Flavobacterium johnsoniae SprA is a cell surface protein involved in gliding motility

Flavobacterium johnsoniae cells glide rapidly over surfaces by an unknown mechanism. Transposon-induced sprA mutants formed nonspreading colonies on agar, and the cells examined in wet mounts were deficient in attachment to surfaces and were almost completely nonmotile. Exposure of intact cells to proteinase K cleaved the 270-kDa SprA into several large peptides, suggesting that it is partially exposed on the cell surface.     

Predictors of mortality amongst recipients of implantable cardioverter defibrillators for secondary prevention of cardiac arrest

Background

Implantable Cardioverter-defibrillators (ICD) reduce mortality in survivors of cardiac arrest (CA). We investigated the predictors of mortality after ICD implantation in survivors of CA.

Methods

Retrospective review of clinical records and social security death index of all patients who received an ICD in a preexisting database of survivors of CA at the University of Pittsburgh Medical Center was performed. Multivariate analyses using the Cox proportional hazard model were performed with backward elimination to identify independent predictors of the time to death, and Kaplan-Meier curves were plotted.

Results

Eighty patients (64 men) with a mean age of 64.4±12.5 years were followed for 4.7±2.3 years after ICD implantation. Survival rates were 93.8%, 65% and 50% at 1, 5, and 10 years, respectively. Independent predictors of time to death were determined to include age (hazard ratio (HR) = 1.91 per 10-year increase, p = 0.003), serum creatinine ≥ 1.3 mg/dL (HR = 2.56, p = 0.004), and QRS width >120 ms (HR = 5.14, p = 0.012).

Conclusions

In this sample of ICD recipients secondary to CA, older age, elevated serum creatinine, and wider QRS duration were independent predictors of mortality. The presence of more than one risk factor in the same patient was associated with higher mortality rates. Whether interventions such as biventricular pacing can offset this increase risk of death warrants further investigation.     

Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: role of hydronephrosis

Recent studies in our laboratory using the Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rat models resulted in unexpectedly high mortality rates in all genotypes including healthy homozygous lean Zucker rats, possibly because of renal dysfunction. Therefore, we evaluated left ventricular (LV) and kidney morphology and function in young ZO, Zucker diabetic fatty obese (ZDFO), homozygous Zucker/ZDF lean (ZL), and Sprague-Dawley (SD) rats. Hydronephrosis was evident in ZL, ZO, and ZDFO but not SD kidneys. ZDFO rats exhibited impaired LV shortening and relaxation with increased arterial stiffness. LV wall thickness was lower and LV end-systolic wall stress was higher in ZDFO compared with SD rats. Plasma ANG II was lower in ZO and ZDFO rats, which may be a result of reduced renal parenchyma with hydronephrosis; norepinephrine was higher in ZDFO rats than SD controls. Covariate analysis indicated that LV end-systolic wall stress was associated with renal dysfunction. The presence of hydronephrosis and its association with LV dysfunction potentially limits the ZDF model for study of the effects of diabetes on renal and cardiovascular function.     

Closing in on the resting state of the Shaker K(+) channel

Membrane depolarization causes voltage-gated ion channels to transition from a resting/closed conformation to an activated/open conformation. We used voltage-clamp fluorometry to measure protein motion at specific regions of the Shaker Kv channel. This enabled us to construct new structural models of the resting/closed and activated/open states based on the Kv1.2 crystal structure using the Rosetta-Membrane method and molecular dynamics simulations. Our models account for the measured gating charge displacement and suggest a molecular mechanism of activation in which the primary voltage sensors, S4s, rotate by approximately 180 degrees as they move "outward" by 6-8 A. A subsequent tilting motion of the S4s and the pore domain helices, S5s, of all four subunits induces a concerted movement of the channel's S4-S5 linkers and S6 helices, allowing ion conduction. Our models are compatible with a wide body of data and resolve apparent contradictions that previously led to several distinct models of voltage sensing.     

Serum glucose-regulated protein 78 (GRP78) levels in COVID-19-associated mucormycosis: results of a case–control study

Mycopathologia - In experimental models, the expression of glucose-regulated protein 78 (GRP78) in endothelial cells played a role in the pathogenesis of mucormycosis. However, the role of GRP78 in...     

Vibrio cholerae MARTX toxin heterologous translocation of beta‐lactamase and roles of individual effector domains on cytoskeleton dynamics

The Vibrio cholerae MARTX_Vc toxin delivers three effector domains to eukaryotic cells. To study toxin delivery and function of individual domains, the rtxA gene was modified to encode toxin with an in‐frame beta‐lactamase (Bla) fusion. The hybrid RtxA::Bla toxin was Type I secreted from bacteria; and then Bla was translocated into eukaryotic cells and delivered by autoprocessing, demonstrating that the MARTX_Vc toxin is capable of heterologous protein transfer. Strains that produce hybrid RtxA::Bla toxins that carry one effector domain in addition to Bla were found to more efficiently translocate Bla. In cell biological assays, the actin cross‐linking domain (ACD) and Rho‐inactivation domain (RID) are found to cross‐link actin and inactivate RhoA, respectively, when other effector domains are absent, with toxin autoprocessing required for high efficiency. The previously unstudied alpha‐beta hydrolase domain (ABH) is shown here to activate CDC42, although the effect is ameliorated when RID is also present. Despite all effector domains acting on cytoskeleton assembly, the ACD was sufficient to rapidly inhibit macrophage phagocytosis. Both the ACD and RID independently disrupted polarized epithelial tight junction integrity. The sufficiency of ACD but strong selection for retention of RID and ABH suggests these two domains may primarily function by modulating cell signaling.