Over 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammation, rectal bleeding, and dehydration. Interestingly, a widespread recommendation to IBD patients for avoidance of a flare period is "Don't Drink Alcohol" as recent work correlated alcohol consumption with increased GI symptoms in patients with IBD. Alcohol alone not only induces a systemic pro-inflammatory response, but can also be directly harmful to gut barrier integrity. However, how alcohol could result in the exacerbation of UC in both patients and murine models of colitis has yet to be elucidated. Therefore, we conducted a retrospective analysis of patients admitted for IBD with a documented history of alcohol use in conjunction with a newly developed mouse model of binge alcohol consumption following dextran sulfate sodium (DSS)-induced colitis. We found that alcohol negatively impacts clinical outcomes of patients with IBD, specifically increased intestinal infections, antibiotic injections, abdomen CT scans, and large intestine biopsies. Furthermore, in our mouse model of binge alcohol consumption following an induced colitis flare, we found alcohol exacerbates weight loss, clinical scores, colonic shortening and inflammation, and propensity to infection. These findings highlight alcohol's ability to potentiate symptoms and susceptibility to infection in UC and suggest alcohol as an underlying factor in perpetuating symptoms of IBD.
Telomeres are the nucleoprotein complexes at eukaryotic chromosomal ends. Telomeric DNA is synthesized by the ribonucleoprotein telomerase, which comprises a telomerase reverse transcriptase (TERT) and a telomerase RNA (TER). TER contains a template for telomeric DNA synthesis. Filamentous fungi possess extremely short and tightly regulated telomeres. Although TERT is well conserved between most organisms, TER is highly divergent and thus difficult to identify. In order to identify the TER sequence, we used the unusually long telomeric repeat sequence of Aspergillus oryzae together with reverse-transcription-PCR and identified a transcribed sequence that contains the potential template within a region predicted to be single stranded. We report the discovery of TERs from twelve other related filamentous fungi using comparative genomic analysis. These TERs exhibited strong conservation with the vertebrate template sequence, and two of these potentially use the identical template as humans. We demonstrate the existence of important processing elements required for the maturation of yeast TERs such as an Sm site, a 5′ splice site and a branch point, within the newly identified TER sequences. RNA folding programs applied to the TER sequences show the presence of secondary structures necessary for telomerase activity, such as a yeast-like template boundary, pseudoknot, and a vertebrate-like three-way junction. These telomerase RNAs identified from filamentous fungi display conserved structural elements from both yeast and vertebrate TERs. These findings not only provide insights into the structure and evolution of a complex RNA but also provide molecular tools to further study telomere dynamics in filamentous fungi.
Pulmonary and systemic insults from inhalation injury can complicate the care of burn patients and contribute to significant morbidity and mortality. However, recent progress in diagnosis and treatment of inhalation injury has not kept pace with the care of cutaneous thermal injury. There are many challenges unique to inhalation injury that have slowed advancement, including deficiencies in our understanding of its pathophysiology, the relative difficulty and subjectivity of bronchoscopic diagnosis, the lack of diagnostic biomarkers, the necessarily urgent manner in which decisions are made about intubation, and the lack of universal recommendations for the application of mucolytics, anticoagulants, bronchodilators, modified ventilator strategies, and other measures. This review represents a summary of critical shortcomings in our understanding and management of inhalation injury identified by the American Burn Association’s working group on Cutaneous Thermal Injury and Inhalation Injury in 2018. It addresses our current understanding of the diagnosis, pathophysiology, and treatment of inhalation injury and highlights topics in need of additional research, including 1) airway repair mechanisms; 2) the airway microbiome in health and after injury; and 3) candidate biomarkers of inhalation injury.
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