Hybrid dysgenesis is a sterility syndrome resulting from the mobilization of certain transposable elements in the Drosophila germline. Particularly extreme is the hybrid dysgenesis syndrome caused by P-element DNA transposons, in which dysgenic female ovaries often contain few or no germline cells. Those offspring that are produced from dysgenic germlines exhibit high rates of de novo mutation and recombination, implicating transposition-associated DNA damage as the cause of germline loss. However, how this loss occurs, in terms of the particular cellular response that is triggered (cell cycle arrest, senescence, or cell death) remains poorly understood. We demonstrate that two components of the DNA damage response, Checkpoint kinase 2 and its downstream target p53, determine the frequency of ovarian atrophy that is associated with P-element hybrid dysgenesis. We further show that p53 is strongly induced in the germline stem cells (GSCs) of dysgenic females, and is required for their maintenance. Our observations support the critical role for p53 in conferring tolerance of transposable element activity in stem cells.
The sternoclavicular joint (SCJ) is anatomically and clinically significant considering its proximity to important neuro-vascular structures like the subclavian vessels and the phrenic nerve. Infections of this joint masquerade multiple disorders, delay diagnosis and spread to the bone and deep tissues. There is no standardized workup and treatment protocol for sternoclavicular joint infections (SCJI) as defined in literature. Here, we review the existing literature to understand the current knowledge of the diagnosis and treatment of SCJI. We searched English publications in PubMed and included clinical trials, case reports, case series, retrospective cohort studies, literature and systematic reviews after excluding non-infectious etiology of SCJ pathologies. There are many risk factors for SCJI, such as immunocompromised status, intravenous drug use, trauma and arthropathies. But a large percentage of patients with disease have none of these risk factors. SCJIs can present with fever, joint swelling, immobility, and rarely with vocal cord palsy or dysphagia. While Staphylococcus aureus causes over 50% of SCJI cases, other pathogens such as Pseudomonas and Mycobacterium are frequently seen. When diagnosed early, the infection can be medically managed with antibiotics or joint aspirations. Most cases of SCJI, however, are diagnosed after extensive spread to soft tissue and bones requiring en-bloc resection with or without a muscle flap. Complications of undertreatment can range from simple abscess formation to mediastinitis, even sepsis. SCJIs are rare but serious infections prompting early detection and interventions. Most cases of SCJI treated adequately show complete resolution in months while retaining maximum functionality. Key features of proper healing include aggressive physiotherapy to prevent adhesive shoulder capsulitis and decreased range of motion.
Dysregulated alternative splicing (AS) that contributes to diabetes pathogenesis has been identified, but little is known about the RNA binding proteins (RBPs) involved. We have previously found that the RBP CELF1 is upregulated in the diabetic heart; however, it is unclear if CELF1 contributes to diabetes-induced AS changes. Utilizing genome wide approaches, we identified extensive changes in AS patterns in Type 1 diabetic (T1D) mouse hearts. We discovered that many aberrantly spliced genes in T1D hearts have CELF1 binding sites. CELF1-regulated AS affects key genes within signaling pathways relevant to diabetes pathogenesis. Disruption of CELF1 binding sites impairs AS regulation by CELF1. In sum, our results indicate that CELF1 target RNAs are aberrantly spliced in the T1D heart leading to abnormal gene expression. These discoveries pave the way for targeting RBPs and their RNA networks as novel therapies for cardiac complications of diabetes.
Background
Changes in the esophageal microbiome correlate with esophageal disease, but the effects of proton pump inhibitor (PPI) drugs are incompletely characterized. Our objective was to identify the effects of PPI use on the microbial community of the esophagus.
Methods
Mucosal biopsies of the distal esophagus were analyzed using a customized esophageal microbiome qPCR panel array (EMB). Patient demographics, use of PPIs, duration of use and dose were recorded.
Results
Fifty-eight patients were included. Mean age was 60.5 years. Ninety percent (52/58) of patients were on PPIs. Mean dose was 42.7 mg. Mean duration of use was 2.5 years. The use of PPIs led to a significant difference in absolute levels of only one organism, Actinomyces, in the entire array (p < 0.01). Among patients who used proton pump inhibitors, there was no significant association between dose and absolute levels of any organism. Similarly, there was no association between duration of use and absolute levels of any organism.
Conclusions
PPI use does not seem to cause significant changes in the distal esophageal microbial community. Future studies with larger sample sizes and esophageal pH testing should be performed to determine the level of acidity and its relationship to the microbial community.
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