The role of myristoylation in the membrane association of the Lassa virus matrix protein Z.

The Z protein is the matrix protein of arenaviruses and has been identified as the main driving force for budding. Both LCMV and Lassa virus Z proteins bud from cells in the absence of other viral proteins as enveloped virus-like particles. Z accumulates near the inner surface of the plasma membrane where budding takes place.

Nonpharmacologic therapy for hypertension: does it really work?

Nondrug therapy of hypertension really does work but requires strong motivation by both patient and physician. In addition to global health benefits, prescription of weight loss, exercise, moderation of salt and alcohol intake, Dietary Approach to Stop Hypertension (DASH) eating plan, and tobacco avoidance can decrease the risk for normotensive and prehypertensive patients of developing fixed hypertension. Initiating and maintaining a healthy lifestyle may be sufficient to avoid pharmacologic therapy for some patients and is a valuable adjunct to drug therapy for most.

New directions in the management of severe lupus nephritis.

Systemic lupus erythematosus, which predominantly affects young women, frequently is complicated by renal involvement. The presence of acute glomerulonephritis significantly adds to morbidity and mortality. Based on currently published clinical trials, induction therapy with cyclophosphamide combined with pulse corticosteroids is an efficacious treatment option to preserve renal function, and long-term data are available to support this choice.

The role of single N-glycans in proteolytic processing and cell surface transport of the Lassa virus glycoprotein GP-C.

Lassa virus glycoprotein is synthesised as a precursor (preGP-C) into the lumen of the endoplasmic reticulum. After cotranslational cleavage of the signal peptide, the immature GP-C is posttranslationally processed into the N-terminal subunit GP-1 and the C-terminal subunit GP-2 by the host cell subtilase SKI-1/S1P. The glycoprotein precursor contains eleven potential N-glycosylation sites.

[NiFe]-hydrogenases of Ralstonia eutropha H16: modular enzymes for oxygen-tolerant biological hydrogen oxidation.

Recent research on hydrogenases has been notably motivated by a desire to utilize these remarkable hydrogen oxidation catalysts in biotechnological applications. Progress in the development of such applications is substantially hindered by the oxygen sensitivity of the majority of hydrogenases. This problem tends to inspire the study of organisms such as Ralstonia eutropha H16 that produce oxygen-tolerant [NiFe]-hydrogenases.

Outcomes in African Americans and Hispanics with lupus nephritis.

Poor outcomes have been reported in African Americans and Hispanics compared to Caucasians with lupus nephritis. The purpose of this retrospective analysis was to identify independent predictors of outcomes in African Americans and Hispanics with lupus nephritis. In total, 93 African Americans, 100 Hispanics, and 20 Caucasians with a mean age of 28 +/- 13 years and an annual household income of 32.

Percutaneous management of perianastomotic stenosis in arteriovenous fistulae: results of a prospective study.

Surgical creation of new anastomosis has been proposed as the preferred treatment for perianastomotic stenoses of fistulae. However, disadvantages of surgical approach have included (1) frequent conversion of fistula to a graft by using synthetic graft material to create a new anastomosis, (2) shortening the length of the cannulation segment by proximal autologous arteriovenous neoanastomosis, and (3) abandoning the fistula altogether in favor of a synthetic graft. We report the results of a prospective study using percutaneous balloon angioplasty (PTA) to treat fistulae with perianastomotic lesions.

Low insulin-like growth factor binding protein-2 expression is responsible for increased insulin receptor substrate-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis.

Mesangial cells (MC) isolated from glomerulosclerosis-prone ragged, olygosyndactilism, pintail (ROP) mice retain a stable phenotype after exposure to elevated glucose concentrations, whereas MC from glomerulosclerosis-resistant C57BL/6 (C) mice do not. In NOD and db/db mice, the stable phenotype induced by diabetes consists of autocrine activation of the IGF-I signaling pathway. We hypothesized that high ambient glucose activates the IGF-I pathway in ROP but not in C MC.

Light-driven hydrogen production by a hybrid complex of a [NiFe]-hydrogenase and the cyanobacterial photosystem I.

In order to generate renewable and clean fuels, increasing efforts are focused on the exploitation of photosynthetic microorganisms for the production of molecular hydrogen from water and light. In this study we engineered a 'hard-wired' protein complex consisting of a hydrogenase and photosystem I (hydrogenase-PSI complex) as a direct light-to-hydrogen conversion system. The key component was an artificial fusion protein composed of the membrane-bound [NiFe] hydrogenase from the beta-proteobacterium Ralstonia eutropha H16 and the peripheral PSI subunit PsaE of the cyanobacterium Thermosynechococcus elongatus.

Electrochemical definitions of O2 sensitivity and oxidative inactivation in hydrogenases.

A new strategy is described for comparing, quantitatively, the ability of hydrogenases to tolerate exposure to O2 and anoxic oxidizing conditions. Using protein film voltammetry, the inherent sensitivities to these challenges (thermodynamic potentials and rates of reactions) have been measured for enzymes from a range of mesophilic microorganisms. In the absence of O2, all the hydrogenases undergo reversible inactivation at various potentials above that of the H+/H2 redox couple, and H2 oxidation activities are thus limited to characteristic "potential windows".

Factors associated with poor outcomes in patients with lupus nephritis.

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months.

Defining the role of mycophenolate mofetil in the treatment of proliferative lupus nephritis.

Systemic lupus erythematosus, which predominantly affects young women, is frequently complicated by renal involvement. The presence of acute glomerulonephritis significantly adds to morbidity and mortality. Cyclophosphamide has become the mainstay of treatment in patients with proliferative forms of lupus nephritis.

Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease.

Background: Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic conditions.

Objective: To evaluate the potential roles of positron emission tomography with fluorodeoxyglucose F 18 (18FDG-PET) and memory scores in identifying subjects with aMCI and in predicting progression to dementia.

Design, Setting, And Patients: Sixty-seven patients at European centers for neurologic and AD care who were diagnosed as having aMCI each underwent an extensive clinical and neuropsychological examination and an 18FDG-PET study.

Electrocatalytic hydrogen oxidation by an enzyme at high carbon monoxide or oxygen levels.

Use of hydrogen in fuel cells requires catalysts that are tolerant to oxygen and are able to function in the presence of poisons such as carbon monoxide. Hydrogen-cycling catalysts are widespread in the bacterial world in the form of hydrogenases, enzymes with unusual active sites composed of iron, or nickel and iron, that are buried within the protein. We have established that the membrane-bound hydrogenase from the beta-proteobacterium Ralstonia eutropha H16, when adsorbed at a graphite electrode, exhibits rapid electrocatalytic oxidation of hydrogen that is completely unaffected by carbon monoxide [at 0.

Barriers to successful care for chronic kidney disease.

Background: The National Kidney Foundation has formulated clinical practice guidelines for patients with chronic kidney disease (K/DOQI). However, little is know about how many patients actually achieve these goals in a dedicated clinic for chronic kidney disease.

Methods: We performed a cross-sectional analysis of 198 patients with an estimated glomerular filtration rate of less than 30 ml/min/1.

Creation of secondary arteriovenous fistulas: maximizing fistulas in prevalent hemodialysis patients.

National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) guideline 29 suggests that a patient should be evaluated for a secondary arteriovenous fistula (AVF) following each episode of dialysis access failure. Regretfully, it does not appear that this approach is used, even though recent data have emphasized that veins suitable for the creation of a secondary AVF can be identified in dialysis patients who are receiving dialysis via a synthetic arteriovenous graft (AVG) or other type of potentially dysfunctional vascular access. In this study nine patients (five with an AVG and four with an AVF) with vascular access dysfunction undergoing percutaneous interventions were evaluated for secondary AVF creation.

Requirements for heterologous production of a complex metalloenzyme: the membrane-bound [NiFe] hydrogenase.

By taking advantage of the tightly clustered genes for the membrane-bound [NiFe] hydrogenase of Ralstonia eutropha H16, broad-host-range recombinant plasmids were constructed carrying the entire membrane-bound hydrogenase (MBH) operon encompassing 21 genes. We demonstrate that the complex MBH biosynthetic apparatus is actively produced in hydrogenase-free hosts yielding fully assembled and functional MBH protein.

A model system for [NiFe] hydrogenase maturation studies: Purification of an active site-containing hydrogenase large subunit without small subunit.

The large subunit HoxC of the H2-sensing [NiFe] hydrogenase from Ralstonia eutropha was purified without its small subunit. Two forms of HoxC were identified. Both forms contained iron but only substoichiometric amounts of nickel.

Venous mapping using venography and the risk of radiocontrast-induced nephropathy.

Venous mapping using venography has been considered to be the gold standard for identifying veins suitable for arteriovenous fistula (AVF) creation. By utilizing a radiocontrast medium, however, venography introduces the risk of radiocontrast-induced nephropathy. The risk of this complication in the chronic kidney disease (CKD) population has not been previously studied.

Oligonucleotide-based microarray: a new improvement in microarray detection of plant viruses.

Microarrays are one of the new emerging methods in plant virology currently being developed by various laboratories. In this study, a new approach is described on the detection of plant viruses using short synthetic single-stranded oligomers (40 nt) instead of PCR products as capture probes. A microchip detecting potato viruses, PVA, PVS, PVM, PVX, PVY and PLRV, in both single and mixed infections was developed and tested.

Oxygen tolerance of the H2-sensing [NiFe] hydrogenase from Ralstonia eutropha H16 is based on limited access of oxygen to the active site.

Hydrogenases, abundant proteins in the microbial world, catalyze cleavage of H2 into protons and electrons or the evolution of H2 by proton reduction. Hydrogen metabolism predominantly occurs in anoxic environments mediated by hydrogenases, which are sensitive to inhibition by oxygen. Those microorganisms, which thrive in oxic habitats, contain hydrogenases that operate in the presence of oxygen.

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment.

Objective: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI).

Methods: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases.

Reduction of unusual iron-sulfur clusters in the H2-sensing regulatory Ni-Fe hydrogenase from Ralstonia eutropha H16.

The regulatory Ni-Fe hydrogenase (RH) from Ralstonia eutropha functions as a hydrogen sensor. The RH consists of the large subunit HoxC housing the Ni-Fe active site and the small subunit HoxB containing Fe-S clusters. The heterolytic cleavage of H(2) at the Ni-Fe active site leads to the EPR-detectable Ni-C state of the protein.

Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression.

Background: Alzheimer's disease (AD) is clinically characterized by cognitive impairment and behavioral disturbances. The aim of the study was to identify regional alterations in brain function associated with neuropsychiatric symptoms in early AD.

Methods: Patients underwent measures of cerebral glucose metabolism applying positron emission tomography (PET) and (18)F-fluorodeoxyglucose.