Connections between SNAREs and autophagy.

Autophagy involves the sequestration of portions of cytoplasm by double-membraned autophagosomes, which are then trafficked to lysosomes. After autophagosome-lysosome fusion, the contents of the autophagosomes are degraded by lysosomal hydrolases. SNAREs [soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein receptors] are molecules that mediate vesicular fusion events.

Obstetric healthcare providers' perceptions of communicating gestational weight gain recommendations to overweight/obese pregnant women.

Background: Gestational weight gain (GWG) is a major risk factor of poor pregnancy outcomes. Obese pregnant women frequently report bias and discrimination when dealing with healthcare providers (HCPs). Effective communication of GWG recommendations may impact risks.

Preemptive therapy versus valgancyclovir prophylaxis in cytomegalovirus-positive kidney transplant recipients receiving antithymocyte globulin induction.

International consensus guidelines on the management of cytomegalovirus (CMV) infections in kidney transplantation recommend the use of universal prophylaxis over preemptive therapy for the highest risk kidney transplant recipients (KTR), namely donor+/recipient - CMV serostatus. However, no universal recommendations have been made for R+ KTR undergoing antithymocyte globulin (ATG) induction. In this retrospective study, we compared 1-year outcomes among 24 R+ KTR who received 3 months of valgancyclovir prophylaxis with 72 R+ KTR who were subjected to a preemptive strategy.

Endothelial function is impaired across the stages of the menopause transition in healthy women.

Context: The stages of the menopause transition are characterized by changes in ovarian hormones and increased cardiovascular disease (CVD) risk factors and vasomotor symptoms that may adversely affect vascular health.

Objective: We tested the hypothesis that endothelial function, a predictor of CVD, would be reduced across the stages of the menopause transition, independent of CVD risk factors and vasomotor symptoms.

Design, Setting, And Participants: This was a cross-sectional study of 132 healthy women from the general community aged 22-70 yr, categorized as premenopausal (n = 33, 32 ± 6 yr; mean ± SD), early perimenopausal (n = 20, 49 ± 3 yr) or late perimenopausal (n = 22, 50 ± 4 yr), or early (n = 30, 55 ± 3 yr) or late postmenopausal (n = 27, 61 ± 4 yr).

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

Hysterectomy is associated with large artery stiffening in estrogen-deficient postmenopausal women.

Objective: Hysterectomy, with or without oophorectomy, is associated with increased cardiovascular disease (CVD) risk due, in part, to an adverse CVD risk factor profile. Large artery stiffening, a biomarker of vascular aging, increases the risk for CVD. We determined whether hysterectomy with or without bilateral oophorectomy (BLO) is associated with arterial stiffening in healthy postmenopausal women.

Cataract-causing defect of a mutant γ-crystallin proceeds through an aggregation pathway which bypasses recognition by the α-crystallin chaperone.

Background: The transparency of the eye lens depends upon maintenance of the native state of the γ- and β-crystallins, which is aided by the abundant chaperones αA- and αB-crystallin. Mature onset cataract, the leading cause of blindness worldwide, involves the polymerization of covalently damaged or partially unfolded crystallins into light-scattering aggregates. A number of single amino acid substitutions and truncations of γ-crystallins result in congenital cataract in both humans and mice, though in many cases the coupling between the protein alterations and the accumulation of aggregates is poorly defined.

The plasma membrane as a control center for autophagy.

Autophagosomes may derive membrane from diverse sources, including the plasma membrane, Golgi, endoplasmic reticulum and mitochondria. The plasma membrane contributes membrane to ATG12-ATG5-ATG16L1-positive phagophore precursor vesicles (LC3-negative) by both clathrin-dependent and -independent routes. We recently observed that ARF6 regulates autophagy and that this could be explained, at least in part, by its role in the generation of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2], which influences endocytic uptake of plasma membrane into autophagosome precursors.

Protein misfolding and aggregation in cataract disease and prospects for prevention.

The transparency of the eye lens depends on maintaining the native tertiary structures and solubility of the lens crystallin proteins over a lifetime. Cataract, the leading cause of blindness worldwide, is caused by protein aggregation within the protected lens environment. With age, covalent protein damage accumulates through pathways thought to include UV radiation, oxidation, deamidation, and truncations.

Measurement of autophagic activity in mammalian cells.

Macroautophagy (referred to herein as autophagy) is a process in which cells engulf portions of cytoplasm in double-membrane vesicles called autophagosomes. These autophagosomes can also capture protein oligomers associated with neurodegenerative diseases, infectious agents (like bacteria), and even organelles (like mitochondria). Autophagosomes are transported along microtubules towards the microtubule organizing center of cells, where the lysosomes are clustered.

Arf6 promotes autophagosome formation via effects on phosphatidylinositol 4,5-bisphosphate and phospholipase D.

Macroautophagy (in this paper referred to as autophagy) and the ubiquitin-proteasome system are the two major catabolic systems in cells. Autophagy involves sequestration of cytosolic contents in double membrane-bounded vesicles called autophagosomes. The membrane source for autophagosomes has received much attention, and diverse sources, such as the plasma membrane, Golgi, endoplasmic reticulum, and mitochondria, have been implicated.

Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women.

The mechanisms mediating arterial stiffening with aging and menopause are not completely understood. We determined whether administration of tetrahydrobiopterin (BH(4)), a critical cofactor for endothelial nitric oxide synthase to produce nitric oxide, would increase vascular endothelial-dependent vasodilatory tone and decrease arterial stiffness in estrogen-deficient postmenopausal women. Additionally, we examined whether the beneficial effects of estrogen on vascular function were possibly related to BH(4).

CCR5 expression is elevated on endocervical CD4+ T cells in healthy postmenopausal women.

Background: New HIV-1 infections are increasing in older American women largely through heterosexual transmission. Activated CD4+ T cells and CCR5 expression are linked to HIV-1 susceptibility, but whether these parameters are altered in the cervix of older women is unknown.

Methods: Whole blood and in some instances endocervical brush samples were collected from healthy premenopausal (n = 22) and postmenopausal women (n = 24).

Quantification of HIV-based lentiviral vectors: influence of several cell type parameters on vector infectivity.

A human immunodeficiency virus type (HIV-1)-based lentiviral vector pseudotyped with the vesicular stomatitis virus envelope glycoprotein and encoding the GFP reporter gene was used to evaluate different methods of lentiviral vector titration. GFP expression, viral DNA quantification and the efficiency of vector DNA integration were assayed after infection of conventional HIV-1-permissive cell lines and human primary adult fibroblasts with the vector. We found that vector titers based on GFP expression determined by flow cytometry may vary by more than 50-fold depending on the cell type and the promoter-cell combination used.

Functional analyses of mutants of the central core domain of an Avian Sarcoma/Leukemia Virus integrase.

Integrase (IN) is the enzyme responsible for the integration of the retroviral genome into the host cell DNA. Herein, three mutants of conserved residues (V79, S85 and I146) of the central core domain (CCD) of an Avian Sarcoma/Leukemia Virus IN were analyzed in vitro. Our data revealed (i) the inability of S85T mutant to form dimers and tetramers in the absence of DNA and (ii) a slightly reduced ability of V79A IN in tetramers formation.

High incidence of anticytomegalovirus drug resistance among D+R- kidney transplant recipients receiving preemptive therapy.

Anti-cytomegalovirus (CMV) prophylaxis is recommended in D+R- kidney transplant recipients (KTR), but is associated with a theoretical increased risk of developing anti-CMV drug resistance. This hypothesis was retested in this study by comparing 32 D+R- KTR who received 3 months prophylaxis (valganciclovir) with 80 D+R- KTR who received preemptive treatment. The incidence of CMV infections was higher in the preemptive group than in the prophylactic group (60% vs.

A crystal structure of the catalytic core domain of an avian sarcoma and leukemia virus integrase suggests an alternate dimeric assembly.

Integrase (IN) is an important therapeutic target in the search for anti-Human Immunodeficiency Virus (HIV) inhibitors. This enzyme is composed of three domains and is hard to crystallize in its full form. First structural results on IN were obtained on the catalytic core domain (CCD) of the avian Rous and Sarcoma Virus strain Schmidt-Ruppin A (RSV-A) and on the CCD of HIV-1 IN.

Autophagosome precursor maturation requires homotypic fusion.

Autophagy is a catabolic process in which lysosomes degrade intracytoplasmic contents transported in double-membraned autophagosomes. Autophagosomes are formed by the elongation and fusion of phagophores, which can be derived from preautophagosomal structures coming from the plasma membrane and other sites like the endoplasmic reticulum and mitochondria. The mechanisms by which preautophagosomal structures elongate their membranes and mature toward fully formed autophagosomes still remain unknown.

Physician privacy concerns when disclosing patient data for public health purposes during a pandemic influenza outbreak.

Background: Privacy concerns by providers have been a barrier to disclosing patient information for public health purposes. This is the case even for mandated notifiable disease reporting. In the context of a pandemic it has been argued that the public good should supersede an individual's right to privacy.

Suppression substractive hybridisation (SSH) and real time PCR reveal differential gene expression in the Pacific cupped oyster, Crassostrea gigas, challenged with Ostreid herpesvirus 1.

Virus-induced genes were identified using suppression subtractive hybridisation (SSH) from Pacific cupped oyster, Crassostrea gigas, haemocytes challenged by OsHV-1. A total of 304 clones from SSH forward library were sequenced. Among these sequences, some homologues corresponded to (i) immune related genes (macrophage express protein, IK cytokine, interferon-induced protein 44 or multicopper oxidase), (ii) apoptosis related genes (Bcl-2) and (iii) cell signalling and virus receptor genes (glypican).

How strong are passwords used to protect personal health information in clinical trials?

Background: Findings and statements about how securely personal health information is managed in clinical research are mixed.

Objective: The objective of our study was to evaluate the security of practices used to transfer and share sensitive files in clinical trials.

Methods: Two studies were performed.