Structural basis for feed-forward transcriptional regulation of membrane lipid homeostasis in Staphylococcus aureus.

The biosynthesis of membrane lipids is an essential pathway for virtually all bacteria. Despite its potential importance for the development of novel antibiotics, little is known about the underlying signaling mechanisms that allow bacteria to control their membrane lipid composition within narrow limits. Recent studies disclosed an elaborate feed-forward system that senses the levels of malonyl-CoA and modulates the transcription of genes that mediate fatty acid and phospholipid synthesis in many Gram-positive bacteria including several human pathogens.

Risk factors associated with the colonization of Ontario layer chicken flocks with Brachyspira species.

Brachyspira species are frequent colonizers of the gastrointestinal tract in a variety of domestic animals, including birds. In chickens, Brachyspira species are associated with a clinical condition known as avian intestinal spirochetosis (AIS), a disease characterized by chronic diarrhoea, weight loss, low egg production, and faecal-stained eggs. The purpose of this study was to identify risk factors associated with the presence of Brachyspira species in Ontario layer chicken flocks.

Informed consent in refractive eye surgery: learning from patients and the courts.

Refractive eye laser surgery involves ablation of the cornea using excimer laser to correct short or long sightedness and thus negate the need for glasses and/or contact lenses. With the doctrine of informed consent often central to claims of medical negligence in this area, we examine the attitudes, understanding and recall of patients to consent for refractive surgery and outline the relevant law. 102 patients undergoing first time refractive surgery were analysed to examine their understanding and recall of the consenting process.

The postbinding activity of scavenger receptor class B type I mediates initiation of hepatitis C virus infection and viral dissemination.

Unlabelled: Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor highly expressed in the liver and modulating HDL metabolism. Hepatitis C virus (HCV) is able to directly interact with SR-BI and requires this receptor to efficiently enter into hepatocytes to establish productive infection. A complex interplay between lipoproteins, SR-BI and HCV envelope glycoproteins has been reported to take place during this process.

[Usefulness of topical cidofovir treatment for recalcitrant molluscum contagiosum in immunocompromised children].

Molluscum contagiosum (MC) is common and often numerous and recalcitrant in immunocompromised children. The response to available treatments is frequently unsatisfactory. Cidofovir is a nucleoside analog of the deoxycytidine antiviral drug approved for the intravenous treatment of cytomegalovirus retinitis in AIDS patients.

Altered expression of the poly(ADP-ribosyl)ation enzymes in uveal melanoma and regulation of PARG gene expression by the transcription factor ERM.

Purpose: Poly(ADP-ribosyl)ation is a reversible post-translational modification that requires the contribution of the enzymes poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG). Our study explores expression and activity of PARP-1 and PARG in uveal melanoma cell lines with varying tumorigenic properties.

Methods: Gene profiling on microarrays was conducted using RNA prepared from the uveal melanoma cell lines T97, T98, T108, and T115.

Elevated CETP activity improves plasma cholesterol efflux capacity from human macrophages in women.

Objective: We aim to identify the impact of endogenous cholesteryl ester transfer protein (CETP) activity on plasma capacity to mediate free cholesterol efflux from human macrophages.

Methods And Results: Endogenous plasma CETP activity was measured in a population of 348 women. We defined a low CETP group corresponding to subjects displaying an endogenous plasma CETP activity within the first tertile and a high CETP group corresponding to subjects with an endogenous plasma CETP activity within the third tertile.

'What matters to me': an international online survey of people treating, affected by and living with lung cancer.

Aim: Lung cancer is a common malignancy that occurs worldwide and generally has a poor prognosis. Its diagnosis presents significant physical and emotional challenges for patients and their family, friends and caregivers (FFCs). This study aimed to gain insights into patients' and FFCs' perspectives regarding lung cancer and its treatment, as well as physicians' perceptions of patients' thoughts about their illness.

Human ATP-binding cassette G1 controls macrophage lipoprotein lipase bioavailability and promotes foam cell formation.

Objective: The physiological function of the ATP-binding cassette G1 (ABCG1) transporter in humans is not yet elucidated, as no genetic disease caused by ABCG1 mutations has been documented. The goal of our study was, therefore, to investigate the potential role(s) of ABCG1 in lipid metabolism in humans.

Methods And Results: Here we report that among the 104 polymorphisms present in the ABCG1 gene, the analysis of the frequent functional rs1893590 and rs1378577 single nucleotide polymorphisms located in the regulatory region of ABCG1 in the Regression Growth Evaluation Statin Study population revealed that both ABCG1 single nucleotide polymorphisms were significantly associated with plasma lipoprotein lipase (LPL) activity.

Characterization of hepatitis C virus particle subpopulations reveals multiple usage of the scavenger receptor BI for entry steps.

Hepatitis C virus (HCV) particles assemble along the very low density lipoprotein pathway and are released from hepatocytes as entities varying in their degree of lipid and apolipoprotein (apo) association as well as buoyant densities. Little is known about the cell entry pathway of these different HCV particle subpopulations, which likely occurs by regulated spatiotemporal processes involving several cell surface molecules. One of these molecules is the scavenger receptor BI (SR-BI), a receptor for high density lipoprotein that can bind to the HCV glycoprotein E2.

Excimer laser photorefractive keratectomy for low to moderate myopia using a 5.0 mm treatment zone and no transitional zone: 16-year follow-up.

Purpose: To evaluate the safety and efficacy of photorefractive keratectomy (PRK) 16 years postoperatively.

Setting: Refractive Laser Suite, Mater Private Hospital, Dublin, Ireland.

Design: Cohort study.

Identification and characterization of new gain-of-function mutations in the PCSK9 gene responsible for autosomal dominant hypercholesterolemia.

Background: The identification of mutations in PCSK9 (proprotein convertase subtilisin kexin9) in autosomal dominant hypercholesterolemia (ADH), has revealed the existence of a new player in cholesterol homeostasis. PCSK9 has been shown to enhance the degradation of the LDL receptor (LDLR) at the cell surface. Gain-of-function mutations of PCSK9 induce ADH and are very rare, but their identification is crucial in studying PCSK9's role in hypercholesterolemia, its detailed trafficking pathway and its impact on the LDLR.

Mechanistic insights into the retaining glucosyl-3-phosphoglycerate synthase from mycobacteria.

Considerable progress has been made in recent years in our understanding of the structural basis of glycosyl transfer. Yet the nature and relevance of the conformational changes associated with substrate recognition and catalysis remain poorly understood. We have focused on the glucosyl-3-phosphoglycerate synthase (GpgS), a "retaining" enzyme, that initiates the biosynthetic pathway of methylglucose lipopolysaccharides in mycobacteria.

Reverse cholesterol transport in familial hypercholesterolemia.

Purpose Of Review: Familial hypercholesterolemia is characterized by a major elevation in circulating LDL-cholesterol levels, cholesterol deposition within the arterial wall and an increased risk of premature coronary artery disease. The reverse cholesterol transport (RCT) is now considered as a key process that protects against development of atherosclerosis. The major antiatherogenic action of HDL particles is intimately linked to their determinant role in RCT pathway.

Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia.

In familial hypercholesterolemia (FH), low HDL cholesterol (HDL-C) levels are associated with functional alterations of HDL particles that reduce their capacity to mediate the reverse cholesterol transport (RCT) pathway. The objective of this study was to evaluate the consequences of LDL apheresis on the efficacy of the RCT pathway in FH patients. LDL apheresis markedly reduced abnormal accelerated cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer from HDL to LDL, thus reducing their CE content.

Functionality of postprandial larger HDL2 particles is enhanced following CETP inhibition therapy.

Objective: To evaluate the impact of CETP inhibition on the capacity of individual postprandial HDL subspecies to promote key steps of the reverse cholesterol transport pathway.

Methods: The capacity of HDL particles to mediate cellular free cholesterol efflux and selective hepatic uptake of cholesteryl esters was evaluated throughout postprandial phase (0-8 h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10 mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10 mg/d) in 16 patients displaying low HDL-C levels (<40 mg/dl).

Results: The larger HDL2b and HDL2a subfraction displayed a superior capacity to mediate cellular free cholesterol efflux via both SR-BI and ABCG1-dependent pathways than smaller HDL3 subspecies.

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66.

We have previously demonstrated that measurement of tissue concentrations of the secretogranin II (SgII or SCG2 as listed in the HUGO database)-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas and that EM66 represents a sensitive plasma marker of pheochromocytomas. Here, we investigated the gene expression and protein production of SgII in 13 normal adrenal glands, and 35 benign and 16 malignant pheochromocytomas with the goal to examine the molecular mechanisms leading to the marked variations in the expression of EM66 in tumoral chromaffin tissue. EM66 peptide levels were 16-fold higher in benign than in malignant pheochromocytomas and had an area under the receiver-operating characteristic curve of 0.

Glycolytic and non-glycolytic functions of Mycobacterium tuberculosis fructose-1,6-bisphosphate aldolase, an essential enzyme produced by replicating and non-replicating bacilli.

The search for antituberculosis drugs active against persistent bacilli has led to our interest in metallodependent class II fructose-1,6-bisphosphate aldolase (FBA-tb), a key enzyme of gluconeogenesis absent from mammalian cells. Knock-out experiments at the fba-tb locus indicated that this gene is required for the growth of Mycobacterium tuberculosis on gluconeogenetic substrates and in glucose-containing medium. Surface labeling and enzymatic activity measurements revealed that this enzyme was exported to the cell surface of M.

Lupus attributable to anti-TNF therapy and revealed by interstitial granulomatous dermatitis.

Interstitial granulomatous dermatitis belongs to the group of aseptic cutaneous granulomas. It is a histopathological entity encountered in various pathological situations, such as polyarthritis including rheumatoid arthritis, but also systemic lupus erythematosus. It may also occur after systemic administration of medication, thus representing a drug-induced, interstitial granulomatous outbreak.

Interleukin-6 protects human macrophages from cellular cholesterol accumulation and attenuates the proinflammatory response.

Cholesterol-laden monocyte-derived macrophages are phagocytic cells characteristic of early and advanced atherosclerotic lesions. Interleukin-6 (IL-6) is a macrophage secretory product that is abundantly expressed in atherosclerotic plaques but whose precise role in atherogenesis is unclear. The capacity of macrophages to clear apoptotic cells, through the efferocytosis mechanism, as well as to reduce cellular cholesterol accumulation contributes to prevent plaque progression and instability.

On-farm study of human contact networks to document potential pathways for avian influenza transmission between commercial poultry farms in Ontario, Canada.

Human movements associated with poultry farming create contact networks that might facilitate transmission of avian influenza (AI) between farms during outbreaks. In Canada, no information is available about how these networks connect poultry farms. The purpose of this study was to document human contacts between commercial poultry farms in Ontario, Canada, to learn how AI might be transmitted during outbreaks.

Atheroprotective reverse cholesterol transport pathway is defective in familial hypercholesterolemia.

Objective: Low high-density lipoprotein (HDL) cholesterol levels are frequently observed in familial hypercholesterolemia (FH) and might be associated with functional alterations of HDL particles that may influence their efficaciousness in the reverse cholesterol transport pathway.

Methods And Results: We evaluated key steps of the reverse cholesterol transport, ie, cellular free cholesterol efflux, cholesteryl ester transfer protein-mediated cholesteryl ester (CE) transfer from HDL to apolipoprotein B-containing lipoproteins, and hepatic HDL-CE uptake, in patients displaying FH (n = 12) and in healthy normolipidemic control subjects (n = 12). Large HDL2 particles isolated from FH patients displayed a reduced capacity to mediate free cholesterol efflux via both scavenger receptor-BI- and ABCG1-dependent pathways.

Age-dependent rat retinal ganglion cell susceptibility to apoptotic stimuli: implications for glaucoma.

Background: This paper seeks to investigate differences between the neonatal and adult retinal ganglion cell populations to apoptotic death stimuli. DESIGN AND SAMPLES: In vitro and ex vivo paradigms involving P6 and P60 Sprague-Dawley rat retinal explants and retinal ganglion cells were employed.

Methods:  Postnatal day 6 (P6) and 60 (P60) Sprague-Dawley retinal ganglion cells and retinal explants were either serum starved or subjected to excitotoxicity using calcium ionophore A23187.