Short transmembrane domains with high-volume exoplasmic halves determine retention of Type II membrane proteins in the Golgi complex

It is still unclear why some proteins that travel along the secretory pathway are retained in the Golgi complex whereas others make their way to the plasma membrane. Recent bioinformatic analyses on a large number of single-spanning membrane proteins support the hypothesis that specific features of the transmembrane domain (TMD) are relevant to the sorting of these proteins to particular organelles. Here we experimentally test this hypothesis for Golgi and plasma membrane proteins. Using the Golgi SNARE protein Sft1 and the plasma membrane SNARE protein Sso1 from Saccharomyces cerevisiae as model proteins, we modified the length of their TMDs and the volume of their exoplasmic hemi-TMD, and determined their subcellular localization both in yeast and mammalian cells. We found that short TMDs with high-volume exoplasmic hemi-TMDs confer Golgi membrane residence, whereas TMDs with low-volume exoplasmic hemi-TMDs, either short or long, confer plasma membrane residence to these proteins. Results indicate that the shape of the exoplasmic hemi-TMD, in addition to the length of the entire TMD, determine retention in the Golgi or exit to the plasma membrane of Type II membrane proteins.Fil: Quiroga, Rodrigo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); ArgentinaFil: Trenchi, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; ArgentinaFil: Gonzalez Montoro, Ayelén. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); ArgentinaFil: Valdez, Javier Esteban. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); ArgentinaFil: Maccioni, Hugo Jose Fernando. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); Argentin

Mammography Services Quality Assurance: Baseline Standards for Latin America and the Caribbean

Fil: Barr, Helen. No especifíca;Fil: Blanco, Susana Alicia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Salud. Instituto Nacional del Cáncer; ArgentinaFil: Butler, Priscilla. No especifíca;Fil: da Paz, María Angela. No especifíca;Fil: Fleitas, Ileana. No especifíca;Fil: Craig, George. No especifíca;Fil: Jimenez, Pablo. No especifíca;Fil: Luciani, Silvana. No especifíca;Fil: Manrique, Javier. No especifíca;Fil: Mazal, Jonathan. No especifíca;Fil: Medlen, Kayiba. No especifíca;Fil: MIller, Colie. No especifíca;Fil: Mora, Patricia. No especifíca;Fil: Valdez Moreno, Martha Elena. No especifíca;Fil: Mosodeen, Murrie. No especifíca;Fil: Mysler, Gustavo. No especifíca;Fil: Nuche-Berenguer, Bernardo. No especifíca;Fil: Pastel, Mary. No especifíca;Fil: Pinochet, Miguel. No especifíca;Fil: Sisney, Gale. No especifíca;Fil: Ruiz Trejo, Cesar. No especifíca;Fil: Saraiya, Mona. No especifíca;Fil: Solis, Esteban. No especifíca;Fil: Swann, Phillip. No especifíca

Garantía de calidad de los servicios de mamografía: Normas básicas para América Latina y el Caribe

Fil: Barr, Helen. No especifíca;Fil: Blanco, Susana Alicia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Salud. Instituto Nacional del Cáncer; ArgentinaFil: Albarracín, Virginia Helena. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Priscilla, Butler. No especifíca;Fil: da Paz, María Angela. No especifíca;Fil: Fleitas, Ileana. No especifíca;Fil: Jiménez, Pablo. No especifíca;Fil: Luciani, Silvana. No especifíca;Fil: Manrique, Javier. No especifíca;Fil: Mazal, Jonathan. No especifíca;Fil: Medlen, Kayiba. No especifíca;Fil: Miller, Collie. No especifíca;Fil: Mora, Patricia. No especifíca;Fil: Valdez Moreno, Martha Elena. No especifíca;Fil: Mosodeen, Murrie. No especifíca;Fil: Mysler, Gustavo. No especifíca;Fil: Nusche Berenguer, Bernardo. No especifíca;Fil: Pastel, Mary. No especifíca;Fil: Pinochet, Miguel. No especifíca;Fil: Ruiz Trejo, Cesar. No especifíca;Fil: Sisney, Gale. No especifíca;Fil: Saraiya, Mona. No especifíca;Fil: Solis, Esteban. No especifíca;Fil: Swann, Phillip. No especifíca

Argentine Intersociety Consensus on Urinary Infection 2018-2019

La Sociedad Argentina de Infectología y otras sociedades científicas han actualizado estas recomendaciones utilizando, además de información internacional, la de un estudio multicéntrico prospectivo sobre infecciones del tracto urinario del adulto realizado en Argentina durante 2016-2017. La bacteriuria asintomática debe ser tratada solo en embarazadas, a quienes también se las debe investigar sistemáticamente; los antibióticos de elección son nitrofurantoína, amoxicilina, amoxicilina-clavulánico, cefalexina y trimetoprimasulfametoxazol. Ante procedimientos que impliquen lesión con sangrado del tracto urinario se recomienda solicitar urocultivo para pesquisar bacteriuria asintomática, y, si resultara positivo, administrar antimicrobianos según sensibilidad desde inmediatamente antes hasta 24 horas luego de la intervención. En mujeres, la cistitis puede ser tratada con nitrofurantoina, cefalexina, o fosfomicina y no se recomienda usar trimetoprima-sulfametoxazol o fluoroquinolonas; en pielonefritis puede emplearse ciprofloxacina, cefixima o cefalexina si el tratamiento es ambulatorio o ceftriaxona, cefazolina o amikacina si es hospitalario. En los hombres, las infecciones del tracto urinario se consideran siempre complicadas. Se recomienda tratamiento con nitrofurantoina o cefalexina por 7 días, o bien monodosis con fosfomicina. Para la pielonefritis en hombres se sugiere ciprofloxacina, ceftriaxona o cefixima si el tratamiento es ambulatorio y ceftriaxona o amikacina si es hospitalario. Se sugiere tratar las prostatitis bacterianas agudas con ceftriaxona o gentamicina. En cuanto a las prostatitis bacterianas crónicas, si bien su tratamiento de elección hasta hace poco fueron las fluoroquinolonas, la creciente resistencia y ciertasdudas sobre la seguridad de estas drogas obligan a considerar el uso de alternativas como fosfomicina.The Argentine Society of Infectious Diseases and other scientific societies have updated these recommendations based on data on urinary tract infections in adults obtained from a prospective multicenter study conducted in Argentina during 2016-2017. Asymptomatic bacteriuria should be treated only in pregnant women, who should also be systematically investigated; the antibiotics of choice are nitrofurantoin, amoxicillin, clavulanic/amoxicillin, cephalexin and trimethoprim-sulfamethoxazole. In procedures involving injury to the urinary tract with bleeding, it is recommended to request urine culture and, in the presence of bacteriuria, antimicrobial treatment according to sensitivity should be prescribed from immediately before up to 24 hours after the intervention. In women, cystitis can be treated with nitrofurantoin, cephalexin or fosfomycin, while trimethoprim-sulfamethoxazole and fluoroquinolones are not recommended; pyelonephritis can be treated with ciprofloxacin, cefixime or cephalexin in ambulatory women or ceftriaxone, cefazolin or amikacin in those who are hospitalized. In men, urinary tract infections are always considered complicated; nitrofurantoin or cephalexin are recommended for 7 days, alternatively fosfomycin should be given in a single dose. In men, ciprofloxacin, ceftriaxone or cefixime are suggested for pyelonephritis on ambulatory treatment whereas ceftriaxone or amikacin are recommended for hospitalized patients. Acute bacterial prostatitis can be treated with ceftriaxone or gentamicin. Fluoroquinolones were the choice treatment for chronic bacterial prostatitis until recently; they are no longer recommended due to the increasing resistance and recent concerns regarding the safety of these drugs; alternative antibiotics such as fosfomycin are to be considered.Fil: Nemirovsky, Corina. Sociedad Argentina de Infectologia; ArgentinaFil: Lopez Furst, María José. Sociedad Argentina de Infectologia; ArgentinaFil: Pryluka, Daniel. Sociedad Argentina de Infectologia; ArgentinaFil: de Vedia, Lautaro. Sociedad Argentina de Infectologia; ArgentinaFil: Scapellato, Pablo. Sociedad Argentina de Infectologia; ArgentinaFil: Colque, Angel. Sociedad Argentina de Infectologia; ArgentinaFil: Barcelona, Laura. Sociedad Argentina de Infectologia; ArgentinaFil: Desse, Javier. Sociedad Argentina de Infectologia; ArgentinaFil: Caradont, Matías. Sociedad Argentina de Urología; ArgentinaFil: Varcasia, Daniel. Sociedad Argentina de Urología; ArgentinaFil: Ipohorski,Gabriel. Federación Argentina de Urología; ArgentinaFil: Votta, Roberto. Federación Argentina de Sociedades de Ginecología y Obstetricia; ArgentinaFil: Zylberman, Marcelo. Sociedad Argentina de Medicina; ArgentinaFil: Romani, Adriana de Fátima. Sociedad Argentina de Medicina; ArgentinaFil: Valdez, Pascual. Sociedad Argentina de Medicina; ArgentinaFil: Penini, Magdalena. Sociedad Argentina de Bacteriología, Micología y Parasitología Clínica; ArgentinaFil: De Paulis, Adriana. Sociedad Argentina de Bacteriología, Micología y Parasitología Clínica; ArgentinaFil: Lucero, Celeste. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Sandor, Andres. Sociedad Argentina de Infectología; ArgentinaFil: Contreras, Rosita. Sociedad Argentina de Infectología; ArgentinaFil: Nannini, Esteban. Sociedad Argentina de Infectología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Gañete, Marcelo. Sociedad Argentina de Infectología; ArgentinaFil: Ralli, Hector. Sociedad Argentina de Infectología; ArgentinaFil: Lopardo, Gustavo. Sociedad Argentina de Infectología; ArgentinaFil: Mykietiuk, Analia. Sociedad Argentina de Infectología; ArgentinaFil: Aronson, Sandra. Sociedad Argentina de Infectología; ArgentinaFil: Fernández Laus, Adriana. Sociedad Argentina de Infectología; ArgentinaFil: Fernández Garces, Alejandro. Sociedad Argentina de Infectología; ArgentinaFil: Rodríguez, Claudia. Sociedad Argentina de Infectología; ArgentinaFil: Chattas, Ana. Sociedad Argentina de Infectología; ArgentinaFil: Farina, Javier. Sociedad Argentina de Infectología; ArgentinaFil: Clara, Liliana. Sociedad Argentina de Infectología; ArgentinaFil: Nuccetelli, Yanina. Sociedad Argentina de Infectología; ArgentinaFil: Amalfa, Flavia. Sociedad Argentina de Infectología; Argentin

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of the Splitting Function in &ITpp &ITand Pb-Pb Collisions at root&ITsNN&IT=5.02 TeV

Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.Peer reviewe

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe