RESUMEN
Neocortical vasoactive intestinal polypeptide-expressing (VIP+) interneurons display highly diverse morpho-electrophysiological and molecular properties. To begin to understand the function of VIP+ interneurons in cortical circuits, they must be clearly and comprehensively classified into distinct subpopulations based on specific molecular markers. Here, we utilized patch-clamp RT-PCR (Patch-PCR) to simultaneously obtain the morpho-electric properties and mRNA profiles of 155 VIP+ interneurons in layers 2 and 3 (L2/3) of the mouse somatosensory cortex. Using an unsupervised clustering method, we identified 3 electrophysiological types (E-types) and 2 morphological types (M-types) of VIP+ interneurons. Joint clustering based on the combined electrophysiological and morphological features resulted in 3 morpho-electric types (ME-types). More importantly, we found these 3 ME-types expressed distinct marker genes: ~94% of Sncg+ cells were ME-type 1, 100% of Mybpc1+ cells were ME-type 2, and ~78% of Parm1+ were ME-type 3. By clarifying the properties of subpopulations of cortical L2/3 VIP+ interneurons, this study establishes a basis for future investigations aiming to elucidate their physiological roles.
Asunto(s)
Corteza Somatosensorial , Péptido Intestinal Vasoactivo , Animales , Ratones , Fenómenos Electrofisiológicos , Interneuronas/fisiología , Corteza Somatosensorial/fisiología , Péptido Intestinal Vasoactivo/metabolismo , Proteínas de Neoplasias/metabolismo , gamma-Sinucleína/metabolismo , Proteína de Unión a Andrógenos/metabolismoRESUMEN
ATP-binding cassette transporter A1 (ABCA1) is a membrane-associated protein which has attracted considerable attention as a candidate gene for Alzheimer's disease (AD) based on its function as a key factor in lipid metabolism by mediating cellular cholesterol efflux, the rate-limiting step in the production of nascent high-density lipoprotein (HDL) particles. The relationship between ABCA1 common variations (R219 K rs2230806, I883 M rs4149313 and R1587 K rs2230808) and AD has been reported in various ethnic groups; however, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 13 studies involving a total of 12,248 subjects to evaluate the effect of ABCA1 on genetic susceptibility for AD. Overall, the summary OR of AD was 1.01 (95 % CI: 0.93-1.10; P = 0.77), 1.10 (95 % CI: 0.96-1.26; P = 0.16), and 1.08 (95 % CI: 0.96-1.23; P = 0.21) for R219 K, I883 M and R1587 K polymorphism, respectively. No significant results were observed in dominant and recessive when compared with wild genotype for these polymorphisms. In the stratified analyses by ethnicity and sample size, no evidence of any gene-disease association was obtained. In conclusion, the present meta-analysis does not support the notion that common SNPs on ABCA1 is a major genetic risk factor for AD.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Enfermedad de Alzheimer/genética , Polimorfismo de Nucleótido Simple , Transportador 1 de Casete de Unión a ATP , Sustitución de Aminoácidos , Estudios de Casos y Controles , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Factores de RiesgoRESUMEN
The incidence of welldifferentiated thyroid cancer (WDTC) is rapidly increasing. Poor survival follows distant metastasis (DM) and recurrence. In the present study, we aimed to analyze the expression alterations in different stages of WDTC and the regulatory mechanism of DM and the recurrence of DM. A male patient diagnosed with follicular thyroid cancer and distant metastasis in the eleventh thoracic vertebrae received total thyroidectomy and the removal of a metastatic lesion. A local relapse was found in the vertebrae after fourtime iodine131 treatment. We performed mRNA and microRNA microarray on the paracancerous, cancerous, metastatic and metastatic recurrent tissue. In combination with the data of The Cancer Genome Atlas (TCGA), we used bioinformatics approaches to analyze the common alterations and microRNAmRNA interactions among the processes of tumorigenesis and metastasis. Metastatic lesions and recurrent lesions were used to investigate the molecular mechanism of tumor evolution and recurrence in this case. A total of four mRNAs and two microRNAs were newly found to be related to patient survival in WDTC. The microRNAmRNA interactions were predicted for the overlapped mRNAs and microRNAs. Lineage deregulation of genes, such as CXC motif chemokine receptor 4 (CXCR4) and thyroglobulin (TG) were found from the tumorigenic stage to the metastatic stage. The ribosome pathway was highly enriched in the bone metastasis compared with the cancerous tissue. The downstreaming effects of p53 were impaired in the recurrent lesion due to deregulation of several functional genes. The integrated analysis with TCGA data indicated several prognostic markers and regulatory networks for potential treatment. Our results also provided possible molecular mechanisms in which the ribosome and p53 pathways may respectively contribute to bone metastasis and local recurrence of metastasis.
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Adenocarcinoma Folicular/genética , MicroARNs/genética , ARN Mensajero/genética , Neoplasias de la Tiroides/genética , Adenocarcinoma Folicular/patología , Adulto , Diferenciación Celular , Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Masculino , Metástasis de la Neoplasia , Estadificación de Neoplasias , Receptores CXCR4/genética , Neoplasias de la Tiroides/patología , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.
RESUMEN
OBJECTIVE: To estimate the effects of the treatment of 360 degrees fixation of lumbar spine. METHODS: Twenty-five cases were operated to 360 degrees fixation of lumbar spine from May 2002 to May 2005. There were 11 male and 14 female, the age ranging from 45 to 67 years, mean 56, including 16 cases of spondylolysis, 7 cases of lumbar spinal instability and 2 cases of degenerative disc undergone with anterior laparoscopic lumbar interbody fusion with syncage and autograft and posterior decompression with facet fixation. The chief complains were low back pain and radiating to lag. Fourteen cases were fused at L(4), 5 and 11 cases at L(5)-S(1). The Oswestry Disability Index (ODI) were recorded to evaluate the function at pro-operation, the second week, the third, sixth and twelfth month post-operation. The X-ray was taken to observe the fusion and the sinking cage. RESULTS: The time intro-operation was from 110 to 180 minutes, mean 120 minutes. There was one complication in 1 case by the main vein injury. All of the 25 cases were followed-up post-operation from 12 to 35 months, mean 22.3 months. The ODI was found prominent difference compared with pro-operation in 2 weeks, 3, 6 and 12 months post-operation (P < 0.05). Twenty-five cases were fused in the third month. Two cases sank 1 mm in the third month images but solid fusion. No cage displacement was found. No retrograde ejaculation happened. CONCLUSIONS: 360 degrees fixation of lumbar spine adapts to deal with lumbar instability, degenerative disc disease and I, II degree spondylolysis. It shows less bleeding and injury, but during exposure and traction the main vessels should be very careful.
Asunto(s)
Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Anciano , Descompresión Quirúrgica , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía , Masculino , Persona de Mediana EdadRESUMEN
Osteogenic growth peptide (OGP) has been synthesized through Fmoc solid phase synthesis procedure. The purity of synthetic OGP (sOGP) is over 98.6% identified by HPLC, the amino acid sequence and electro-spray mass spectroscopy are consistent with theoretical values. The synergetic effect of sOGP with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the hematopoiesis was investigated in normal mice. To assess the synergy of sOGP with rhG-CSF, two schemes were designed. In one scheme rhG-CSF was used at the last 8 days of a 13-day treatment with sOGP, while in the other one both cytokines were given concurrently for 10 days [sOGP, 0.5 nmol/day (mouse); rhG-CSF, 2 microg/day (mouse)]. Both schemes showed that sOGP remarkably synergized with rhG-CSF on increment of white blood cell number and lymphocyte number in peripheral blood without any change of red blood cell and platelet counts. Quantitative differential analysis of bone marrow and histological examination of the spleen and sternum showed that sOGP plus rhG-CSF did not cause abnormal hyperplasia, so sOGP is a very hopeful new drug to improve the effectiveness of clinical used rhG-CSF.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Sustancias de Crecimiento/farmacología , Péptidos y Proteínas de Señalización Intercelular/farmacología , Animales , Recuento de Células Sanguíneas , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Sinergismo Farmacológico , Sustancias de Crecimiento/síntesis química , Hematopoyesis/efectos de los fármacos , Histonas , Péptidos y Proteínas de Señalización Intercelular/síntesis química , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes , Bazo/citología , Bazo/efectos de los fármacosRESUMEN
PURPOSE: Studies investigating the association between PTPN22 gene C1858T polymorphism and type 1 diabetes (T1D) susceptibility among Caucasian population have reported conflicting results. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the PTPN22 C1858T polymorphism and T1D. METHODS: Databases including PubMed, Web of Science, and EMBASE were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. RESULTS: In total, 33 population-based studies with 22, 485 cases and 35, 292 controls, 9 family-based studies involving 7276 families were included. Under the random-effects model, the per-allele overall OR of the C1858T polymorphism for T1D was 1.89 (95% CI: 1.76-2.02, P<10(-5)) by pooling all available case-control studies. In addition, we found significant evidence for overtransmission of the risk T allele in family-based studies (overall OR (TDT)=1.58, 95% CI: 1.43-1.74; P<10(-5)). The summary OR from case-control and family-based association studies was 1.81 (95% CI: 1.70-1.93, P<10(-5)). CONCLUSIONS: In conclusion, this meta-analysis suggests that C1858T polymorphism in PTPN22 is associated with elevated T1D risk among Caucasian population.