Miracle-dz/UniFAR-FTUs huggingface dataset:
CXCR7/CXCR4 Heterodimer Constitutively Recruits β-Arrestin to Enhance Cell Migration*

G protein-coupled receptor hetero-oligomerization is emerging as an important regulator of ligand-dependent transmembrane signaling, but precisely how receptor heteromers affect receptor pharmacology remains largely unknown. In this study, we have attempted to identify the functional significance of the heteromeric complex between CXCR4 and CXCR7 chemokine receptors. We demonstrate that co-expression of CXCR7 with CXCR4 results in constitutive recruitment of β-arrestin to the CXCR4·CXCR7 complex and simultaneous impairment of Gi-mediated signaling. CXCR7/CXCR4 co-expression also results in potentiation of CXCL12 (SDF-1)-mediated downstream β-arrestin-dependent cell signaling pathways, including ERK1/2, p38 MAPK, and SAPK as judged from the results of experiments using siRNA knockdown to deplete β-arrestin. Interestingly, CXCR7/CXCR4 co-expression enhances cell migration in response to CXCL12 stimulation. Again, inhibition of β-arrestin using either siRNA knockdown or a dominant negative mutant abrogates the enhanced CXCL12-dependent migration of CXCR4/CXCR7-expressing cells. These results show how CXCR7, which cannot signal directly through G protein-linked pathways, can nevertheless affect cellular signaling networks by forming a heteromeric complex with CXCR4. The CXCR4·CXCR7 heterodimer complex recruits β-arrestin, resulting in preferential activation of β-arrestin-linked signaling pathways over canonical G protein pathways. CXCL12-dependent signaling of CXCR4 and its role in cellular physiology, including cancer metastasis, should be evaluated in the context of potential functional hetero-oligomerization with CXCR7.
Experimental Investigation of Parallel Connected YBCO Coated Conductors for Resistive Fault Current Limiters

Rapid development of the critical current density, homogeneity and the manufacturing process of commercially available YBCO coated conductors (CC) opens up new fields for power applications. The feasibility of superconducting fault current limiters (SCFCL) at medium and high voltage levels or for high current applications would be unimaginable without the concept of modular assembling. This means that CCs have to be connected in series according to voltage condition and in parallel according to specific current requirements to form the specific modules. The limiting behavior and the AC-losses of such a module can be defined by purposeful selecting components with different physical properties. This work presents the experimental results of a module of parallel connected CC with equal and different physical properties like stabilization and critical current (Ic). The tests are performed under different over-currents from minor overloads to fault currents and demonstrate the limiting behavior of a single CC and of the bundled CC in liquid nitrogen bath under ambient pressure.
Two daytime icodextrin exchanges decrease brain natriuretic peptide levels and improve cardiac functions in continuous ambulatory peritoneal dialysis patients

Aim: Peritoneal dialysis patients with ultrafiltration failure frequently have fluid overload. It is known that the increase in the ultrafiltration is associated with decrease in the left ventricle (LV) dysfunction. This study was designed to examine the potential effects of serum brain natriuretic peptide (BNP) on cardiac functions and to determine the relationship between BNP and cardiac parameters in continuous ambulatory peritoneal dialysis (CAPD) patients with ultrafiltration failure.
KEY SUCCESS FACTOR GOOD GOVERNMENT GOVERNANCE SERTA PENGARUHNYA TERHADAP KINERJA PEMERINTAH (Survey pada Pemerintah Kabupaten Gunungkidul)

In this era, local government performance in Indonesia is weak because there are many abuse of authority everywhere, like corruption, collusion, and nepotism. Each of local government should apply the principles of good government governance in the government environtment, this is to improve performnace of local government. In this research good government governance principle contain transparancy, accountability, residents particpation, fairness, and responsibility. The purpose of this research is analyze dan explain the empirical evidence about the influence of transparancy, accountability, residents participation, fairness, and responsibility to the performance of local government. This research use primary data. Primary data derived from quistionnaire which share to employee of local government in Gunungkidul. This research involve 100 sampleâ€™s. The sample is determined by Slovin sampling method. Sample in this research derived from the employee of local government and Gunungkidulâ€™s residents. Analitycal method use multiple regression. The result of this research is transparancy, accountability, and residents participation donâ€™t have influence to the performance of local government, but fairness and responsibility have a positive and significant influence to the performance of local government. Keyword: Good Government Governance, performance of local government.
Haplotypes at ATM identify coding-sequence variation and indicate a region of extensive linkage disequilibrium.

Genetic variation in the human population may lead to functional variants of genes that contribute to risk for common chronic diseases such as cancer. In an effort to detect such possible predisposing variants, we constructed haplotypes for a candidate gene and tested their efficacy in association studies. We developed haplotypes consisting of 14 biallelic neutral-sequence variants that span 142 kb of the ATM locus. ATM is the gene responsible for the autosomal recessive disease ataxia-telangiectasia (AT). These ATM noncoding single-nucleotide polymorphisms (SNPs) were genotyped in nine CEPH families (89 individuals) and in 260 DNA samples from four different ethnic origins. Analysis of these data with an expectation-maximization algorithm revealed 22 haplotypes at this locus, with three major haplotypes having frequencies > or = . 10. Tests for recombination and linkage disequilibrium (LD) show reduced recombination and extensive LD at the ATM locus, in all four ethnic groups studied. The most striking example was found in the study population of European ancestry, in which no evidence for recombination could be discerned. The potential of ATM haplotypes for detection of genetic variants through association studies was tested by analysis of 84 individuals carrying one of three ATM coding SNPs. Each coding SNP was detected by association with an ATM haplotype. We demonstrate that association studies with haplotypes for candidate genes have significant potential for the detection of genetic backgrounds that contribute to disease.
FK960 N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action.

With passive avoidance (PA), Morris water maze (WM) and eight-arm radial maze tasks, we evaluated the memory-enhancing action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a compound which we have found through rational drug screening based on our hypothesis that penile erection is a valid predictor of central cholinergic activation. Memory performance in the tasks was impaired in aged (24- to 26-months-old) rats as well as in rats with nucleus basalis magnocellularis lesions. Scopolamine (1 mg/kg i.p.) treatment induced memory impairment in PA and WM; treatment with cysteamine (200 mg/kg s.c.) induced memory impairment in PA but not in WM, whereas fimbria fornix lesioning affected the rats in the opposite manner. FK960 (0.1-10 mg/kg i.p.) ameliorated all the memory impairments except those induced by cysteamine or fimbria fornix lesion, and the dose-response curves were bell shaped with maximal response at 1 to 3.2 mg/kg. The effects of FK960 on the scopolamine-induced memory impairment in the PA and/or WM were abolished by cysteamine (200 mg/kg s.c.), dl-p-chlorophenylalanine methyl ester hydrochloride (150 mg/kg i.p. for 3 days) or raphe lesioning, but not by neonatal 6-hydroxydopamine (35 micrograms/head) treatment. Neurochemical analysis revealed that cysteamine and raphe lesions reduced brain somatostatin and serotonin contents, respectively. The treatment with FK960 (0.32-320 mg/kg p.o.) dose-dependently increased both serotonin and 5-hydroxyindoleacetic acid levels in the brain areas examined and significantly increased hippocampal somatostatin contents at the smaller doses. From these results, we conclude that FK960 ameliorates cognitive dysfunction through an activation of the somatostatinergic-serotonergic link.
Determinants of Virologic and Immunologic Outcomes in Chronically HIV-Infected Subjects Undergoing Repeated Treatment Interruptions: The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) Study

Background:Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated. Methods:In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm3, the rate of virologic failure, and the emergence of resistance at 24 months. Results:The proportion of subjects with a CD4 count >500 cells/mm3 was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm3 in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART). Conclusions:Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution.
Myofilament anchoring of protein kinase C-epsilon in cardiac myocytes

Regulatory proteins on muscle filaments are substrates for protein kinase C (PKC) but mechanisms underlying activation and translocation of PKC to this non-membrane compartment are poorly understood. Here we demonstrate that the epsilon isoform of PKC (ϵ-PKC) activated by arachidonic acid (AA) binds reversibly to cardiac myofibrils with an EC50 of 86 nM. Binding occurred near the Z-lines giving rise to a striated staining pattern. The delta isoform of PKC (δ-PKC) did not bind to cardiac myofibrils regardless of the activator used, and the alpha isoform (α-PKC) bound only under strong activating conditions. Three established PKC anchoring proteins, filamentous actin (F-actin), the LIM domain protein Cypher-1, and the coatamer protein β′-COP were each tested for their involvement in cytoskeletal anchoring. F-actin bound ϵ-PKC selectively over δ-PKC and α-PKC, but this interaction was readily distinguishable from cardiac myofilament binding in two ways. First, the F-actin/ϵ-PKC interaction was independent of PKC activation, and second, the synthetic hexapeptide LKKQET derived from the C1 region of ϵ-PKC effectively blocked ϵ-PKC binding to F-actin, but was without effect on its binding to cardiac myofilaments. Involvement of Cypher-1 was ruled out on the basis of its absence from detergent-skinned myofibrils that bound ϵ-PKC, despite its presence in intact cardiac myocytes. The ϵ-PKC translocation inhibitor peptide EAVSLKPT reduced activated ϵ-PKC binding to cardiac myofibrils in a concentration dependent manner, suggesting that a RACK2 or a similar protein plays a role in ϵ-PKC anchoring in cardiac myofilaments.
Morphogenese et systemes sexuels chez les isolats du genre armillaria d'afrique tropicale

Le travail a porte sur une soixantaine d'isolats armillaria (basidiomycete phytopathogene) originaires de 15 pays d'afrique tropicale et responsables du pourridie-agaric sur diverses plantes ligneuses. Nous avions deux objectifs principaux : 1) preciser la taxonomie des armillaires africaines. L'etude taxonomique a fait appel a differentes methodes : utilisation de la compatibilite somatique, etudes morphologiques et morphogenetiques (rhizomorphogenese, carpogenese, morphologie des thalles in vitro), etude des reaction des isolats a la temperature. 2) etudier les phenomenes sexuels et etablir le cycle caryologique des entites taxonomiques mises en evidence dans la premiere partie. Nous sommes parvenue a une classification des isolats en quatre groupes, dont deux correspondent a des especes deja decrites et deux pourraient etre des especes nouvelles. Le systeme sexuel a pu etre determine seulement pour les deux especes principale : #* a heimii comprend a la fois des isolats homothalliques et d'autres heterothalliques bipolaires, ce dernier systeme sexuel etant jusqu'ici inconnu chez les armillaires. L'heterothallisme bipolaire chez l'espece a. Heimii est accompagne d'allelomorphie multiple sur l'unique locus a d'incompatibilite sexuelle. Le phenomene de buller a ete mis en evidence chez a. Heimii, les haplontes des isolats heterothalliques peuvent egalement etre diploidises par des diplontes homothalliques, ce qui confirme l'unicite de l'espece. Les evenements a l'origine de ce phenomene sont plus frequemment lies au remplacement des noyaux de l'haplonte par ceux du diplonte compatible, plus rarement a des recombinaisons entre les noyaux de l'haplonte et du diplonte. #* a. Mellea a montre de nombreuses similitudes avec la meme espece rencontree en zone temperee. La principale difference dans le fait que l'espece africaine est homothallique alors l'espece europeenne est heterothallique tetrapolaire. A. Mellea d'afrique et d'europe ont ete considerees comme deux sous-especes. Deux types de cycle caryologique ont pu etre proposes : un cycle diplobiontique chez les epseces a. Mellea et quelques isolats de l'espece a. Heimii et un cycle haplo-diplobiontique chez certains isolats de l'espece a. Heimii heterothalliques bipolaires correspondant au cycle realise chez les especes europeennes a. Mellea sensustricto (in natura et in vitro) et a. Ostoyae in vitro.
Human Papillomavirus Infection: Low-Risk and High-Risk Genotypes in Women in Catania, Sicily

Introduction: Human papillomavirus (HPV) infection has been strongly and consistently associated with cervical carcinoma and its cytologic precursors, such as squamous intraepithelial lesions. A cross-sectional survey was conducted with the aim of estimating the prevalence of cervical HPV infection in women attending a service of colposcopy in Catania, Eastern Sicily, Italy. Methods: The prevalence of type-specific HPV was examined in women with negative colposcopic results and cervical intraepithelial neoplasia grades 1, 2, or 3, with the aim of providing some cross-sectional figures on the local epidemiology of HPV infection. Results: Human papillomavirus DNA was found in 62.1% of women with negative colposcopic results and in 73.2% with positive colposcopic results. Among high-risk types, a predominance of HPV-16 (51.5% of infected women) was shown followed by HPV-56 (29.7%). An age-related pattern was described with a peak in HPV prevalence among women younger than 25 years, followed by the expected decline in prevalence and a second characteristic peak in the perimenopausal or postmenopausal years, useful to design future control strategies. Conclusions: The age-related pattern of HPV prevalence and the presence of uncommon high-risk genotypes and their role in the pathogenesis of cervical cancer need to be addressed by specific epidemiologic studies to design large-scale screening programs and multivalent vaccine strategies.
Non‐human to human organ transplantation: Its biologic basis and a potential role for radiation therapy

There is an inadequate supply of human donor organs for transplantation. Xenotransplantation, the transplantation of organs from non‐human animals to humans, is one of the potential solutions to this problem. The pig appears to be the preferred donor. For xenotransplantation to be successful, researchers must deal with three fundamental problems: (1) Hyperacute rejection of porcine organs, related to binding of xenoreactive natural antibodies of the recipient to antigens on the graft's endothelial cells, must be overcome. (2) Transmission of animal pathogens to humans must be prevented. Concern about zoonosis is not only directed to the transplant recipient but also concerns the risk that an infectious agent will be transferred from the recipient to the general population. (3) The xenografted organ must be physiologically compatible with the recipient. The physiological function of a pig organ in a human and its ability to sustain a human are problematic. Total lymphoid irradiation (TLI) and thoraco‐abdominal irradiation (TAI) as immunosuppressive modalities have been investigated in rodent‐to‐rodent, large mammals and non‐human primates‐to‐primates, and pig‐to‐primate models. In certain clinical situations, TLI and TAI may prove to be important components for the preparation of the xenotransplant recipient. Progress in genetic engineering and cloning may soon lead to clinical trials in xenotransplantation. © 2001 Wiley‐Liss, Inc.
Functional architecture of the cortico‐basal ganglia circuitry during motor task execution: Correlations of strength of functional connectivity with neuropsychological task performance among female subjects

The primary aim of this study was to enhance our understanding of the functional architecture of the cortico‐basal ganglia circuitry during motor task execution. Twenty right‐handed female subjects without any history of neuropsychiatric illness underwent fMRI at 3 T. The activation paradigm was a complex motor task completed with the nondominant hand. Analyses of functional connectivity strength were conducted for pairs of structures in input, intrinsic, and output segments of the circuitry. Next, connectivity strengths were correlated with results of neurocognitive testing conducted outside of the scanner, which provided information about both motor and cognitive processes. For input pathways, results indicate that SMA–striatum interactions are particularly relevant for motor behavior and disruptions may impact both motor and cognitive functions. For intrinsic pathways, results indicate that thalamus (VA nucleus) to striatum feedback pathway appears to have an important role during task execution and carries information relevant for motor planning. Together, these findings add to accumulating evidence that the GPe may play a role in higher order basal ganglia processing. A potentially controversial finding was that strong functional connectivity appears to occur across intrinsic inhibitory pathways. Finally, output (thalamus to cortex) feedback was only correlated with motor planning. This result suggests circuit processes may be more relevant for future behaviors than the execution of the current task. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Prediction of response to pegylated interferon plus ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus.

BACKGROUND Variation in the IL28B gene is associated with sustained virologic response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)-monoinfected patients with genotype 1. Data on other genotypes and on patients coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We aimed to assess the predictive ability of variations in the single-nucleotide polymorphism rs12979860 for SVR in HIV/HCV-coinfected patients, regardless of HCV genotype. METHODS The rs12979860 genotype was determined by polymerase chain reaction in 154 patients who had received therapy against HCV with pegylated interferon plus ribavirin. RESULTS rs12979860 genotype was TT in 20 patients (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in patients with genotype CC and in those with genotype TC or TT, according to HCV genotype, were, respectively, 50% and 17% (P < .001) in patients with genotype 1, 80% and 25% (P = .027) in patients with genotype 4, and 93% and 77% (P = .115) in patients with genotype 3. The median (interquartile range) low-density lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73-120 mg/dL) versus 75 mg/dL (55-91 mg/dL) (P = .001) in those with TC or TT. Independent predictors of SVR were HCV genotype 2-3 (odds ratio [OR], 13.98; 95% confidence interval [CI], 4.87-40.1; P < .001), rs12979860 CC (OR, 5.05; 95% CI, 2.04-12.5; P < .001), baseline plasma HCV RNA load of < or =600,000 IU/mL (OR, 1.99; 95% CI, 1.18- 3.34; P = .009), and female sex (OR, 4.28; 95% CI, 1.08-16.96; P = .039). CONCLUSIONS IL28B gene variations independently predict SVR in HIV/HCV-coinfected patients with HCV genotype 1 and non-genotype 1 HCV infection. The association between rs12979860 and plasma low-density lipoprotein cholesterol suggests that the system low-density lipoprotein ligand/receptor might be involved in the effect of this genotype.
Fluvastatin inhibits up‐regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells

Summary. Background: Mechanisms of thrombosis induced by antiphospholipid (aPL) antibodies include up‐regulation of tissue factor (TF) expression on endothelial cells (ECs). Statins have been shown to reduce levels of TF induced by tumor necrosis factor (TNF‐α) and lipopolysaccharide (LPS) on ECs. In a recent study, fluvastatin inhibited thrombogenic and proinflammatory properties of aPL antibodies in in vivo models. The aim of this study was to determine whether fluvastatin has an effect on aPL‐induced expression of TF on ECs. Methods: IgGs were purified from four patients with APS (IgG‐APS) and from control sera (IgG‐NHS). Cultured human umbilical vein endothelial cells (HUVEC) were treated with IgG‐APS or IgG‐NHS or with medium alone or with phorbol myristate acetate (PMA), as a positive control. In some experiments, cells were pretreated with fluvastatin (2.5, 5 or 10 µm) with and without mevalonate (100 µm). TF expression on HUVECs was measured by ELISA. Results: PMA and the four IgG‐APS preparations increased the expression of TF on EC significantly (4.9‐, 2.4‐, 4.2‐, 3.5‐ and 3.1‐fold, respectively), in a dose‐dependent fashion. Fluvastatin (10 µm) inhibited the effects of PMA and the four IgG‐APS on TF expression by 70, 47, 65, 22 and 68%, respectively, and this effect was dose‐dependent. Mevalonate (100 µm) completely abrogated the inhibitory effects of fluvastatin on TF expression induced by aPL. Conclusion: Because of the suggested pathogenic role of aPL on induction of TF on ECs, our data provide a rationale for using statins as a therapeutic tool in treatment of thrombosis in APS.