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Objective: Clinical and genetic heterogeneities make diagnosis of limb‐girdle muscular dystrophy (LGMD) and other overlapping disorders of muscle weakness complicated and expensive. We aimed to develop a comprehensive next generation sequence‐based multi‐gene panel ("The Lantern Focused Neuromuscular Panel") to detect both sequence variants and copy number variants in one assay. Methods: Patients with clinical diagnosis of LGMD or other overlapping muscular dystrophies in the United States were tested by PerkinElmer Genomics in 2018–2021 via "The Lantern Project," a sponsored diagnostic testing program. Sixty‐six genes related to LGMD subtypes‐ and other myopathies were investigated. Main outcomes were diagnostic yield, gene‐variant spectrum, and LGMD subtypes' prevalence. Results: Molecular diagnosis was established in 19.6% (1266) of 6473 cases. Major genes contributing to LGMD were identified including CAPN3 (5.4%, 68), DYSF (4.0%, 51), GAA (3.7%, 47), ANO5 (3.6%, 45), and FKRP (2.7%, 34). Genes of other overlapping MD subtypes identified included PABPN1 (10.5%, 133), VCP (2.2%, 28), MYOT (1.2% 15), LDB3 (1.0%, 13), COL6A1 (1.5%, 19), FLNC (1.1%, 14), and DNAJB6 (0.8%, 10). Different sizes of copy number variants including single exon, multi‐exon, and whole genes were identified in 7.5% (95) cases in genes including DMD, EMD, CAPN3, ANO5, SGCG, COL6A2, DOK7, and LAMA2. Interpretation: "The Lantern Focused Neuromuscular Panel" enables identification of LGMD subtypes and other myopathies with overlapping clinical features. Prevalence of some MD subtypes was higher than previously reported. Widespread deployment of this comprehensive NGS panel has the potential to ensure early, accurate diagnosis as well as re‐define MD epidemiology. [ABSTRACT FROM AUTHOR]

Oxygen levels range from 2% to 9% in vivo. Atmospheric O2 levels (21%) are known to induce cell proliferation defects and cellular senescence in primary cell cultures. However, the mechanistic basis of the deleterious effects of higher O2 levels is not fully understood. On the other hand, immortalized cells including cancer cell lines, which evade cellular senescence are normally cultured at 21% O2 and the effects of higher O2 on these cells are understudied. Here, we addressed this problem by culturing immortalized human bronchial epithelial (BEAS-2B) cells at ambient atmospheric, 21% O2 and lower, 10% O2. Our results show increased inflammatory response at 21% O2 but not at 10% O2. We found higher RelA binding at the NF-κB1/RelA target gene promoters as well as upregulation of several pro-inflammatory cytokines in cells cultured at 21% O2. RelA knockdown prevented the upregulation of the pro-inflammatory cytokines at 21% O2, suggesting NF-κB1/RelA as a major mediator of inflammatory response in cells cultured at 21% O2. Interestingly, unlike the 21% O2 cultured cells, exposure of 10% O2 cultured cells to H2O2 did not elicit inflammatory response, suggesting increased ability to tolerate oxidative stress in cells cultured at lower O2 levels. J. Cell. Physiol. 231: 1611-1620, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Glycoproteins play a critical role in host-pathogen interactions, antigenicity, and virulence determination, and are therefore, considered as potential drug targets. The cell wall of Mycobacterium tuberculosis ( Mtb), the causative agent of tuberculosis (TB), dominantly contains sugars and lipids. Despite the efforts taken by the World Health Organization to reduce the incidence rate, the prevalence of TB is increasing in certain regions. This is mainly attributed to the emergence of multidrug-resistant bacteria. Factors that contribute to Mtb virulence and antigenicity remain elusive. However, several studies have shown that sugars and lipids are mainly responsible for Mtb pathogenesis and resistance to numerous drugs. This review gives insight into the role of glycoproteins in mycobacterium pathogenesis, disease development, and its implications in drug development. [ABSTRACT FROM AUTHOR]