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991.
Feedforward and feedback connections and their relation to the cytox modules of V2 in Cebus monkeys 下载免费PDF全文
Sheila Nascimento‐Silva Carmen Pinõn Juliana G.M. Soares Ricardo Gattass 《The Journal of comparative neurology》2014,522(13):3091-3105
To study the circuitry related to the ventral stream of visual information processing and its relation to the cytochrome oxidase (CytOx) modules in visual area V2, we injected anterograde and retrograde cholera toxin subunit B (CTb) tracer into nine sites in area V4 in five Cebus apella monkeys. The injection site locations ranged from 2° to 10° eccentricity in the lower visual field representation of V4. Alternate cortical sections, cut tangentially to the pial surface or in the coronal plane, were stained for CTb immunocytochemistry or for CytOx histochemistry or for Nissl. Our results indicate that the V4‐projecting cells and terminal‐like labeling were located in interstripes and thin CytOx‐rich stripes and avoided the CytOx‐rich thick stripes in V2. The feedforward projecting cell bodies in V2 were primarily located in the supragranular layers and sparsely located in the infragranular layers, whereas the feedback projections (i.e., the terminal‐like labels) were located in the supra‐ and infragranular layers. V4 injections of CTb resulted in labeling of the thin stripes and interstripes of V2 and provided an efficient method of distinguishing the V2 modules that were related to the ventral stream from the CytOx‐rich thick stripes, related to the dorsal stream. In V2, there was a significant heterogeneity in the distribution of projections: feedforward projections were located in CytOx‐rich thin stripes and in the CytOx‐poor interstripes, whereas the feedback projections were more abundant in the thin stripes than in the interstripes. J. Comp. Neurol. 522:3091–3105, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
992.
de Oliveira AC Andreotti S Farias Tda S Torres-Leal FL de Proença AR Campaña AB de Souza AH Sertié RA Carpinelli AR Cipolla-Neto J Lima FB 《Endocrinology》2012,153(5):2178-2188
Diabetes mellitus is a product of low insulin sensibility and pancreatic β-cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin can improve insulin resistance and other metabolic disorders in these animals. At the fourth week of age, diabetic animals started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking water at night. Animals were then killing, and the sc, epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Blood samples were collected for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by constant glucose disappearance rate and homeostasis model of assessment-insulin resistance. However, melatonin treatment was unable to recover body weight deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin, whereas neither plasma insulin level nor insulin secretion capacity was improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development, leaving genital structures smaller than those of nontreated diabetic animals. Melatonin treatment improved the responsiveness of adipocytes to insulin in diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose oxidation, and incorporation of glucose into lipids (EP and RP), an effect that seems partially related to an increased expression of insulin receptor substrate 1, acetyl-coenzyme A carboxylase and fatty acid synthase. In conclusion, melatonin treatment was capable of ameliorating the metabolic abnormalities in this particular diabetes model, including insulin resistance and promoting a better long-term glycemic control. 相似文献
993.
P Labarga P Barreiro A da Silva JM Guardiola R Rubio K Aguirrebengoa P Miralles J Portu MJ Téllez L Morano A Castro JA Pineda A Terrón J Hernández-Quero A Mariño MJ Ríos S Echeverría V Asensi E Vispo V Soriano;on behalf of PERICO Study Group 《The Journal of infectious diseases》2012,206(6):961-968
Background.?Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. Methods.?HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180?μg/d) plus either RBV standard dosing (1000 or 1200?mg/d if <75 or ≥75?kg, respectively) or RBV induction (2000?mg/d) along with subcutaneous erythropoietin β (450?IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. Results.?A total of 357 patients received ≥1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14?μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3?mg/dL; P?.005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P?=?.004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P?=?.007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P?=?.03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P?.001) as predictors of SVR. Conclusions.?A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV. 相似文献
994.
da Silva Xavier G Mondragon A Sun G Chen L McGinty JA French PM Rutter GA 《Diabetologia》2012,55(10):2667-2676
Aims/hypothesis
Individuals carrying type 2 diabetes risk alleles in TCF7L2 display decreased beta cell levels of T cell factor 7 like-2 (TCF7L2) immunoreactivity, and impaired insulin secretion and beta cell sensitivity to glucagon-like peptide 1 (GLP-1). Here, we sought to determine whether selective deletion of Tcf7l2 in mouse pancreas impairs insulin release and glucose homeostasis. 相似文献995.
Sousa M Simões HG Castro CC Otaduy MC Negrão CE Pereira RM Madsen K Silva ME 《Metabolism: clinical and experimental》2012,61(8):1189-1196
The objective was to determine the effects of carbohydrate (CHO) supplementation on exercise-induced hormone responses and post-training intramyocellular lipid stores (IMCL). Twenty-four elite male athletes (28.0 ± 1.2 years) were randomized to receive CHO (maltodextrin solution) or zero energy placebo solution (control group). The high-intensity running protocol consisted of 10 × 800 m at 100% of the best 3000-m speed (Vm3 km) and 2 × 1000 m maximal bouts in the morning and a submaximal 10-km continuous easy running in the afternoon of day 9. IMCL concentrations were assessed by 1H-MRS before (?day 9) and after training (day 9) in soleus (SO) and tibialis anterior (TA) muscles. Blood hormones were also measured before, during, and post-exercise. The percent change (Δ%) in TA-IMCL was higher in the CHO group (47.9 ± 24.5 IMCL/Cr) than in the control group (?1.7 ± 13.1, respectively) (P = .04). Insulin concentrations were higher in the CHO group post-intermittent running compared to control (P = .02). Circulating levels of free fatty acids and GH were lower in the CHO group (P > .01). The decline in performance in the 2nd 1000-m bout was also attenuated in this group compared to control (P < .001 and P = .0035, respectively). The hormonal milieu (higher insulin and lower GH levels) in the CHO group, together with unchanged free fatty acid levels, probably contributed to the increased IMCL stores. This greater energy storage capacity may have improved post-exercise recovery and thus prevented performance deterioration. 相似文献
996.
Leite RD Kraemer-Aguiar LG Boa BC Cyrino FZ Nivoit P Bouskela E 《Microvascular research》2012,84(1):94-98
The aims of our study were to investigate effects of postnatal overnutrition, obtained by restricting the number of pups per litter, on microcirculatory reactivity, fat depots, its total percentage and lipid profile. Microvascular reactivity was evaluated in the cremaster muscle of 24 hamsters divided into four groups, with 6 animals in each one: normal (NL) and restricted (RL) litter groups, both at 6th and 21st weeks of age. The NL group had 8-9 pups and the RL 3 pups per litter and to avoid the litter effect, only one animal was used per litter. The results have shown that the RL group had higher velocity of weight, body mass and fat gain compared to the NL one at weeks 6 and 21. Significant differences were also observed on urogenital fat depot, total cholesterol and low density lipoprotein between groups. At the lowest concentration of Ach, the RL group showed smaller arteriolar dilatation at the 21st than at the 6th week [5(3-13) vs 19(8-40)%, p<0.01] while the NL one did not show any difference within the group. The highest concentration of Ach at the 21th week pointed to endothelial-dependent microvascular dysfunction in RL compared to NL [3(8-26) vs. 13(8-26)%, p<0.05]. Endothelial-independent microvascular reactivity was similar between groups. Our data suggest that postnatal overnutrition is associated to muscle endothelial-dependent microvascular dysfunction, greater body mass and total percentage of fat and impaired the lipid profile. In conclusion, the imprinting promoted by this experimental model of obesity was able to influence microvascular reactivity later in life. 相似文献
997.
de Alwis R Smith SA Olivarez NP Messer WB Huynh JP Wahala WM White LJ Diamond MS Baric RS Crowe JE de Silva AM 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(19):7439-7444
Dengue is a mosquito-borne flavivirus that is spreading at an unprecedented rate and has developed into a major health and economic burden in over 50 countries. Even though infected individuals develop potent and long-lasting serotype-specific neutralizing antibodies (Abs), the epitopes engaged by human neutralizing Abs have not been identified. Here, we demonstrate that the dengue virus (DENV)-specific serum Ab response in humans consists of a large fraction of cross-reactive, poorly neutralizing Abs and a small fraction of serotype-specific, potently inhibitory Abs. Although many mouse-generated, strongly neutralizing monoclonal antibodies (mAbs) recognize epitopes that are present on recombinant DENV envelope (E) proteins, unexpectedly, the majority of neutralizing Abs in human immune sera bound to intact virions but not to the ectodomain of purified soluble E proteins. These conclusions with polyclonal Abs were confirmed with newly generated human mAbs derived from DENV-immune individuals. Two of three strongly neutralizing human mAbs bound to E protein epitopes that were preserved on the virion but not on recombinant E (rE) protein. We propose that humans produce Abs that neutralize DENV infection by binding a complex, quaternary structure epitope that is expressed only when E proteins are assembled on a virus particle. Mapping studies indicate that this epitope has a footprint that spans adjacent E protein dimers and includes residues at the hinge between domains I and II of E protein. These results have significant implications for the DENV Ab and vaccine field. 相似文献
998.
Adamo A Woglar A Silva N Penkner A Jantsch V La Volpe A 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(9):3440-3445
Introduction of multiple copies of a germ-line-expressed gene elicits silencing of the corresponding endogenous gene during Caenorhabditis elegans oogenesis; this process is referred to as germ-line cosuppression. Transformed plasmids assemble into extrachromosomal arrays resembling extra minichromosomes with repetitive structures. Loss of the transgene extrachromosomal array leads to reversion of the silencing phenomenon. Cosuppression and RNAi depend upon some of the same genes. In the C. elegans germ line, about half the cells undergo a physiological programmed cell death that shares most genetic requirements with somatic apoptosis. In addition, apoptosis is stimulated by DNA damage and synaptic failure mediated through different apoptotic checkpoints. We found that both germ-line cosuppression and RNAi of germ-line-expressed genes enhance apoptosis during C. elegans oogenesis. In contrast, apoptosis is not enhanced by extrachromosomal arrays carrying genes not driven by germ-line-specific promoters that thus do not elicit transgene-mediated cosuppression/silencing. Similarly, introduction of doubled-stranded RNA that shares no homology with endogenous genes has no effect on apoptosis. "Silencing-induced apoptosis" is dependent upon sir-2.1 and cep-1 (the worm p53 ortholog), and is accompanied by a rise in RAD-51 foci, a marker for ongoing DNA repair, indicating induction of DNA double-strand breaks. This finding suggests that the DNA damage-response pathway is involved. RNAi and cosuppression have been postulated as defense mechanisms against genomic intruders. We speculate that the mechanism here described may trigger the elimination of germ cells that have undergone viral infection or transposon activation. 相似文献
999.
AT van der Goot W Zhu RP Vázquez-Manrique RI Seinstra K Dettmer H Michels F Farina J Krijnen R Melki RC Buijsman M Ruiz Silva KL Thijssen IP Kema C Neri PJ Oefner EA Nollen 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(37):14912-14917
Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer's diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of tdo-2 also suppresses toxicity of other heterologous aggregation-prone proteins, including amyloid-β and polyglutamine proteins, and endogenous metastable proteins that are sensors of normal protein homeostasis. This finding suggests that tdo-2 functions as a general regulator of protein homeostasis. Analysis of metabolite levels in C. elegans strains with mutations in enzymes that act downstream of tdo-2 indicates that this suppression of toxicity is independent of downstream metabolites in the kynurenine pathway. Depletion of tdo-2 increases tryptophan levels, and feeding worms with extra l-tryptophan also suppresses toxicity, suggesting that tdo-2 regulates proteotoxicity through tryptophan. Depletion of tdo-2 extends lifespan in these worms. Together, these results implicate tdo-2 as a metabolic switch of age-related protein homeostasis and lifespan. With TDO and Indoleamine 2,3-dioxygenase as evolutionarily conserved human orthologs of TDO-2, intervening with tryptophan metabolism may offer avenues to reducing proteotoxicity in aging and age-related diseases. 相似文献
1000.
Lima NA Vasconcelos CC Filgueira PH Kretzmann M Sindeaux TA Feitosa Neto B Silva Junior GB Daher EF 《Revista do Instituto de Medicina Tropical de S?o Paulo》2012,54(1):57-60
Tuberculosis (TB) is a current public health problem, remaining the most common worldwide cause of mortality from infectious disease. Recent studies indicate that genitourinary TB is the third most common form of extra-pulmonary disease. The diagnosis of renal TB can be hypothesized in a non-specific bacterial cystitis associated with a therapeutic failure or a urinalysis with a persistent leukocyturia in the absence of bacteriuria. We report on the case of a 33-year-old man who presented on admission end stage renal disease (ESRD) secondary to renal TB and a past history of pulmonary TB with important radiologic findings. The diagnosis was based on clinical findings despite all cultures being negative. Empiric treatment with tuberculostatic drugs was started and the patient became stable. He was discharged with no symptom, but without renal function recovery. He is on maintenance hemodialysis three times a week. TB is an important cause of kidney disease and can lead to irreversible renal function loss. 相似文献