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Nature Communications; Guan Y, Liang X et. al.
Aug 25th, 2021 - Genome-wide association studies (GWAS) have identified loci for kidney disease, but the causal variants, genes, and pathways remain unknown. Here we identify two kidney disease genes Dipeptidase 1 (DPEP1) and Charged Multivesicular Body Protein 1 A (CHMP1A) via the triangulation of kidney function GWAS, human kidney expression, and methylation quantitative trait loci. Using single-cell chromati...
https://doi.org/10.1038/s41467-021-25341-9 10.1016/j.cell.2018.03.035 10.1126/science.1096502 10.1073/pnas.1902651116 10.1016/j.cell.2015.06.053 10.1016/j.cell.2015.09.033 10.1038/nature11412 10.1016/j.cell.2017.07.029 10.1038/nrc2664 10.1038/bjc.2016.430 10.1016/j.ejca.2017.02.030 10.1038/nrd2926 10.1038/ncomms9501 10.1073/pnas.1323004111 10.1158/2159-8290.CD-12-0003 10.1016/j.ceb.2008.12.007 10.1073/pnas.0802655105 10.1073/pnas.0607899103 10.1158/1078-0432.CCR-14-2034 10.1158/1535-7163.MCT-14-0406 10.1158/1535-7163.MCT-13-0865 10.1126/science.aah6893 10.1002/cncr.29578 10.1126/scitranslmed.aaa4442 10.1016/j.ccr.2011.04.008 10.1158/1078-0432.CCR-18-0981 10.1056/NEJMoa1813904 10.1200/JCO.2017.72.7107 10.1038/nature07091 10.1016/j.ccell.2020.03.001 10.1016/j.cell.2014.08.016 10.1016/j.ccell.2014.11.008 10.1016/j.ccell.2014.11.007 10.1038/nature13948 10.1038/s41419-018-1025-8 10.1038/s41586-018-0343-4 10.1186/s13058-016-0697-1 10.1210/endo.137.10.8828504 10.1158/1078-0432.CCR-12-3072 10.1200/JCO.19.00368 10.1158/1078-0432.CCR-17-2260 10.1016/S1470-2045(17)30450-3 10.1158/1078-0432.CCR-13-0978 10.1158/1535-7163.MCT-11-0824-T 10.1200/JCO.18.01460 10.1016/S2352-3026(17)30019-4 10.1056/NEJMoa1315226 10.1016/j.cell.2014.08.017 10.1126/science.aah4307 10.1016/j.ccell.2020.06.005 10.1016/j.celrep.2013.11.020 10.1093/bioinformatics/bts635 10.1186/gb-2011-12-3-r22
Nature Communications; Mao N, Zhang Z et. al.
Aug 22nd, 2021 - Previous studies have suggested that PTEN loss is associated with p110β signaling dependency, leading to the clinical development of p110β-selective inhibitors. Here we use a panel pre-clinical models to reveal that PI3K isoform dependency is not governed by loss of PTEN and is impacted by feedback inhibition and concurrent PIK3CA/PIK3CB alterations. Furthermore, while pan-PI3K inhibition in PT...
Nature Communications; Arandjelovic S, Perry JSA et. al.
Aug 19th, 2021 - Osteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important 'signaling node' in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflam...
Nature Communications; Blaze J, Navickas A et. al.
Aug 15th, 2021 - Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2...
Nature Communications; Dagg RA, Zonderland G et. al.
Aug 15th, 2021 - BRCA1 or BRCA2 germline mutations predispose to breast, ovarian and other cancers. High-throughput sequencing of tumour genomes revealed that oncogene amplification and BRCA1/2 mutations are mutually exclusive in cancer, however the molecular mechanism underlying this incompatibility remains unknown. Here, we report that activation of β-catenin, an oncogene of the WNT signalling pathway, inhibi...
Nature Communications; Nilsson KH, Henning P et. al.
Aug 15th, 2021 - With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA an...
BMJ Case Reports; Hasan F, Gupta A et. al.
Aug 13th, 2021 - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterised by thrombocytopenia, microangiopathic haemolytic anaemia and microvascular thrombosis. Congenital TTP accounting for less than 5% of all TTP cases can have a late presentation in adulthood mostly triggered by predisposing factors such as infection, pregnancy and inflammation. We present a case of a 23-year-old...
The New England Journal of Medicine; Gurnari C, Rogers HJ
Aug 7th, 2021 - Copper Deficiency.|2021|Gurnari C,Rogers HJ,|etiology,pathology,deficiency,etiology,
BMJ Case Reports; Das D, Rathod A et. al.
Aug 7th, 2021 - Acrodermatitis enteropathica with ocular manifestations.|2021|Das D,Rathod A,Modaboyina S,Agrawal S,|diagnosis,etiology,deficiency,
Nature Communications; Chai RJ, Werner H et. al.
Aug 7th, 2021 - Mutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3-4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1's f...
Nature Communications; Ring SS, Cupovic J et. al.
Aug 7th, 2021 - The tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intratumoral treatment of mice with a recom...
Nature Communications; Li M, Li L et. al.
Aug 7th, 2021 - Gut microbiota deficient mice demonstrate accelerated glucose clearance. However, which tissues are responsible for the upregulated glucose uptake remains unresolved, with different studies suggesting that browning of white adipose tissue, or modulated hepatic gluconeogenesis, may be related to enhanced glucose clearance when the gut microbiota is absent. Here, we investigate glucose uptake in ...
Cancer Treatment Reviews; Trillo Aliaga P, Spada F et. al.
Aug 1st, 2021 - Temozolomide (TEM) is an active treatment in metastatic neuroendocrine tumors (NETs). Patients affected by glioblastoma multiforme or advanced melanoma treated with TEM who have deficiency of O6-methylguanine DNA methyltransferase (MGMT) have a better responses and survival. However, the predictive role of MGMT in patients with NETs treated with TEM is still debated. We conducted a systematic r...
The Lancet. Haematology; Braat S, Pasricha SR
Jul 31st, 2021 - Finding ferritin in the plateaus and valleys of iron deficiency.|2021|Braat S,Pasricha SR,|blood,diagnosis,blood,blood,analysis,blood,deficiency,
Nature Communications; Zhang X, Huang X et. al.
Jul 29th, 2021 - Despite the substantial impact of post-translational modifications on programmed cell death 1 ligand 1 (PD-L1), its importance in therapeutic resistance in pancreatic cancer remains poorly defined. Here, we demonstrate that never in mitosis gene A-related kinase 2 (NEK2) phosphorylates PD-L1 to maintain its stability, causing PD-L1-targeted pancreatic cancer immunotherapy to have poor efficacy....
Journal of Medical Case Reports; Sivashangar A, Gooneratne L et. al.
Jul 28th, 2021 - Erythrocyte pyruvate kinase is expressed under the control of the PKLR gene located on chromosome 1q21. Pyruvate kinase catalyzes the final steps of the glycolytic pathway and creates 50% of the red cell total adenosine triphosphate. Pyruvate kinase deficiency is the commonest glycolytic defect causing congenital non-spherocytic hemolytic anemia inherited in an autosomal recessive trait in whic...
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Human Genetics; Alsaif HS, Al Ali H et. al.
Jul 28th, 2021 - The purpose of this study is to describe a Mendelian disorder of DNA damage repair. Phenotypic delineation of two families, one new and one previously published, with overlapping dysmorphic and neurodevelopmental features was undertaken. Functional characterization of DNA damage repair in fibroblasts obtained from the index individuals in each of the two families was pursued. We present new evi...
Nature Communications; Launay A, Wu CJ et. al.
Jul 25th, 2021 - Zoonotic transfer of animal pathogens to human hosts can generate novel agents, but the genetic events following such host jumps are not well studied. Here we characterize the mechanisms driving adaptive evolution of the emerging zoonotic pathogen Bordetella hinzii in a patient with interleukin-12 receptor β1 deficiency. Genomic sequencing of 24 B. hinzii isolates cultured from blood and stool ...
Nature Communications; Perez-Frances M, van Gurp L et. al.
Jul 24th, 2021 - The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by β-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signatur...
Nature Communications; Chao ML, Luo S et. al.
Jul 24th, 2021 - Atherosclerosis-associated cardiovascular disease is one of the main causes of death and disability among patients with diabetes mellitus. However, little is known about the impact of S-nitrosylation in diabetes-accelerated atherosclerosis. Here, we show increased levels of S-nitrosylation of guanine nucleotide-binding protein G(i) subunit alpha-2 (SNO-GNAI2) at Cysteine 66 in coronary artery s...