Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due to a marked reduction in fat cell mass without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is accompanied by increased basal metabolic rate and total energy expenditure, without marked alteration of uncoupling protein mRNA expression. In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies. Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle, whereas adipose tissue is unaffected. Our results identify PTP-1B as a major regulator of energy balance, insulin sensitivity, and body fat stores in vivo.     

Speech graphs provide a quantitative measure of thought disorder in psychosis

Background

Psychosis has various causes, including mania and schizophrenia. Since the differential diagnosis of psychosis is exclusively based on subjective assessments of oral interviews with patients, an objective quantification of the speech disturbances that characterize mania and schizophrenia is in order. In principle, such quantification could be achieved by the analysis of speech graphs. A graph represents a network with nodes connected by edges; in speech graphs, nodes correspond to words and edges correspond to semantic and grammatical relationships.

Methodology/Principal Findings

To quantify speech differences related to psychosis, interviews with schizophrenics, manics and normal subjects were recorded and represented as graphs. Manics scored significantly higher than schizophrenics in ten graph measures. Psychopathological symptoms such as logorrhea, poor speech, and flight of thoughts were grasped by the analysis even when verbosity differences were discounted. Binary classifiers based on speech graph measures sorted schizophrenics from manics with up to 93.8% of sensitivity and 93.7% of specificity. In contrast, sorting based on the scores of two standard psychiatric scales (BPRS and PANSS) reached only 62.5% of sensitivity and specificity.

Conclusions/Significance

The results demonstrate that alterations of the thought process manifested in the speech of psychotic patients can be objectively measured using graph-theoretical tools, developed to capture specific features of the normal and dysfunctional flow of thought, such as divergence and recurrence. The quantitative analysis of speech graphs is not redundant with standard psychometric scales but rather complementary, as it yields a very accurate sorting of schizophrenics and manics. Overall, the results point to automated psychiatric diagnosis based not on what is said, but on how it is said.     

Apert p.Ser252Trp mutation in FGFR2 alters osteogenic potential and gene expression of cranial periosteal cells

Apert syndrome (AS), a severe form of craniosynostosis, is caused by dominant gain-of-function mutations in FGFR2. Because the periosteum contribution to AS cranial pathophysiology is unknown, we tested the osteogenic potential of AS periosteal cells (p.Ser252Trp mutation) and observed that these cells are more committed toward the osteoblast lineage. To delineate the gene expression profile involved in this abnormal behavior, we performed a global gene expression analysis of coronal suture periosteal cells from seven AS patients (p.Ser252Trp), and matched controls. We identified 263 genes with significantly altered expression in AS samples (118 upregulated, 145 downregulated; SNR >or= |0.4|, P 相似文献   

Gold(I) complexes with thiosemicarbazones: cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Complexes [Au(H2Ac4DH)Cl]?MeOH (1) [Au(H₂2Ac4Me)Cl]Cl (2) [Au(H₂2Ac4Ph)Cl]Cl?2H₂O (3) and [Au(H₂2Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action.     

Synergic effects of ultrasound and laser therapies on mesentery for management of obesity and diabetes in rats

Nowadays, the mesentery as a new organ was discovered. Mesenteric events may play an important role in the pathophysiology of several diseases. The aim of our study was investigate the synergic effects of ultrasound (US) and laser therapies on mesentery in obese-hyperglycemic rats. The 25 male Wistar rats were randomized into five groups. Obese nondiabetic (OND) group: obese rats without diabetes and no treatment conditions; SHAM group: obese-hyperglycemic rats treated with placebo; US group: obese-hyperglycemic rats treated with US; LASER group: obese-hyperglycemic rats treated with laser and; US+LASER group: obese-hyperglycemic rats treated with US plus laser. An animal model of type 2 diabetes based on a hyperlipidemic diet combined with a low dose of streptozotocin was used in this study. Body mass and biochemical measurements were performed. GOT and GPT level showed a significant reduction in the treated groups than SHAM. The total cholesterol, triglycerides and very low-density lipoprotein (VLDL) levels showed significantly lower values for the US+LASER group. There was also reduced risk of cardiovascular diseases evidenced by Castelli index in the treated groups than SHAM. This study showed that the US and laser treatment on mesentery resulted to an improvement in biochemical measurements of the obese-hyperglycemic rats, especially the total cholesterol, triglycerides and VLDL levels.     

The spatial distribution of chloroplast DNA and allozyme polymorphisms within A population of Silene alba (Caryophyllaceae)

Genetic structure within a population of Silene alba was studied using a chloroplast DNA (cpDNA) and six allozyme polymorphisms. A 20 × 65 m area was sampled by constructing a 5 × 5 m grid and determining the genotype of the plant nearest to each grid node. Analysis of the spatial distribution of genotypes by Moran's I and join-counts showed a significant degree of association of like cpDNA haplotypes (I = 0.52, S.N.D. = 2.55) but a random or slightly repulsed distribution of allozyme genotypes. A second sample was taken by collecting all individuals from within a 1-m wide transect established along the perimeter of the grid. Genotype and allele frequencies were calculated by grouping individuals from arbitrary 3-m intervals along the transect, and analyzed by Wright's F statistics. The F_st value calculated for cpDNA (0.875) differed markedly from that based on all allozymes (0.027). Taken together, the results suggest that in this population gene flow in the maternally inherited cpDNA is limited by restricted seed dispersal, whereas gene flow in the nuclear DNA based allozymes is more pervasive owing to the added effects of pollen dispersal. The utility of cpDNA polymorphism for the study of fine-scale gene flow is discussed.     

The effects of transcranial laser photobiomodulation and neuromuscular electrical stimulation in the treatment of post-stroke dysfunctions

Post-stroke sequelae includes loss functions, such as cognitive and sensory-motor which lead to emotional and social problems, reducing quality of life and well-being. The main aim of our study was to investigate the effects of transcranial laser photobiomodulation together with neuromuscular electrical stimulation (NMES) in post-stroke patients. We performed a clinical trial and an ex vivo study. For the clinical trial, hemiplegic patients were separated into two groups: Treated Group (TG): Hemiplegics treated with transcranial laser (on) associated with NMES (on) and; Placebo Group (PG): Hemiplegics treated with placebo transcranial laser (off) associated with NMES (on). The cluster prototype includes 12 diode laser beams (4 × 660 nm, 4 × 808 nm and 4 × 980 nm) with average power of 720 mW per cluster applied during one minute, leading to 43.2 J energy per cluster. Fifteen regions for all head were irradiated by cluster, leading to 648 J energy per session. The parameters of NMES of the paretic limbs to generate extension wrist and ankle dorsiflexion were symmetrical biphasic rectangular waveforms, 50 Hz frequency, 250 μs pulse duration, and adjustable intensity to maintain the maximum range of motion (amplitude between 0 and 150 mA). Our clinical trial showed improvement of cognitive function, pain relief, greater manual dexterity, enhancement of physical and social–emotional health which lead to better quality of life and well-being. There was also increased temperature in the treated regions with laser and NMES. For the ex vivo study, the distribution of infrared and red radiation after penetration through the cranium and hemihead of cadavers were showed. Therefore, transcranial laser photobiomodulation associated with NMES can be an important therapeutic resource for rehabilitation after stroke.     

An assessment of antituberculosis therapy in two animal models

The protective effects of ciprofloxacin and rufloxacin were compared to those of rifampicin againstMycobacterium tuberculosis infections in mice and in guinea pigs. Rifampicin was very protective in both models. In tubercular infections produced in mice, ciprofloxacin (30 mg/kg) showed slight protection but none was observed in guinea pigs. Rufloxacin, was weakly active in guinea pigs but inactive in mice.