Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of insulin-like growth factor (IGF)-I/IGF-binding protein-3 treatment on glucose metabolism and fat distribution in human immunodeficiency virus-infected patients with abdominal obesity and insulin resistance.

CONTEXT HIV-infected patients on antiretroviral therapy are at increased risk for excess visceral adiposity and insulin resistance. Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals. OBJECTIVE Our objective was to determine whether IGF-I, complexed to its major binding protein, IGF-binding protein-3 (IGFBP-3), improves glucose metabolism and alters body fat distribution in HIV-infected patients with abdominal obesity and insulin resistance. METHODS We conducted a pilot, open-label study in 13 HIV-infected men with excess abdominal adiposity and insulin resistance to assess the effect of 3 months of treatment with IGF-I/IGFBP-3 on glucose metabolism and fat distribution. Glucose metabolism was assessed by oral glucose tolerance test and hyperinsulinemic-euglycemic clamp. Endogenous glucose production (EGP), gluconeogenesis, whole-body lipolysis, and de novo lipogenesis (DNL) were measured with stable isotope infusions. Body composition was assessed by dual-energy x-ray absorptiometry and abdominal computed tomography scan. RESULTS Glucose tolerance improved and insulin-mediated glucose uptake increased significantly during treatment. EGP increased under fasting conditions, and suppression of EGP by insulin was blunted. Fasting triglycerides decreased significantly in association with a decrease in hepatic DNL. Lean body mass increased and total body fat decreased, whereas visceral adipose tissue did not change. CONCLUSIONS Treatment with IGF-I/IGFBP-3 improved whole-body glucose uptake and glucose tolerance, while increasing hepatic glucose production. Fasting triglycerides improved, reflecting decreased DNL, and visceral adiposity was unchanged.
Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells

Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons, raising the question of whether they interact during Renshaw cell development. In other well‐studied neurons, such as Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (ER81−/− knockout), weakened (Egr3−/− knockout), or strengthened (mlcNT3+/− transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their deselection and reduces motor axon synaptic density, and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells. J. Comp. Neurol. 524:1892–1919, 2016. © 2016 Wiley Periodicals, Inc.
Variability in the language input to children enhances learning in a treatment context.

PURPOSE Artificial language learning studies have demonstrated that learners exposed to many different nonword combinations representing a grammatical form demonstrate rapid learning of that form without explicit instruction. However, learners presented with few exemplars, even when they are repeated frequently, fail to learn the underlying grammar. This study translated this experimental finding in a therapeutic context. METHOD Eighteen preschool children with language impairment received conversational recast treatment for morpheme errors. Over a 6-week period, half heard 12 unique verbs twice each during recasts (low-variability condition), and half heard 24 unique verbs (high-variability condition). Children's use of trained and untrained morphemes on generalization probes as well as spontaneous use of trained morphemes was tracked throughout treatment. RESULTS The high-variability condition only produced significant change in children's use of trained morphemes, but not untrained morphemes. Data from individual children confirmed that more children in the high- than the low-variability condition showed a strong treatment effect. Children in the high-variability condition also produced significantly more unique utterances containing their trained morpheme than children in the low-variability condition. CONCLUSION The results support the use of highly variable input in a therapeutic context to facilitate grammatical morpheme learning.
Characterization of C3a receptor‐proteins on guinea pig platelets and human polymorphonuclear leukocytes

The expression of specific membrane receptors for C3a was determined on guinea pig C3a‐sensitive (gp R+) platelets and human polymorphonuclear leukocytes (hu PMNL). Binding studies with 125I‐labeled C3a from gp or hu sources and Scatchard analysis applied to the binding data revealed the existence of two receptor classes on gp R+ platelets; a high‐affinity class with about 200 binding sites/cell and Kd = 1.7 x 10−9 M, and a relatively low‐affinity class with Kd = 10−8 M and about 500 sites/cell. Hu PMNL express a homogeneous receptor class with Kd = 3 x 10−8 M and 40000 sites/cell. Molecular characterization of the C3a receptor on gp R+ platelets was achieved by (a) cross‐linking photoaffinity‐labeled receptors to bound 125I‐labeled C3a; (b) photoaffinity labeling receptors with a 13‐amino acid residue C3a analogue 125I‐Nap‐Ahx‐13; and (c) use of chemical cross‐linkers like disuccinimidylsuberate to cross‐link receptors with 125I‐C3a. All three techniques gave rise to very similar labeling patterns. With the photoaffinity labeling methods, a diffuse band pattern was observed with an apparent molecular mass of 95–123 kDa with 125I‐C3a as label, and 85–105 kDa with 125I‐Nap‐Ahx‐13 as label. Chemical cross‐linking of 125I‐C3a revealed three distinct bands with molecular masses of approximately 123, 108 and 95 kDa. Subtracting the contribution of the cross‐linked ligands, the C3a receptor on gp R+ platelets appears to be a protein complex, consisting of one to three components with estimated molecular masses between 83–114 kDa.
Imaging the pre‐ and postsynaptic side of striatal dopaminergic synapses in idiopathic cervical dystonia: A SPECT STUDY Using [123I] epidepride and [123I] β‐CIT

There is increasing evidence that a dysfunction of the dopaminergic system may be involved in the pathogenesis of idiopathic dystonia. To visualize possible alterations of the pre‐ and postsynaptic side of striatal dopaminergic synapses, SPECT studies using the radiotracers [123I] epidepride and [123I] β‐CIT were performed in 10 patients with idiopathic cervical dystonia. Eleven age‐ and sex‐matched subjects served as controls. [123I] Epidepride is a new highly affine marker of D2 receptors, and [123I] β‐CIT binds to dopamine transporters on dopaminergic nerve endings. [123I] Epidepride binding was significantly reduced in both striata of dystonia patients compared with controls (p < 0.05). In contrast, striatal [123I] β‐CIT uptake did not differ from controls. We conclude that dopaminergic dysfunction in idiopathic focal dystonia mainly involves postsynaptic mechanisms and suggest a disturbance of the indirect pathway of the motor circuit resulting in a disinhibited thalamocortical stimulation.
Diverse Myeloid and Lymphoid Cell Subpopulations Produce Gamma Interferon during Early Innate Immune Responses to Francisella tularensis Live Vaccine Strain

ABSTRACT Francisella tularensis, a small gram-negative intracellular bacterium responsible for causing tularemia, is highly pathogenic and classified as a category A agent of bioterrorism. As for other intracellular pathogens, successful protective immune responses to Francisella tularensis require rapid and efficient induction of gamma interferon (IFN-γ) production. Studies using intracellular bacteria such as Listeria monocytogenes as well as Francisella suggest that natural killer (NK) and T cells are important sources of IFN-γ. However, comprehensive characterization of specific sources of IFN-γ produced during Francisella infection in vivo remains incomplete, and depletion of NK cells before infection of mice with the F. tularensis live vaccine strain (LVS) has little impact on the course or outcome of infection. In this study, we determined the cell subpopulations that respond quickly to intradermal F. tularensis LVS infection of mice by producing IFN-γ within hours to a few days. Splenic and liver lymphocytes were obtained from LVS-infected mice and analyzed for IFN-γ mRNA by reverse transcription-PCR, for intracellular cytokine expression by multiparameter flow cytometry, and for ex vivo production of IFN-γ protein by enzyme-linked immunosorbent assay. Cells producing IFN-γ were readily detectable by day 3 after infection, and numbers progressively increased through days 5 to 7. Importantly, the cell types responsible for IFN-γ production were much more varied than expected: these included not only NK cells and T cells, which might be predicted, but also other cells, including dendritic cells (DCs), “NK DCs,” NK T cells, and neutrophils. Most importantly, since RAG-1 knockout mice appeared to exhibit a frequency of IFN-γ-producing cells comparable to that of intact wild-type mice, early IFN-γ production by innate immune cells does not depend on the presence of T or B cells.
Pravastatin modulates cholesteryl ester transfer from HDL to apoB-containing lipoproteins and lipoprotein subspecies profile in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) results from genetic defects in the LDL receptor, and is characterized by a marked elevation in plasma LDL and by qualitative abnormalities in LDL particles. Because LDL particles are major acceptors of cholesteryl esters (CEs) from HDL, significant changes occur in the flux of CE through the reverse cholesterol pathway. To evaluate the effects of an HMG-CoA reductase inhibitor, pravastatin, on CE transfer from HDL to apo B-containing lipoproteins and on plasma lipoprotein subspecies profile in subjects with heterozygous FH, we investigated the transfer of HDL-CE to LDL subfractions and changes in both concentration and chemical composition of the apo B- and the apo AI-containing lipoproteins. After pravastatin treatment (40 mg/d) for a 12-week period, plasma LDL concentrations (mean +/- SD, 745.4 +/- 51.9 mg/dL) were reduced by 36% in patients with FH (n = 6). By contrast, the qualitative features of the density profile of LDL subspecies in patients with FH, in whom the intermediate (d = 1.029 to 1.039 g/mL) and dense (d = 1.039 to 1.063 g/mL) subspecies were significantly increased relative to a control group, were not modified by pravastatin. In addition, no significant effect on the chemical composition of individual LDL subfractions was observed. Furthermore, plasma HDL concentrations were not modified, although the density distribution of HDL was normalized. Indeed, the HDL density peak was shifted towards the HDL2 subfraction (ratios of HDL2 to HDL3 were 0.7 and 1.1 before and after treatment, respectively). Evaluation of plasma CE transfer protein (CETP) mass was performed with an exogenous CE transfer assay. Under these conditions, no modification of plasma CETP protein mass was induced by pravastatin administration. However, the rate of CE transfer from HDL to LDL was reduced by 24% by pravastatin (61 +/- 17 micrograms CE.h-1.mL-1 plasma; P < .0005), although intermediate and dense LDL subfractions again accounted for the majority (71%) of the total CE transferred to LDL. Thus, pravastatin induced reduction of plasma CETP activity without change in the preferential targeting of the transfer of HDL-CE towards the denser LDL subfractions. In conclusion, pravastatin reduces the elevated flux of CE from HDL to apo B-containing lipoproteins in subjects with heterozygous FH as a result of a reduction in the LDL particle acceptor concentration.
Possible Involvement of Calpain Activation in Pathogenesis of Chronic Heart Failure After Acute Myocardial Infarction

Changes in proteolytic activity of the myocardium during the development of heart failure after left coronary artery ligation (CAL) of rats were examined. Hemodynamics of the rats at the eighth week (8w-CAL rat), but not at the second week (2w-CAL rat), after CAL showed the symptoms of chronic heart failure. Contents of μ-calpin and m-calpain, but not an intrinsic calpain inhibitor calpastatin, in the viable left ventricular muscle (viable LV) and the right ventricular muscle (RV) of the 2w-CAL and 8w-CAL rats were increased, which was associated with an elevation of intrinsic activities of leupeptin-sensitive, Ca2+-activated proteolysis in the cytosolic fractions of the viable LV and RV. Oral administration of 3 mg/kg/d trandolapril or 1 mg/kg/d candesartan from the second to eighth week after CAL improved the hemodynamics of 8w-CAL rats. The drug treatment attenuated the increases in μ-calpain and m-calpain contents and the elevation of the proteolytic activity of the viable LV and RV in the 8w-CAL rat. The drug treatment increased calpastatin content of the RV in the 8w-CAL rat. These results suggest that sustained activation of calpain is involved in the development of chronic heart failure and that trandolapril and candesartan prevent the activation of calpains after CAL.
Functional morphology of the forelimb of Tupaiids (Mammalia, Scandentia) and its phylogenetic implications

In this study, the forelimb of 12 species of tupaiids was analyzed functionally and compared to that of other archontan mammals. Several differences that relate to differential substrate use were found in the forelimb morphology of tupaiids. These differences included shape of the scapula, length and orientation of the coracoid process, size of the lesser tuberosity, shape of the capitulum, length of the olecranon process, and shape of the radial head and central fossa. The forelimb of the arboreal Ptilocercus lowii, the only ptilocercine, is better adapted for arboreal locomotion, while that of tupaiines is better adapted for terrestrial (or scansorial) locomotion. While the forelimb of the arboreal Ptilocercus appears to be habitually flexed and exhibits more mobility in its joints, a necessity for movement on uneven, discontinuous arboreal supports, all tupaiines are characterized by more extended forelimbs and less mobility in their joints. These restricted joints limit movements more to the parasagittal plane, which increases the efficiency of locomotion on a more even and continuous surface like the ground. Even the most arboreal tupaiines remain similar to their terrestrial relatives in their forelimb morphology, which probably reflects the terrestrial ancestry of Tupaiinae (but not Tupaiidae). The forelimb of Urogale everetti is unique among tupaiines in that it exhibits adaptations for scratch‐digging. Several features of the tupaiid forelimb reflect the arboreal ancestry of Tupaiidae and it is proposed that the ancestral tupaiid was arboreal like Ptilocercus. Also, compared to the forelimb character states of tupaiines, those of Ptilocercus are more similar to those of other archontans and it is proposed that the attributes of the forelimb of Ptilocercus are primitive for the Tupaiidae. Hence, Ptilocercus should be considered in any phylogenetic analysis that includes Scandentia. J. Morphol. 253:10–42, 2002. © 2002 Wiley‐Liss, Inc.
The PTPN22*R620W polymorphism does not confer genetic susceptibility to antiphospholipid syndrome in the Spanish population

In this work, we proposed to determine the association of the PTPN22*R620W SNP with primary antiphospholipid syndrome (PAPS) in a case–control association study of Spanish Caucasian individuals. A total of 81 PAPS patients were compared with 81 blood‐donor healthy control subjects. PTPN22 SNP (R620W) genotyping was performed by using a polymerase chain reaction–restricted fragment length polymorphism assay. No statistically significant differences were found between control subjects and PAPS patients for the PTPN22*R620W genotypes (P = 0.214). No statistically significant differences were found according to either the presence or absence of antiphospholipid antibodies or the clinical manifestations associated to PAPS. Our results indicate that this functional PTPN22*R620W polymorphism is not associated to PAPS; it seems not to be a risk factor in our Spanish population. The effect of the PTPN22 SNP on clinical manifestations and presence of antiphospholipid antibodies in APS warrants further investigations.
Ototoxicity from high‐dose use of platinum compounds in patients with neuroblastoma

The young age of neuroblastoma patients makes them especially prone to the ototoxic effects of widely used treatments that feature aggressive use of platinum compounds. We present data defining the extent of the problem in a large series of neuroblastoma patients whose induction included high‐dose cisplatin/etoposide (HD‐P/E) as used in both the Memorial Sloan‐Kettering Cancer Center N7 regimen and the Children's Oncology Group A3973 study.
Multilevel Analysis of the Relationship Between Type of Travel, Online Ratings, and Management Response: Empirical Evidence from International Upscale Hotels

ABSTRACT The diverse characteristics of customers and hotels have been identified as relevant to online customer satisfaction at the individual level. In this study, a comprehensive examination is conducted, through the use of a multilevel, nested model and secondary data set. The results show that both online review experience and management response frequencies can positively affect customer satisfaction. Additionally, hotel managers need to pay more attention to customers who have less online review experience when they carry out targeted response strategies. The findings have various implications for both academic researchers and hotel operators.
The origin and evolution of Archaea: a state of the art

Environmental surveys indicate that the Archaea are diverse and abundant not only in extreme environments, but also in soil, oceans and freshwater, where they may fulfil a key role in the biogeochemical cycles of the planet. Archaea display unique capacities, such as methanogenesis and survival at temperatures higher than 90 °C, that make them crucial for understanding the nature of the biota of early Earth. Molecular, genomics and phylogenetics data strengthen Woese's definition of Archaea as a third domain of life in addition to Bacteria and Eukarya. Phylogenomics analyses of the components of different molecular systems are highlighting a core of mainly vertically inherited genes in Archaea. This allows recovering a globally well-resolved picture of archaeal evolution, as opposed to what is observed for Bacteria and Eukarya. This may be due to the fact that no rapid divergence occurred at the emergence of present-day archaeal lineages. This phylogeny supports a hyperthermophilic and non-methanogenic ancestor to present-day archaeal lineages, and a profound divergence between two major phyla, the Crenarchaeota and the Euryarchaeota, that may not have an equivalent in the other two domains of life. Nanoarchaea may not represent a third and ancestral archaeal phylum, but a fast-evolving euryarchaeal lineage. Methanogenesis seems to have appeared only once and early in the evolution of Euryarchaeota. Filling up this picture of archaeal evolution by adding presently uncultivated species, and placing it back in geological time remain two essential goals for the future.
Black Bloggers and the Blogosphere

This paper explores the role of black bloggers in the blogosphere. Among the top political blogs, blogging has primarily been undertaken by white men, coined by Chris Nolan as the "Big Boys Club. " This research assesses how bloggers of color use their blogs for purposes related to politics, and it investigates whether the blogosphere facilitates political participation among black bloggers. The data for this paper are based on in-depth interviews with 20 black bloggers conducted in November 2005. Primarily exploratory, this paper examines the issues and topics discussed by bloggers of color, and whether and how bloggers are using their blogs to engage in political participation. In addition this research attempts to assess whether black bloggers face discrimination in the blogosphere. Findings from this research suggest that black bloggers do in fact use their blogs to encourage their readers to engage in various forms of political participation. Finally, the data also show that bloggers reported that they do not feel discriminated against or excluded by other bloggers.
Antibody Response to Cutaneous Leishmaniasis in Sudan

The role of antibody levels in protective immunity against cutaneous leishmaniasis (CL) is largely unknown. The aim of this study is to investigate the role of antibody response against CL among Sudanese population. Fifty six clinically diagnosed CL subjects were enrolled in this study. Forty eight of them had healed scar and eight have active lesions. The leishmanin skin test (LST) was 54.7% positive. The frequency of human IL4RP2 alleles was investigated in this study. The results showed 83.9% (183 bp) and 16.1% (253 bp) and the heterozygosity was 39%. The mean antibody levels using direct agglutination test (DAT) has found to be higher against Leishmania major (L. major) antigen than Leishmania donovani (L. donovani) antigen and the difference was found to be significant (P = 0.01 <0.05). The anti L. major IgG was quantified in this study using enzyme linked immunosorbent assay (ELISA). The mean of antibody levels measured by ELISA and DAT was significantly higher in study participants with scars more than those with skin lesions. Overall this outcome would be supportive to indicate a possible role of antibody-mediated protection in CL and would signify the importance of identification of antigens that may elicit protective antibodies.