The ribosomal maturation factor P from Mycobacterium smegmatis facilitates the ribosomal biogenesis by binding to the small ribosomal protein S12.

The ribosomal maturation factor P (RimP) is a highly conserved protein in bacteria and has been shown to be important in ribosomal assembly in Escherichia coli Because of its central importance in bacterial metabolism, RimP represents a good potential target for drug design to combat human pathogens such as Mycobacterium tuberculosis However, to date, the only RimP structure available is the NMR structure of the ortholog in another bacterial pathogen, Streptococcus pneumoniae Here, we report a 2.2 Å resolution crystal structure of MSMEG_2624, the RimP ortholog in the close M. tuberculosis relative Mycobacterium smegmatis, and using in vitro binding assays, we show that MSMEG_2624 interacts with the small ribosomal protein S12, also known as RpsL. Further analyses revealed that the conserved residues in the linker region between the N- and C-terminal domains of MSMEG_2624 are essential for binding to RpsL. However, neither of the two domains alone was sufficient to form strong interactions with RpsL. More importantly, the linker region was essential for in vivo ribosomal biogenesis. Our study provides critical mechanistic insights into the role of RimP in ribosome biogenesis. We anticipate that the MSMEG_2624 crystal structure has the potential to be used for drug design to manage M. tuberculosis infections.

Hypermethylation of NF-κB-Activating Protein-Like (NKAPL) Promoter in Hepatocellular Carcinoma Suppresses Its Expression and Predicts a Poor Prognosis.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate partially due to frequent recurrence and no efficient therapy. Promoter hypermethylation of tumor suppressor genes has been demonstrated as one of the molecular mechanisms contributing to tumorigenesis and progression in HCC. This study aims to investigate regulation of NKAPL expression by promoter methylation and its clinical relevance as a biomarker for HCC. METHODS: We measured mRNA expression of NKAPL in 5 HCC cell lines and a cohort of 62 pairs of primary HCC tumor and their adjacent non-cancer liver tissues. NKAPL protein expression on HCC cell lines and clinical samples was assessed by Western blot and immunohistochemistry, respectively. Association analyses between NKAPL expression and clinicopathologic characteristics in the cohort were conducted. Methylation statuses of NKAPL promoter in 18 pairs of tumor and adjacent non-tumor HCC samples were studied using methylation-specific PCR. Biological functions of NKAPL in HCC were investigated by ectopic expression of NKAPL in HCC cells, and cell viability and cell cycle analyses were performed. RESULTS: Our present study showed suppressed expression and promoter hypermethylation are common events in HCC. Demethylation experiment in HCC cells demonstrated that the NKAPL expression was regulated by promoter methylation. In addition, high methylation level of NKAPL and its low expression predict poor outcome. Furthermore, ectopic expression of NKAPL in the HCC cells inhibited cell growth. CONCLUSIONS: Our findings suggest that methylation of NKAPL is a frequent event and is a potential prognosis biomarker in HCC.

Anterolateral papillary muscle rupture in Staphylococcus aureus endocarditis due to direct bacterial invasion of papillary muscle.

Rupture of papillary muscles due to infective endocarditis is a very rare event. We report a case of anterolateral papillary muscle rupture caused by Staphylococcus aureus endocarditis, due to direct bacterial invasion of the papillary muscle, resulting in severe mitral regurgitation.

Peri-operative Levosimendan in Patients Undergoing Cardiac Surgery: An Overview of the Evidence.

Levosimendan, a calcium sensitiser, has recently emerged as a valuable agent in the peri-operative management of cardiac surgery patients. Levosimendan is a calcium-sensitising ionodilator. By binding to cardiac troponin C and reducing its calcium-binding co-efficient, it enhances myofilament responsiveness to calcium and thus enhances myocardial contractility without increasing oxygen demand. Current evidence suggests that levosimendan enhances cardiac function after cardiopulmonary bypass in patients with both normal and reduced left ventricular function. In addition to being used as post-operative rescue therapy for low cardiac output syndrome, a pre-operative levosimendan infusion in high risk patients with poor cardiac function may reduce inotropic requirements, the need for mechanical support, the duration of intensive care admissions as well as post-operative mortality. Indeed, it is these higher-risk patients who may experience a greater degree of benefit. Larger, multicentre randomised trials in cardiac surgery will help to elucidate the full potential of this agent.

Metastatic small bowel neuroendocrine tumour and carcinoid heart disease with aortic valve involvement-a rare occurrence.

Carcinoid disease of the heart commonly affects the tricuspid and pulmonary valves causing thickening and stenosis. However in very rare circumstances, the disease can also involve the mitral and aortic valves. We present an unusual case of left sided carcinoid heart disease (CHD) and triple valve replacement without the presence of proven intra-cardiac shunts or bronchial carcinoid lesions.

Early results of the Sorin® Perceval S sutureless valve: systematic review and meta-analysis.

BACKGROUND: Minimally invasive aortic valve replacement (MAVR) has demonstrated a benefit with respect to increased patient satisfaction due to minimised pain and earlier recovery. Sutureless valves may benefit MAVR and conventional aortic valve replacement (AVR) by reducing operative times and blood transfusion requirements. The Perceval valve (Sorin, Salluggia, Italy) is a self-expanding prosthesis made from bovine pericardium mounted in a nitinol stent, designed to simplify the implantation of an aortic valve. This meta-analysis evaluates the clinical, haemodynamic, and survival outcomes of the Perceval sutureless valve. METHODS: An electronic search of 4 databases was performed from January 2000 to December 2016. Primary outcomes included mortality and stroke. Secondary outcomes included minimally invasive access, paravalvular leak, overall long-term survival, postoperative echocardiographic findings, and functional class improvement. RESULTS: After the application of inclusion and exclusion criteria, 14 of 66 relevant articles were selected for assessment. Of these 14 studies, a total number of 2,505 patients were included. The current evidence on the Perceval valve for aortic valve disease is limited to observational studies only. Minimally invasive surgery was performed in 976 patients, of which 336 were via the right anterior thoracotomy approach. The Perceval M and L sutureless valves were the most frequently used, 782 and 770 respectively. The incidence of major adverse events included 30-day mortality (0 to 4.9%), cerebrovascular accident (0 to 3%), permanent pacemaker insertion (0 to 17%), moderate to severe paravalvular leak (0 to 8.6%), and re-operation (0 to 4.8%). Post-operative mean aortic valve gradient ranged from 9 to 15.9 mmHg and post-operative New York Heart Association (NYHA) Class I or II ranged from 82% to 96%. The 1-year survival ranged from 86% to 100%; and 5-year survival was 71.3% to 85.5% in two studies. CONCLUSIONS: The Perceval valve is associated with excellent post-operative results in MAVR and in conventional AVR. Larger randomised controlled studies are required to evaluate the long-term efficacy of the prosthesis.