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PubMed1983

Geometry and orientation of neuronal processes in cat primary auditory cortex (AI) related to characteristic-frequency maps.

Microelectrode mapping and horseradish peroxidase oxidase histochemistry were combined to study the relationship between the characteristic-frequency representation and the intrinsic connectivity of the primary auditory cortex in the cat. Small extracellular iontophoretic injections of horseradish peroxidase within the characteristic-frequency map resulted in labeling of neuronal processes that, in the tangential plane, radiated out asymmetrically from the injection site over distances of several millimeters. The heaviest concentration of labeled fibers was along an axis parallel with the orientation of the isofrequency line within which the injection had been made. Thus, primary field neurons that have the same or a similar characteristic frequency have the potential of being preferentially interconnected.

Animals↗
PubMed1995

Transcriptional regulation of the cholesteryl ester transfer protein gene by the orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1.

We have defined a 105-base pair tissue-restricted promoter for the cholesteryl ester transfer protein (CETP) gene that contains a nuclear hormone receptor response element essential for transcriptional activity. DNaseI protection and electrophoretic mobility shift assays showed specific binding of nuclear extracts from HepG2 (hepatic) and Caco-2 (intestinal) cells (expressing cell types) to 3 sites (designated A (-26 to -57), B (-59 to -87), and C (-93 to -118)) within the 105-base pair minimal promoter element between -138 and -33. Mutagenesis studies indicated that the function of the promoter was dependent upon synergistic interactions between transcription factors bound to these sites. Mutation of site C reduced transcription by 50 and 80%, respectively, in HepG2 and Caco-2 cells, and electrophoretic mobility shift assays showed that nuclear hormone receptors, including ARP-1 and its homologue Ear-3/COUP-TF, were occupants of site C in both of these cell types. Overexpression of ARP-1 or Ear-3/COUP-TF with CETP promoter/chloramphenicol acetyltransferase gene reporter plasmids repressed transcriptional activity of the CETP promoter containing sequences up to -300, but activated transcription in the context of larger constructs containing sequences up to -636. Thus ARP-1 may assume a dichotomous role as both a transcriptional repressor and a transcriptional activator dependent on the promoter context. In addition, the architecture of the CETP gene promoter suggests that its expression is under the control of multiple transcriptional signaling pathways mediated by inducible transcription factors as well as nuclear hormone receptors.

3T3 Cells↗
PubMed1998

Oxidation of high density lipoproteins. I. Formation of methionine sulfoxide in apolipoproteins AI and AII is an early event that accompanies lipid peroxidation and can be enhanced by alpha-tocopherol.

The lipids of high density lipoproteins (HDL) are initially oxidized in preference to those in low density lipoprotein when human plasma is exposed to aqueous peroxyl radicals. In this work we report on the relative susceptibility of HDL protein and lipid to oxidation and on the role HDL's alpha-tocopherol (alpha-TOH) plays in modulating protein oxidation. Exposure of isolated HDL to either low fluxes of aqueous peroxyl radicals, Cu2+ ions, or soybean lipoxygenase resulted in the oxidation of apoAI and apoAII during the earliest stages of the reaction, i.e. after consumption of ubiquinol-10 and in the presence of alpha-TOH. Hydro(pero)xides of cholesteryl esters and phospholipids initially accumulated together with specific oxidized forms of apoAI and apoAII, separated by high pressure liquid chromatography. The specific oxidized forms of apoAI were 16 and 32 mass units heavier than those of the native apolipoproteins and contained 1 and 2 methionine sulfoxide residues per protein, respectively. The third methionine residue in apoAI, as well as Trp residues, remained unoxidized during the earliest stages of HDL oxidation examined. Exposure of isolated apoAI to peroxyl radicals, Cu2+, or soybean lipoxygenase resulted in nonspecific (for peroxyl radicals) or no discernible protein oxidation (Cu2+ and soybean lipoxygenase). This indicated that the formation of the specific oxidized forms of apoAI observed with native HDL was not the result of direct reaction of these oxidants with the apolipoprotein. In vitro and in vivo enrichment of HDL with alpha-TOH resulted in a dose-dependent increase in the extent of peroxyl radical-induced formation of HDL cholesteryl ester hydroperoxides (r = 0.96) and cholesteryl ester hydroxides (r = 0. 92), as well as the loss of apoAI (r = 0.96) and apoAII (r = 0.94). alpha-TOH enrichment also enhanced HDL lipid and protein oxidation induced by Cu2+ or soybean lipoxygenase. These results indicate that the earliest stages of HDL oxidation are accompanied by the oxidation of specific methionine residues in apoAI and apoAII and that in the absence of co-antioxidants, alpha-TOH can promote this process.

Amidines↗
PubMed1998

Oxidation of high density lipoproteins. II. Evidence for direct reduction of lipid hydroperoxides by methionine residues of apolipoproteins AI and AII.

Human high density lipoproteins (HDL) can reduce cholesteryl ester hydroperoxides to the corresponding hydroxides (Sattler W., Christison J. K., and Stocker, R. (1995) Free Radical Biol. & Med. 18, 421-429). Here we demonstrate that this reducing activity extended to hydroperoxides of phosphatidylcholine, was similar in HDL2 and HDL3, was independent of arylesterase and lecithin:cholesteryl acyltransferase activity, was unaffected by sulfhydryl reagents, and was expressed by reconstituted particles containing apoAI or apoAII only, as well as isolated human apoAI. Concomitant with the reduction of lipid hydroperoxides specific oxidized forms of apoAI and apoAII formed in blood-derived and reconstituted HDL. Similarly, specific oxidized forms of apoAI accumulated upon treatment of isolated apoAI with authentic cholesteryl linoleate hydroperoxide. These specific oxidized forms of apoAI and apoAII have been shown previously to contain Met sulfoxide (Met(O)) at Met residues and are also formed when HDL is exposed to Cu2+ or soybean lipoxygenase. Lipid hydroperoxide reduction and the associated formation of specific oxidized forms of apoAI and apoAII were inhibited by solubilizing HDL with SDS or by pretreatment of HDL with chloramine T. The inhibitory effect of chloramine T was dose-dependent and accompanied by the conversion of specific Met residues of apoAI and apoAII into Met(O). Canine HDL, which contains apoAI as the predominant apolipoprotein and which lacks the oxidation-sensitive Met residues Met112 and Met148, showed much weaker lipid hydroperoxide reducing activity and lower extents of formation of oxidized forms of apoAI than human HDL. We conclude that the oxidation of specific Met residues of apoAI and apoAII to Met(O) plays a significant role in the 2-electron reduction of hydroperoxides of cholesteryl esters and phosphatidylcholine associated with human HDL.

Acyltransferases↗
PubMed1998

Enhanced cholesterol efflux by tyrosyl radical-oxidized high density lipoprotein is mediated by apolipoprotein AI-AII heterodimers.

Myeloperoxidase secreted by phagocytes in the artery wall may be a catalyst for lipoprotein oxidation. High density lipoprotein (HDL) oxidized by peroxidase-generated tyrosyl radical has a markedly enhanced ability to deplete cultured cells of cholesterol. We have investigated the structural modifications in tyrosylated HDL responsible for this effect. Spherical reconstituted HDL (rHDL) containing the whole apolipoprotein (apo) fraction of tyrosylated HDL reproduced the ability of intact tyrosylated HDL to enhance cholesterol efflux from cholesterol-loaded human fibroblasts when reconstituted with the whole lipid fraction of either HDL or tyrosylated HDL. Free apoAI or apoAII showed no increased capacity to induce cholesterol efflux from cholesterol-loaded fibroblasts following oxidation by tyrosyl radical, either in their lipid-free forms or in rHDL. The product of oxidation of a mixture of apoAI and apoAII (1:1 molar ratio) by tyrosyl radical, however, reproduced the enhanced ability of tyrosylated HDL to induce cholesterol efflux when reconstituted with the whole lipid fraction of HDL. HDL containing only apoAI or apoAII showed no enhanced ability to promote cholesterol efflux following oxidation by tyrosyl radical, whereas HDL containing both apoAI and apoAII did. rHDL containing apoAI-apoAIImonomer and apoAI-(apoAII)2 heterodimers showed a markedly increased ability to prevent the accumulation of LDL-derived cholesterol mass by sterol-depleted fibroblasts compared with other apolipoprotein species of tyrosylated HDL. These results indicate a novel product of HDL oxidation, apoAI-apoAII heterodimers, with a markedly enhanced capacity to deplete cells of the regulatory pool of free cholesterol and total cholesterol mass. The recent observation of tyrosyl radical-oxidized LDL in vivo suggests that a similar modification of HDL would significantly enhance its ability to deplete peripheral cells of cholesterol in the first step of reverse cholesterol transport.

Apolipoprotein A-I↗
PubMedDate not supplied

Effect of female body weight on efficiency of donor AI.

A total of 1,144 infertile women were treated by artificial donor insemination. Unsuccessful ovulation induction was found in 96 of these cases. The obese women (BMI: 28-36) had a relative risk of unsuccessful ovulation induction of 2.7 (95% confidence interval (CI) = 2.1-3.4) compared with women lower or normal body weight (BMI: 20-24). The effect was smaller in women with a BMI 25-27 or < 19 (relative risk (RR) = 1.4, 95% CI = 0.9-2.1 and 1.5, 95% CI = 0.8-2.5), respectively. During the AID treatment 412 pregnancies occurred. Pregnancy rate achieved by insemination was 28% (50 pregnancies per 178 cases, BMI 16-19), 42% (251/599, BMI 20-24), 33% (92/286, BMI 25-27), and 21% (19/81, BMI 28-36), respectively, in the different BMI groups.

Body Mass Index↗
PubMed2005

The effect of group aerobic exercise and t'ai chi on functional outcomes and quality of life for persons living with acquired immunodeficiency syndrome.

OBJECTIVE: This study aimed to assess the usefulness of two interventions in a group rehabilitation medicine setting to determine strategies and exercise guidelines for long-term care of the HIV/AIDS population with human immunodeficiency virus (HIV) and/or acquired immunodeficiency syndrome (AIDS). DESIGN: This was a randomized clinical trial investigating the effects of tai chi (TC) and aerobic exercise (EX) on functional outcomes and quality of life (QOL) in patients with AIDS. SETTING: Two outpatient infectious disease clinics in a mid-atlantic state were the setting. SUBJECTS AND INTERVENTION: Thirty-eight (38) subjects with advanced HIV (AIDS) were randomized to one of three groups: TC, EX, or control. Experimental groups exercised twice weekly for 8 weeks. OUTCOME MEASURES: The primary outcomes included QOL as measured by the Medical Outcomes Short Form (MOS-HIV) and Spirituality Well-Being Scale (SWB). Functional measures included the functional reach (FR) for balance, sit and reach (SR) for flexibility, and sit-up (SU) test for endurance. The physical performance test (PPT) was used to determine overall function, and the Profile of Mood States (POMS) was used to evaluate psychologic changes. To consider the patients' explanations for these measurements, qualitative data were collected from subjects' journals, focus groups, and nonparticipant observation. RESULTS: Thirty-eight (38) subjects were included in data analysis: 13 in the TC group, 13 in the EX group, and 12 in the control group. Results of analysis of covariance showed significant changes in the exercise groups in overall functional measures (p < 0.001). The MOS-HIV showed a significant difference on the subscale of overall health (p = 0.04). The POMS showed significant main effect for time in confusion-bewilderment (p = 0.000) and tension-anxiety (p = 0.005). Three dominant themes emerged from the qualitative data, including: positive physical changes, enhanced psychologic coping, and improved social interactions. CONCLUSIONS: This study shows that TC and EX improve physiologic parameters, functional outcomes, and QOL. Group intervention provides a socialization context for management of chronic HIV disease. This study supports the need for more research investigating the effect of other types of group exercise for this population. This study sets the stage for a larger randomized controlled trial to examine the potential short- and long-term effects of group exercise that may prove beneficial in the management of advanced HIV disease. Further research is warranted to evaluate additional exercise interventions that are accessible, safe, and cost-effective for the HIV population.

Acquired Immunodeficiency Syndrome↗
PubMed2025

Effectidor II: a pan-genomic AI-based algorithm for the prediction of type III secretion system effectors.

MOTIVATION: Type III secretion systems are used by many Gram-negative bacteria to inject type 3 effectors (T3Es) directly into eukaryotic cells, promoting disease or provoking immune response. Because of these opposing evolutionary forces, T3E repertoires often vary within taxonomic groups. Identifying the full effector gene repertoire in genomes of related individuals is crucial for determining core and specialized effectors, understanding the disease dynamics, and developing appropriate management strategies against pathogens. It can also help uncover novel T3Es that have recently emerged in a population. Our previously published Effectidor web server successfully addressed the challenge of identifying T3Es in a single bacterial genome. Here, we enriched the web server with various novel capabilities, including the identification of T3Es from multiple genome sequences simultaneously. RESULTS: We present Effectidor II, a web server that relies on machine learning to predict T3E-encoding genes within bacterial pan-genomes. We demonstrate the benefit of learning based on features extracted from the entire sequences comprising the pan-genome and report a novel T3E discovered by it in Xanthomonas euroxanthea. AVAILABILITY AND IMPLEMENTATION: Effectidor II is available at: https://effectidor.tau.ac.il and the source code is available at: https://github.com/naamawagner/Effectidor. A stand-alone version of Effectidor II is available at: https://github.com/naamawagner/Effectidor/tree/StandAlone. The source code for the standalone version and the data used in this work are also provided in https://doi.org/10.5281/zenodo.15081636.

Type III Secretion Systems↗