Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Renin-Angiotensin Axis Inhibition on Early Atherogenesis in LDL-Receptor-Deficient Mice

Objective: The renin-angiotensin system may play a role in the development of atherosclerosis. Nevertheless, different results from studies attempting to attenuate the process by inhibiting the converting enzyme were equivocal, and in those who succeeded, blood pressure was lowered and/or the lipid profile was improved in addition to the inhibition of the renin-angiotensin axis. The aim of this study is to investigate the effect of low doses of fosinopril, a converting enzyme inhibitor, on the development of atherosclerosis in LDL-receptor-deficient mice. Methods: Three groups of 15 mice were fed a high-fat, high-cholesterol western diet. The three study groups received either distilled water (control group), or water supplemented with fosinopril 0.01 mg/kg/day (low-dose group) or with 0.1 mg/kg/day (high-dose group). Plasma aldosterone levels and lipid profiles were measured at the beginning and at the end of the study. After 10 weeks, the mice were sacrificed and the extent of atherosclerosis was assessed at the aortic sinus. Results: Plasma aldosterone levels did not change in the control group, but decreased significantly in both treated groups from 74.7 to 39.3 ng/ml in the low-dose group (p < 0.003) and from 70.7 to 33.6 ng/ml in the high-dose group (p < 0.001). The lipid profile at the end of the study showed significantly lower levels of cholesterol and triglycerides in the high-dose group as compared to the low-dose group (p < 0.05). There was no difference between the three groups regarding the area of atherosclerosis at the aortic sinus: 157,000 ± 34,000, 130,000 ± 58,000 and 145,000 ± 26,000 µm2 in the control, low-dose and high-dose groups, respectively. Conclusion: Inhibition of the renin-angiotensin-aldosterone axis by itself does not prevent the development of early atherosclerosis in LDL-receptor-deficient mice.
Protein, lipid and DNA repair systems in oxidative stress: the free-radical theory of aging revisited.

Aerobic organisms are constantly exposed to oxygen radicals and related oxidants. The antioxidant compounds and enzymes they have evolved remove most of the potentially damaging radicals/oxidants; however, damage to cellular proteins, lipids, nucleic acids and carbohydrates can be observed even under normal physiological conditions. Re-reduction of cellular components (direct repair) may be important for some biomolecules. In most cases studied to date, however, enzymatic degradation (by proteases, lipases, nucleases) appears to release damaged elements for excretion and conserve undamaged components for reutilization (indirect repair). In addition, the removal of damaged components appears to prevent or diminish the potential cytotoxicity of oxidized macromolecules. Several studies have reported an accumulation of oxidatively damaged cellular components with age (e.g., cataract formation, lipofuscin). Such reports are evidence that oxidant damage is one of several factors which contribute to the aging process, and provide at least partial support for the free-radical theory of aging. Studies of age-related changes in the activities, or levels of antioxidant enzymes and antioxidant compounds, however, have not provided complete understanding of the putative role of free radicals/oxidants in the aging process. In this review, we present the hypothesis that decreased activities or constitutive levels of oxidant repair enzymes may contribute to a progressive accumulation of oxidant damage with aging. Furthermore, the ability to mount an effective response to oxidative stress (induction of oxidant stress genes and proteins) may decline with age, thus predisposing older cells and organisms to oxidant damage.
Cleavage, methylation, and localization of the Pseudomonas aeruginosa export proteins XcpT, -U, -V, and -W

Four components of the apparatus of extracellular protein secretion of Pseudomonas aeruginosa, Xcpt, -U, -V, and -W (XcpT-W), are synthesized as precursors with short N-terminal leader peptides that share sequence similarity with the pilin subunit of this organism. A specialized leader peptidase/methylase, product of the pilD gene, has been shown to cleave the leader peptide from prepilin and to methylate the N-terminal phenylalanine of the mature pilin. Antibodies were prepared against XcpT-W and used to purify each of these proteins. Sequence analysis of XcpT-W has shown that these proteins, like mature pilin, contain N-methylphenylalanine as the N-terminal amino acid. Analysis of cellular fractions from wild-type and pilD mutant strains of P. aeruginosa showed that the precursor forms of XcpT-W are located predominantly in the bacterial inner membrane, and their localization is not altered after PilD-mediated removal of the leader sequence. These studies demonstrate that the biogenesis of the apparatus of extracellular protein secretion and that of type IV pili share a requirement for PilD. This bifunctional enzyme, acting in the inner membrane, cleaves the leader peptides from precursors of pilins and XcpT-W and subsequently methylates the amino group of the N-terminal phenylalanine of each of its substrates.
Pre-shot EEG alpha-power reactivity during expert air-pistol shooting: A comparison of best and worst shots

The aim of this study was to examine the proposal that pre-shot occipital electroencephalogram (EEG) alphapower reactivity would not only associate with, but also have a causal role in, the relative success of performance outcome in expert air-pistol shooting. Six expert air-pistol shooters performed a sixty-shot match, individually, while electroencephalograms were captured from occipital and anterior-temporal electrode sites during the aiming period (3 2 2 s epochs) before shot release. The five best shots and five worst shots were selected for each shooter on the basis of four shot quality indicators, and pre-shot EEG alpha power for best shots was compared with that of worst shots. Occipital EEG alpha power was found to increase during epochs 1–3 before best shots, but to decrease before worst shots; it was significantly greater during the final pre-shot epoch of best shots. This finding suggests that visual attention to the pistol and target was gradually suppressed during the pre-shot period of best shots, whereas it gradually increased before worst shots. In addition, significantly greater EEG alpha power was found at the left than at the right anterior-temporal site, lending support to the robust findings of previous target-sport studies. We conclude that the participants were able to shoot at the target with greatest success when not having maximal visual attention on where the pistol was aimed and that suppression of visual attention during the final seconds of the pre-shot period is a necessary prerequisite for automatic shot execution, as controlled by mechanisms of intention.
Sport-for-All Policy in Taiwan: a case of ongoing change?

This study analyses the extent of Taiwan's sport-for-all policy change during the policy-making and delivery process of the Sports Island Plan. Indicators of policy change including organization, legal framework and budget (Hogwood & Peters, 1983) were used to measure the degree to which the policy had changed. In addition to the analysis of official documents, 16 interviews with stakeholders of the Sports Island Plan were conducted from 2012 to 2014. Interviewees included legislators, officials from both central and local government and scholars involved in the policy-making process. The results revealed that while there had been significant changes in organization and budget, the perceptions of certain interviewees indicated problems in both design and delivery. Further analysis showed that the Sports Island Plan has not successfully addressed the shortcomings of Taiwan's sport-for-all policy. This suggests that future policies should take more account of local sports organizations.
Compact Circularly Polarized Archimedean Spiral Antenna for Ultrawideband Communication Applications

A novel compact circularly polarized Archimedean spiral antenna for ultrawideband (UWB) communication applications is presented. The basic structure is a two-arm planar Archimedean spiral antenna, which is fed by a tapered wideband balun. These two arms are extended on the profile and connected together at the end to elongate current path, while four lumped resistors are loaded on them to improve the reflection coefficient at low frequency. A circular reflector with cross slots that consists of one circular slot at the junction of two orthogonal rectangular slots are designed and optimized, which improves the performance of axial ratio (AR). The proposed antenna has a compact size of 36 × 36 × 20 mm3. The voltage standing-wave ratio is less than 2.5 in the frequency range of 1.9–8.5 GHz and the AR is less than 3 dB in the frequency range of 2–6 GHz. Both the simulation and measurement results are presented, demonstrating the UWB characteristics of the proposed antenna for wireless communication applications.
Immunopathogenesis of primary Sjögren's syndrome: implications for disease management and therapy

Purpose of reviewRecent studies have broadened our understanding of the etiopathogenesis and immunopathology of primary Sjögren's syndrome. This review highlights recent advances in understanding the underlying mechanisms of the disease as well as their implications for clinical handling and therapeutic options. Recent findingsIt becomes increasingly apparent that certain disturbances of the immune system (i.e. B-cell hyperreactivity and enhanced levels of B-cell-activating factor/B-lymphocyte stimulator) play a central role in this entity. Whether this is a primary abnormality or the result of predisposing factors or infectious, e.g. viral, agents remains uncertain. New insights into the pathogenesis also provide candidates for better diagnosis and classification of disease severity, such as flow cytometric analysis, measurement of soluble cell surface molecules, autoantibodies, cytokines, and ligands (B-cell-activating factor/B-lymphocyte stimulator). Whether B-cell-directed therapies (i.e. blocking B-cell-activating factor/B-lymphocyte stimulator, anti-CD20 therapy) will have an impact on primary Sjögren's syndrome needs to be shown in clinical trials. Alternative therapeutic approaches such as organ-targeted gene transfer are in development but must be carefully evaluated for safety and efficacy in preclinical models that resemble human primary Sjögren's syndrome. SummaryThe pathogenesis of primary Sjögren's syndrome is complex and the factors initiating and driving autoimmunity in this entity are largely unknown. Recent studies provide new insights into potential pathogenetic mechanisms of the disease and, thereby, the chance for improved strategies in disease management and therapy.
Distinction in gene expression profiles demonstrated in parathyroid adenomas by high-density oligoarray technology.

OBJECTIVES Somatic deletion of chromosome 11q13 is the most frequent genetic aberration in parathyroid adenoma. To gain further insight into the genetic etiology of parathyroid tumor development, we examined a comprehensive gene expression profile of parathyroid adenomas and normal parathyroid tissues. The results were then evaluated with respect to differences between adenomas and normal parathyroid tissue, and to the presence of loss of heterozygosity (LOH) in chromosomal region 11q13. DESIGN AND METHODS Sporadic parathyroid adenomas and normal parathyroids were hybridized against HG-U95Av2 oligonucleotide arrays (Affymetrix) containing a total of 12,625 probe sets. Quantitative real-time PCR (QRT-PCR) was performed in a larger series of parathyroid adenomas, in order to con-firm the microarray results. RESULTS Cyclin D1 and c-Jun showed increased expression in adenomas vs normal parathyroids by microarray analysis and QRT-PCR, suggesting an oncogenic role of these genes in parathyroid tumor development. At unsupervised hierarchical clustering, the adenomas fell into two groups: Group I adenomas were characterized by 11q13 LOH, while Group II adenomas lacked this abnormality. In addition, a t-test analysis identified largely non-overlapping genes with differential expression in the tumors subgroups; e.g. in Group I tumors the putative oncogene ENC 1 was found highly over-expressed vs Group II adenomas. CONCLUSIONS The microarray analyses revealed partly distinctive and partly common expression profiles in parathyroid adenomas with and without 11q13 LOH. In addition, approximately half of the under-expressed genes were mapped to chromosome 11, in agreement with a dose effect following loss of this chromosome.
Effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance of overweight women.

BACKGROUND Omentin, chemerin and vaspin are novel adipokines that are secreted from adipose tissue and improved insulin sensitive. The purpose of this study was to examine the effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance (IR) of overweight women. METHODS Forty aged healthy women (age; 25-45 years old, waist circumference [WC]>88 cm; Body Mass Index (BMI)>25 kg/m2) were selected purposely and divided in two control (N.=16) and experimental (N.=19) groups. Five dropped out during the study. The experimental group trained 12 weeks (3 sessions per week, one hr/session). The exercise program consisted of rhythmic aerobic exercise (55-85% maximum heart rate) along with core stability training. Serum chemerin, omentin, vaspin and insulin concentration were assayed by commercially ELISA kit. IR was evaluated according to the Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR). Data were analyzed by dependent and independent t-test to compare pre-test and post-test in each group and to compare the amount of changes in experimental and control training groups after twelve weeks. RESULTS The result showed that exercise training had significant effect on BMI (P=0.00), WC (P=0.00), body fat (P=0.05), chemerin (P=0.041) and vaspin (P=0.045). But, this training had non-significant effect on plasma omentin level (P=0.090), plasma glucose level (P=0.670), insulin (P=0.11) and IR (P=0.07). CONCLUSIONS Despite the fact that this kind of intervention could be an effective treatment to improve some adipokine levels and was accompanied by decreased body fat and waist circumference. However, more intense training is required to significantly change IR and serum omentin level in overweight women.
A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects.

ACE910 is a recombinant humanized bispecific antibody that binds to activated factor IX and factor X and mimics the cofactor function of factor VIII (FVIII). This first-in-human study examined the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ACE910 in healthy male adults. A total of 40 Japanese and 24 white subjects were randomized to receive a single subcutaneous injection of ACE910 (Japanese: 0.001, 0.01, 0.1, 0.3, or 1 mg/kg; white: 0.1, 0.3, or 1 mg/kg; n = 6 per dose group) or placebo (n = 2 per dose group). ACE910 exhibited a linear PK profile and had a half-life of ∼4 to 5 weeks. In FVIII-neutralized plasma, ACE910 shortened activated partial thromboplastin time and increased peak height of thrombin generation in a dose-dependent manner. All adverse events were nonserious and did not lead to any subject's withdrawal. Neither clinical findings nor laboratory abnormalities indicating hypercoagulability were observed. Two of 48 subjects receiving ACE910 (1 Japanese and 1 white) were positive for anti-ACE910 antibodies (anti-drug antibodies [ADAs]). One subject tested positive for ADAs both before and after ACE910 administration, whereas the other became ADA positive after receiving ACE910. The PK and PD profiles of ACE910 were similar in healthy Japanese and white subjects and suggest that ACE910 will be an effective and convenient prophylactic treatment of hemophilia A. This trial was registered at www.clinicaltrials. jp as #JapicCTI-121934.
Ginger Ingredients Alleviate Diabetic Prostatic Complications: Effect on Oxidative Stress and Fibrosis

Prostatic complications are common in patients with diabetes. This study investigated the effect of different ginger ingredients: zingerone, geraniol, and 6-gingerol on the prostate in diabetic rats. Diabetes was induced in Wistar rats by streptozotocin intraperitoneal injection (50 mg/kg), and the rats were left for 10 weeks to develop prostatic complications. In diabetic treated groups, rats received daily oral zingerone, geraniol, and 6-gingerol in doses of 20, 200, and 75 mg/kg, respectively, in the last 8 weeks. Treatment with the compounds caused changes in the ventral prostate of diabetic animals as indicated by the columnar ductal epithelium and dense secretions. There was an amelioration of oxidative stress as evidenced by the lowering of prostate malondialdehyde and elevating prostate oxidized to reduced glutathione (GSH/GSSG) ratios by geraniol and 6-gingerol. None of the three ginger ingredients affected the hyperglycemia, reduction in body weight gain, and testosterone deficiency seen in diabetic animals. Interleukin-1β and interleukin-6 levels remained unchanged. However, zingerone and geraniol ameliorated the fibrosis in diabetic prostate through suppressing the elevated prostate transforming growth factor beta 1 (TGFβ1) and collagen IV. Therefore, ginger ingredients could be beneficial in alleviating diabetic prostatic complications through suppressing oxidative stress and tissue fibrosis.
El aprendizaje cooperativo y el desarrollo de competencias con la experiencia de la multiculturalidad

Resumen El aprendizaje cooperativo y las metodologias aplicadas en las actividades de estudio grupales se muestran como un elemento esencial en el desarrollo de competencias del alumno en el marco del Espacio Europeo de Educacion Superior. A traves de la presente comunicacion, se aportan determinados metodos complementarios del trabajo grupal, poniendo especial enfasis en el aprovechamiento de la diversidad cultural. Para ello, se toma como referencia la experiencia en asignaturas como Economia Agraria, impartida actualmente en la titulacion de LADE de la Universidad de Almeria, donde la creciente incorporacion de alumnos procedentes de familias inmigrantes y la consiguiente multiculturalidad implican un valor anadido para la consecucion de diversas competencias. A partir de la aplicacion de estos metodos, se observan actitudes para contextualizar los hechos economicos con una vision internacional mas real, asi como la mejora de la capacidad analitica del estudiante para abordar problemas economicos desde diferentes perspectivas.
Identification of noninvasive imaging surrogates for brain tumor gene-expression modules

Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. We combined neuroimaging and DNA microarray analysis to create a multidimensional map of gene-expression patterns in GBM that provided clinically relevant insights into tumor biology. Tumor contrast enhancement and mass effect predicted activation of specific hypoxia and proliferation gene-expression programs, respectively. Overexpression of EGFR, a receptor tyrosine kinase and potential therapeutic target, was also directly inferred by neuroimaging and was validated in an independent set of tumors by immunohistochemistry. Furthermore, imaging provided insights into the intratumoral distribution of gene-expression patterns within GBM. Most notably, an “infiltrative” imaging phenotype was identified that predicted patient outcome. Patients with this imaging phenotype had a greater tendency toward having multiple tumor foci and demonstrated significantly shorter survival than their counterparts. Our findings provide an in vivo portrait of genome-wide gene expression in GBM and offer a potential strategy for noninvasively selecting patients who may be candidates for individualized therapies.
Sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and calsequestrin are overexpressed in spared intrinsic laryngeal muscles of dystrophin‐deficient mdx mice

In the mdx mouse model of Duchenne muscular dystrophy, the lack of dystrophin is associated with increased calcium levels and skeletal muscle myonecrosis. The intrinsic laryngeal muscles (ILM) are protected and do not undergo myonecrosis. We investigated whether this protection is related to an increased expression of calcium‐binding proteins, which may protect against the elevated calcium levels seen in dystrophic fibers. The expression of sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and calsequestrin was examined in ILM and in nonspared limb muscles of control and mdx mice using immunofluorescence and immunoblotting. Dystrophic ILM presented a significant increase in the proteins studied when compared to controls. The increase of Ca2+‐handling proteins in dystrophic ILM may permit better maintenance of calcium homeostasis, with the consequent absence of myonecrosis. The results further support the concept that abnormal Ca2+‐handling is involved in dystrophinopathies. Muscle Nerve, 2009
MgrA Is a Multiple Regulator of Two New Efflux Pumps in Staphylococcus aureus

ABSTRACT In an analysis of the resistance mechanisms of an mgrA mutant, we identified two genes encoding previously undescribed transporters, NorB and Tet38. norB was 1,392 bp and encoded a predicted 49-kDa protein. When overexpressed, NorB led to an increase in resistance to hydrophilic quinolones, ethidium bromide, and cetrimide and also to sparfloxacin, moxifloxacin, and tetracycline, a resistance phenotype of the mgrA mutant. NorA and NorB shared 30% similarity, and NorB shared 30 and 41% similarities with the Bmr and Blt transporters of Bacillus subtilis, respectively. The second efflux pump was a more selective transporter that we have called Tet38, which had 46% similarity with the plasmid-encoded TetK efflux transporter of S. aureus. tet38 was 1,353 bp and encoded a predicted 49-kDa protein. Overexpression of tet38 produced resistance to tetracycline but not to minocycline and other drugs. norB and tet38 transcription was negatively regulated by MgrA. Limited binding of MgrA to the promoter regions of norB and tet38 was demonstrated by gel shift assays, suggesting that MgrA was an indirect regulator of norB and tet38 expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain. These data demonstrate that overexpression of NorB and Tet38 contribute, respectively, to the hydrophobic quinolone resistance and the tetracycline resistance of the mgrA mutant and that MgrA regulates expression of norB and tet38 in addition to its role in regulation of norA expression.