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Leptospirosis is the most common zoonotic disease caused by pathogenic Leptospira, which is classified into three groups according to virulence. Its pathogenic and intermediate species contain leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic strains. In this study, we presented the crystal structure of LSS_11580 (rLRR20) from pathogenic L. santarosai serovar Shermani. X-ray diffraction at a resolution of 1.99 Å revealed a horseshoe-shaped structure containing seven a-helices and five ß-sheets. Affinity assays indicated that rLRR20 interacts with E-cadherin on the cell surface. Interestingly, its binds to the extracellular (EC) 1 domain in human epithelial (E)-cadherin, which is responsible for binding to another E-cadherin molecule in neighboring cells. Several charged residues on the concave face of LRR20 were predicted to interact with EC1 domain. In the affinity assays, these charged residues were replaced by alanine, and their affinities to E-cadherin were measured. Three vital residues and mutation variants of LRR20, namely D56A, E59A, and E123A, demonstrated significantly reduced affinity to E-cadherin compared with the control. Besides, we also demonstrated that rLRR20 induced the expression of neutrophil gelatinase-associated lipocalin (NGAL) in HK2 cells. The low ability of the three mutation variants to induce NGAL expression further demonstrates this induction. The present findings indicate that LRR20 from pathogenic Leptospira binds to E-cadherin and interacts with its EC1 domain. In addition, its induction of NGAL expression in HK2 cells is associated with acute kidney injury in human. [ABSTRACT FROM AUTHOR]

Rationale: Patients with sepsis who survive to hospital discharge may present with ongoing high morbidity and mortality. However, little is known about the risk of long-term, all-cause mortality and cardiovascular outcomes after sepsis.Objectives: Our study aimed to investigate the long-term clinical outcomes in sepsis survivors.Methods: In this nationwide population-based study, data from patients with sepsis were retrieved from Taiwan's National Health Insurance Research Database between 2000 and 2002. Each sepsis survivor was 1:1 propensity-matched to control subjects from two different control populations: subjects who were in the general population and subjects who were hospitalized for a nonsepsis diagnosis. The primary outcomes were all-cause mortality, major adverse cardiovascular events, myocardial infarction, heart failure, stroke, and sudden cardiac death or ventricular arrhythmia.Measurements and Main Results: Compared with matched population control subjects, sepsis survivors had higher risks of all-cause mortality (hazard ratio [HR], 2.18; 95% confidence interval [CI], 2.14-2.22), major adverse cardiovascular events (HR, 1.37; 95% CI, 1.34-1.41), ischemic stroke (HR, 1.27; 95% CI, 1.23-1.32), hemorrhagic stroke (HR, 1.36; 95% CI, 1.26-1.46), myocardial infarction (HR, 1.22; 95% CI, 1.14-1.30), heart failure (HR, 1.48; 95% CI, 1.43-1.53), and sudden cardiac death or ventricular arrhythmia (HR, 1.65; 95% CI, 1.57-1.74). Similar results, although slightly attenuated risks, were found when comparisons were made with hospitalized control subjects without sepsis.Conclusions: These data indicate that sepsis survivors had substantially increased risks of subsequent all-cause mortality and major adverse cardiovascular events at 1 year after discharge, which persisted for up to 5 years after discharge. [ABSTRACT FROM AUTHOR]

Background: Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.Objective: To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM.Design: Nationwide study using Taiwan's National Health Insurance Research Database.Setting: Taiwan.Patients: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined.Measurements: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.Results: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.Limitation: Observational study design.Conclusion: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Spo0J (stage 0 sporulation protein J, a member of the ParB superfamily) is an essential component of the ParABS (partition system of ParA, ParB, and parS)-related bacterial chromosome segregation system. ParB (partition protein B) and its regulatory protein, ParA, act cooperatively through parS (partition S) DNA tofacilitate chromosome segregation. ParB binds to chromosomal DNA at specific parS sites as well as the neighboring nonspecific DNA sites. Various ParB molecules can associate together and spread along the chromosomal DNA. ParB oligomer and parS DNA interact together toform a high-order nucleoprotein that is required for the loading of the structural maintenance of chromosomes proteins onto the chromosome for chromosomal DNA condensation. In this report, we characterized the binding of parS and Spo0J from Helicobacter pylori (HpSpo0J) and solved the crystal structure of the C-terminal domain truncated protein (Ct-HpSpo0J)-parS complex. Ct-HpSpo0J folds into an elongated structure that includes a flexible N-terminal domain for protein-protein interaction and a conserved DNA-binding domain for parS binding. Two Ct-HpSpo0J molecules bind with one parS. Ct-HpSpo0J interacts vertically and horizontally with its neighbors through the N-terminal domain toform an oligomer. These adjacent and transverse interactions are accomplished via a highly conserved arginine patch: RRLR. These interactions might be needed for molecular assembly of a highorder nucleoprotein complex and for ParB spreading. A structural model for ParB spreading and chromosomal DNA condensation that lead to chromosome segregation is proposed. [ABSTRACT FROM AUTHOR]

The article presents information about an 89-year-old man who was admitted to a hospital due to an intermittent anterior chest pain. The chest radiography of the patient found a thin-walled cavity and a mass with an irregular border inside the cavity, which was located in the superior segment of the left lower lobe. It is informed that the patient went through various medical screening procedures and the final pathologic diagnosis showed adenocarcinoma of lungs in the patient.

Evaluates the strength of microcomponents fabricated using wet and dry etching techniques. Importance of finite element model on the prediction of strength of microridge structures; Validation on the use of macroscopic model on predicting the strength of micromachine components.