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排序方式: 共有10000条查询结果,搜索用时 31 毫秒
961.
Matthew B. Harms Janet Cady Craig Zaidman Paul Cooper Taha Bali Peggy Allred Carlos Cruchaga Michael Baughn Ryan T. Libby Alan Pestronk Alison Goate John Ravits Robert H. Baloh 《Neurobiology of aging》2013
Hexanucleotide repeat expansions in C9ORF72 are a common cause of familial and apparently sporadic amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The mechanism by which expansions cause neurodegeneration is unknown, but current evidence supports both loss-of-function and gain-of-function mechanisms. We used pooled next-generation sequencing of the C9ORF72 gene in 389 ALS patients to look for traditional loss-of-function mutations. Although rare variants were identified, none were likely to be pathogenic, suggesting that mutations other than the repeat expansion are not a common cause of ALS, and providing supportive evidence for a gain-of-function mechanism. We also show by repeat-primed PCR genotyping that the C9ORF72 expansion frequency varies by geographical region within the United States, with an unexpectedly high frequency in the Mid-West. Finally we also show evidence of somatic instability of the expansion size by Southern blot, with the largest expansions occurring in brain tissue. 相似文献
962.
Aura Muntasell Carlos Vilches Ana Angulo Miguel López‐Botet 《European journal of immunology》2013,43(5):1133-1141
As discussed in this review, human cytomegalovirus (HCMV) infection in healthy individuals is associated with a variable and persistent increase of NK cells expressing the CD94/NKG2C activating receptor. The expansion of NKG2C+ NK cells reported in other infectious diseases is systematically associated with HCMV co‐infection. The functionally mature NKG2Cbright NK‐cell subset expanding in HCMV+ individuals displays inhibitory Ig‐like receptors (KIR and LILRB1) specific for self HLA class I, and low levels of NKp46 and NKp30 activating receptors. Such reconfiguration of the NK‐cell compartment appears particularly marked in immunocompromised patients and in children with symptomatic congenital infection, thus suggesting that its magnitude may be inversely related with the efficiency of the T‐cell‐mediated response. This effect of HCMV infection is reminiscent of the pattern of response of murine Ly49H+ NK cells against murine CMV (MCMV), and it has been hypothesized that a cognate interaction of the CD94/NKG2C receptor with HCMV‐infected cells may drive the expansion of the corresponding NK‐cell subset. Yet, the precise role of NKG2C+ cells in the control of HCMV infection, the molecular mechanisms underlying the NK‐cell compartment redistribution, as well as its putative influence in the response to other pathogens and tumors remain open issues. 相似文献
963.
Jennifer Van Grol Luis Muniz-Feliciano Jose-Andres C. Portillo Vera L. Bonilha Carlos S. Subauste 《Infection and immunity》2013,81(6):2002-2011
Toxoplasma gondii infects both hematopoietic and nonhematopoietic cells and can cause cerebral and ocular toxoplasmosis, as a result of either congenital or postnatally acquired infections. Host protection likely acts at both cellular levels to control the parasite. CD40 is a key factor for protection against cerebral and ocular toxoplasmosis. We determined if CD40 induces anti-T. gondii activity at the level of nonhematopoietic cells. Engagement of CD40 on various endothelial cells including human microvascular brain endothelial cells, human umbilical vein endothelial cells, and a mouse endothelial cell line as well as human and mouse retinal pigment epithelial cells resulted in killing of T. gondii. CD40 stimulation increased expression of the autophagy proteins Beclin 1 and LC3 II, enhanced autophagy flux, and led to recruitment of LC3 around the parasite. The late endosomal/lysosomal marker LAMP-1 accumulated around the parasite in CD40-stimulated cells. This was accompanied by killing of T. gondii dependent on lysosomal enzymes. Accumulation of LAMP-1 and killing of T. gondii were dependent on the autophagy proteins Beclin 1 and Atg7. Together, these studies revealed that CD40 induces toxoplasmacidal activity in various nonhematopoietic cells dependent on proteins of the autophagy machinery. 相似文献
964.
Carlos J. Blondel Juan C. Jiménez Lorenzo E. Leiva Sergio A. álvarez Bernardo I. Pinto Francisca Contreras David Pezoa Carlos A. Santiviago Inés Contreras 《Infection and immunity》2013,81(4):1207-1220
Salmonella enterica serotype Gallinarum is the causative agent of fowl typhoid, a disease characterized by high morbidity and mortality that causes major economic losses in poultry production. We have reported that S. Gallinarum harbors a type VI secretion system (T6SS) encoded in Salmonella pathogenicity island 19 (SPI-19) that is required for efficient colonization of chicks. In the present study, we aimed to characterize the SPI-19 T6SS functionality and to investigate the mechanisms behind the phenotypes previously observed in vivo. Expression analyses revealed that SPI-19 T6SS core components are expressed and produced under in vitro bacterial growth conditions. However, secretion of the structural/secreted components Hcp1, Hcp2, and VgrG to the culture medium could not be determined, suggesting that additional signals are required for T6SS-dependent secretion of these proteins. In vitro bacterial competition assays failed to demonstrate a role for SPI-19 T6SS in interbacterial killing. In contrast, cell culture experiments with murine and avian macrophages (RAW264.7 and HD11, respectively) revealed production of a green fluorescent protein-tagged version of VgrG soon after Salmonella uptake. Furthermore, infection of RAW264.7 and HD11 macrophages with deletion mutants of SPI-19 or strains with genes encoding specific T6SS core components (clpV and vgrG) revealed that SPI-19 T6SS contributes to S. Gallinarum survival within macrophages at 20 h postuptake. SPI-19 T6SS function was not linked to Salmonella-induced cytotoxicity or cell death of infected macrophages, as has been described for other T6SS. Our data indicate that SPI-19 T6SS corresponds to a novel tool used by Salmonella to survive within host cells. 相似文献
965.
Ahmad Almilaji Carlos Munoz Bernat Elvira Abul Fajol Tatsiana Pakladok Sabina Honisch Ekaterina Shumilina Florian Lang Michael Föller 《Pflügers Archiv : European journal of physiology》2013,465(11):1573-1582
Besides their role in cardiac repolarization, human ether-a-go-go-related gene potassium (hERG) channels are expressed in several tumor cells including rhabdomyosarcoma cells. The channels foster cell proliferation. Ubiquitously expressed AMP-dependent protein kinase (AMPK) is a serine-/threonine kinase, stimulating energy-generating and inhibiting energy-consuming processes thereby helping cells survive periods of energy depletion. AMPK has previously been shown to regulate Na+/K+ ATPase, Na+/Ca2+ exchangers, Ca2+ channels and K+ channels. The present study tested whether AMPK regulates hERG channel activity. Wild type AMPK (α1β1γ1), constitutively active γR70QAMPK (α1β1γ1(R70Q)), or catalytically inactive αK45RAMPK (α1(K45R)β1γ1) were expressed in Xenopus oocytes with hERG. Tail currents were determined as a measure of hERG channel activity by two-electrode-voltage clamp. hERG membrane abundance was quantified by chemiluminescence and visualized by immunocytochemistry and confocal microscopy. Moreover, hERG currents were measured in RD rhabdomyosarcoma cells after pharmacological modification of AMPK activity using the patch clamp technique. Coexpression of wild-type AMPK and of constitutively active γR70QAMPK significantly downregulated the tail currents in hERG-expressing Xenopus oocytes. Pharmacological activation of AMPK with AICAR or with phenformin inhibited hERG currents in Xenopus oocytes, an effect abrogated by AMPK inhibitor compound C. γR70QAMPK enhanced the Nedd4-2-dependent downregulation of hERG currents. Coexpression of constitutively active γR70QAMPK decreased membrane expression of hERG in Xenopus oocytes. Compound C significantly enhanced whereas AICAR tended to inhibit hERG currents in RD rhabdomyosarcoma cells. AMPK is a powerful regulator of hERG-mediated currents in both, Xenopus oocytes and RD rhabdomyosarcoma cells. AMPK-dependent regulation of hERG may be particularly relevant in cardiac hypertrophy and tumor growth. 相似文献
966.
Balasaheb Siraskar Dan Yang Huang Tatsiana Pakladok Gulab Siraskar Mentor Sopjani Ioana Alesutan Yulia Kucherenko Ahmad Almilaji Vasudharani Devanathan Ekaterina Shumilina Michael Föller Carlos Munoz Florian Lang 《Pflügers Archiv : European journal of physiology》2013,465(2):233-245
The 5′-adenosine monophosphate-activated serine/threonine protein kinase (AMPK) is stimulated by energy depletion, increase in cytosolic Ca2+ activity, oxidative stress, and nitric oxide. AMPK participates in the regulation of the epithelial Na+ channel ENaC and the voltage-gated K+ channel KCNE1/KCNQ1. It is partially effective by decreasing PIP2 formation through the PI3K pathway. The present study explored whether AMPK regulates the renal outer medullary K+ channel ROMK. To this end, cRNA encoding ROMK was injected into Xenopus oocytes with and without additional injection of constitutively active AMPKγR70Q (AMPKα1-HA+AMPKβ1-Flag+AMPKγ1R70Q), or of inactive AMPKαK45R (AMPKα1K45R+AMPKβ1-Flag+AMPKγ1-HA), and the current determined utilizing two-electrode voltage-clamp and single channel patch clamp. ROMK protein abundance was measured utilizing chemiluminescence in Xenopus oocytes and western blot in whole kidney tissue. Moreover, renal Na+ and K+ excretion were determined in AMPKα1-deficient mice (ampk ?/? ) and wild-type mice (ampk +/+ ) prior to and following an acute K+ load (111 mM KCl, 30 mM NaHCO3, 4.7 mM NaCl, and 2.25 g/dl BSA) at a rate of 500 μl/h. As a result, coexpression of AMPKγR70Q but not of AMPKαK45R significantly decreased the current in ROMK1-expressing Xenopus oocytes. Injection of phosphatidylinositol PI(4,5)P2 significantly increased the current in ROMK1-expressing Xenopus oocytes, an effect reversed in the presence of AMPKγR70Q. Under control conditions, no significant differences between ampk ?/? and ampk +/+ mice were observed in glomerular filtration rate (GFR), urinary flow rate, serum aldosterone, plasma Na+, and K+ concentrations as well as absolute and fractional Na+ and K+ excretion. Following an acute K+ load, GFR, urinary flow rate, serum aldosterone, plasma Na+, and K+ concentration were again similar in both genotypes, but renal absolute and fractional Na+ and K+ excretion were higher in ampk ?/? than in ampk +/+ mice. According to micropuncture following a K+ load, delivery of Na+ to the early distal tubule but not delivery of K+ to late proximal and early distal tubules was increased in ampk ?/? mice. The upregulation of renal ROMK1 protein expression by acute K+ load was more pronounced in ampk ?/? than in ampk +/+ mice. In conclusion, AMPK downregulates ROMK, an effect compromising the ability of the kidney to excrete K+ following an acute K+ load. 相似文献
967.
Camila Alexandrina Figueiredo PhD Maurício Lima Barreto Neuza Maria Alcantara-Neves Laura Cunha Rodrigues Philip John Cooper Alvaro A. Cruz Lain Carlos Pontes-de-Carvalho Denise C. Lemaire Ryan dos Santos Costa Leila D. Amorim Candelaria Vergara Nicholas Rafaels Li Gao Cassandra FosterMonica Campbell BS Rasika A. Mathias Kathleen C. Barnes 《The Journal of allergy and clinical immunology》2013
968.
Carmen Vidal Liliana Porras-Hurtado Raquel Cruz Joaquín Quiralte Victoria Cardona Carlos Colás Luisa F. Castillo Carmen Marcos Teresa Soto Raquel Lopez-Abad Dolores Hernández Maria Teresa Audicana Margarita Armisén Virginia Rodríguez Celsa Perez-Carral Esther Moreno Rosario Cabañes Mercè Corominas Antonio Parra Teófilo Lobera Dolores Quiñones Pedro Ojeda Ildefonso Luna María Torres Angel Carracedo 《The Journal of allergy and clinical immunology》2013
969.
Carlos Isaza Julieta Henao Leonardo Beltrán Liliana Porras Martha Gonzalez Raquel Cruz Angel Carracedo 《Colombia Médica》2013,44(1):19-25
Objective:
Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity.Methods:
A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, DβH and CYP2B6 genes. For the identification of alleles markers were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of cases and controls was analyzed with 61 AIMs.Results:
The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 years and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls in relation to schooling, marital status, social security family history of substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T ABCB1 gene (p= 0.001) were found.Conclusion:
The present results indicate that the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene, are both associated with addictive behavior to heroin or cocaine. 相似文献970.
Prevalence of poor self-rated health and associated risk factors among older adults in Cali,Colombia
José M Ocampo-Chaparro Helmer de J Zapata-Ossa ángela M Cubides-Munévar Carmen L Curcio Juan de D Villegas Carlos A Reyes-Ortiz 《Colombia Médica》2013,44(4):224-231