-2
    Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P 
  8. "Mild'' Hypoxic-Ischaemic Encephalopathy and Therapeutic Hypothermia: A Survey of Clinical Practice and Opinion from 35 Countries
    Singla M, Chalak L, Kumar K, Hayakawa M, Mehta S, Neoh SH, et al.
    Neonatology, 2022;119(6):712-718.
    PMID: 36202069 DOI: 10.1159/000526404
    INTRODUCTION: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE).

    METHODS: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries.

    RESULTS: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH.

    CONCLUSIONS: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported.

  9. Probiotic consumption relieved human stress and anxiety symptoms possibly via modulating the neuroactive potential of the gut microbiota
    Ma T, Jin H, Kwok LY, Sun Z, Liong MT, Zhang H
    Neurobiol Stress, 2021 May;14:100294.
    PMID: 33511258 DOI: 10.1016/j.ynstr.2021.100294
    Stress has been shown to disturb the balance of human intestinal microbiota and subsequently causes mental health problems like anxiety and depression. Our previous study showed that ingesting the probiotic strain, Lactobacillus (L.) plantarum P-8, for 12 weeks could alleviate stress and anxiety of stressed adults. The current study was a follow-up work aiming to investigate the functional role of the gut metagenomes in the observed beneficial effects. The fecal metagenomes of the probiotic (n = 43) and placebo (n = 36) receivers were analyzed in depth. The gut microbiomes of the placebo group at weeks 0 and 12 showed a significantly greater Aitchison distance (P 
  10. Renal Impairment and Risk of Acute Stroke: The INTERSTROKE Study
    Smyth A, Judge C, Wang X, Pare G, Rangarajan S, Canavan M, et al.
    Neuroepidemiology, 2021;55(3):206-215.
    PMID: 33951632 DOI: 10.1159/000515239
    BACKGROUND: Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association.

    AIMS: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations.

    METHODS: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke.

    RESULTS: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month).

    CONCLUSION: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.

  11. Fulltext Global Impact of COVID-19 on Stroke Care and IV Thrombolysis
    Nogueira RG, Qureshi MM, Abdalkader M, Martins SO, Yamagami H, Qiu Z, et al.
    Neurology, 2021 Jun 08;96(23):e2824-e2838.
    PMID: 33766997 DOI: 10.1212/WNL.0000000000011885
    OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

    METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

    RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

    CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

  12. Fulltext International expert consensus statement about methods and indications for keyhole microneurosurgery from International Society on Minimally Invasive Neurosurgery
    Lan Q, Sughrue M, Hopf NJ, Mori K, Park J, Andrade-Barazarte H, et al.
    Neurosurg Rev, 2021 02;44(1):1-17.
    PMID: 31754934 DOI: 10.1007/s10143-019-01188-z
  13. Correction: KSR1 regulates BRCA1 degradation and inhibits breast cancer growth
    Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, et al.
    Oncogene, 2021 May 04.
    PMID: 33947963 DOI: 10.1038/s41388-021-01794-6
  14. KSR1 regulates BRCA1 degradation and inhibits breast cancer growth
    Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, et al.
    Oncogene, 2015 Apr 16;34(16):2103-14.
    PMID: 24909178 DOI: 10.1038/onc.2014.129
    Kinase suppressor of Ras-1 (KSR1) facilitates signal transduction in Ras-dependent cancers, including pancreatic and lung carcinomas but its role in breast cancer has not been well studied. Here, we demonstrate for the first time it functions as a tumor suppressor in breast cancer in contrast to data in other tumors. Breast cancer patients (n>1000) with high KSR1 showed better disease-free and overall survival, results also supported by Oncomine analyses, microarray data (n=2878) and genomic data from paired tumor and cell-free DNA samples revealing loss of heterozygosity. KSR1 expression is associated with high breast cancer 1, early onset (BRCA1), high BRCA1-associated ring domain 1 (BARD1) and checkpoint kinase 1 (Chk1) levels. Phospho-profiling of major components of the canonical Ras-RAF-mitogen-activated protein kinases pathway showed no significant changes after KSR1 overexpression or silencing. Moreover, KSR1 stably transfected cells formed fewer and smaller size colonies compared to the parental ones, while in vivo mouse model also demonstrated that the growth of xenograft tumors overexpressing KSR1 was inhibited. The tumor suppressive action of KSR1 is BRCA1 dependent shown by 3D-matrigel and soft agar assays. KSR1 stabilizes BRCA1 protein levels by reducing BRCA1 ubiquitination through increasing BARD1 abundance. These data link these proteins in a continuum with clinical relevance and position KSR1 in the major oncoprotein pathways in breast tumorigenesis.
  15. Correction to: KSR1 regulates BRCA1 degradation and inhibits breast cancer growth
    Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, et al.
    Oncogene, 2021 May;40(19):3473.
    PMID: 33888869 DOI: 10.1038/s41388-021-01759-9
  16. Fulltext Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine Metabolism in Rats
    Mazlan M, Hamezah HS, Taridi NM, Jing Y, Liu P, Zhang H, et al.
    Oxid Med Cell Longev, 2017;2017:6019796.
    PMID: 29348790 DOI: 10.1155/2017/6019796
    Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF) on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.
  17. Fulltext Goji Berries as a Potential Natural Antioxidant Medicine: An Insight into Their Molecular Mechanisms of Action
    Ma ZF, Zhang H, Teh SS, Wang CW, Zhang Y, Hayford F, et al.
    Oxid Med Cell Longev, 2019;2019:2437397.
    PMID: 30728882 DOI: 10.1155/2019/2437397
    Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.
  18. Fulltext Dorsal root ganglia control nociceptive input to the central nervous system
    Hao H, Ramli R, Wang C, Liu C, Shah S, Mullen P, et al.
    PLoS Biol, 2023 Jan;21(1):e3001958.
    PMID: 36603052 DOI: 10.1371/journal.pbio.3001958
    Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.
  19. Fulltext Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians
    Molineros JE, Looger LL, Kim K, Okada Y, Terao C, Sun C, et al.
    PLoS Genet, 2019 04;15(4):e1008092.
    PMID: 31022184 DOI: 10.1371/journal.pgen.1008092
    Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology.
  20. Search for Narrow Resonances Decaying to Dijets in Proton-Proton Collisions at sqrt[s]=13  TeV
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Feb 19;116(7):071801.
    PMID: 26943527 DOI: 10.1103/PhysRevLett.116.071801
    A search for narrow resonances in proton-proton collisions at sqrt[s]=13  TeV is presented. The invariant mass distribution of the two leading jets is measured with the CMS detector using a data set corresponding to an integrated luminosity of 2.4  fb^{-1}. The highest observed dijet mass is 6.1 TeV. The distribution is smooth and no evidence for resonant particles is observed. Upper limits at 95% confidence level are set on the production cross section for narrow resonances with masses above 1.5 TeV. When interpreted in the context of specific models, the limits exclude string resonances with masses below 7.0 TeV, scalar diquarks below 6.0 TeV, axigluons and colorons below 5.1 TeV, excited quarks below 5.0 TeV, color-octet scalars below 3.1 TeV, and W^{'} bosons below 2.6 TeV. These results significantly extend previously published limits.
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