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排序方式: 共有897条查询结果,搜索用时 15 毫秒
31.
José M. Bravo-San Pedro Mireia Niso-Santano Rubén Gómez-Sánchez Elisa Pizarro-Estrella Ana Aiastui-Pujana Ana Gorostidi Vicente Climent Rakel López de Maturana Rosario Sanchez-Pernaute Adolfo López de Munain José M. Fuentes Rosa A. González-Polo 《Cellular and molecular life sciences : CMLS》2013,70(1):121-136
Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson’s disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells. 相似文献
32.
Lorena Beatriz Quiroga María Daniela Moreno Ariel Aníbal Cataldo Juan Héctor Aragón-Traverso María Victoria Pantano Juan Pablo Segundo Olivares 《Journal of Natural History》2015,49(27-28):1703-1716
The American bullfrog Lithobates catesbeianus has been introduced around the world, with invasive populations reported from almost all South American countries. A population of this species was introduced in the Calingasta department of San Juan province, which is an arid environment in western Argentina. This work provides information on the dietary composition of an invasive population of L. catesbeianus, and compares the degree of dietary overlap between adults and juveniles. Stomach contents of 169 bullfrogs (82 adults and 87 juveniles) were analysed. Adults consumed 40 prey taxa and Hymenoptera (Insecta) was the most numerous prey item (41.8%), followed by Araneae (13.6%) and Aeglidae (13.4%). Juveniles consumed 29 prey taxa and Hymenoptera constituted the highest percentage in prey number (77.2%). The trophic overlap niche index at the same level shows a value of 0.64 overlap in dietary community between adults and juveniles of this bullfrog. Aeglidae was volumetrically the most important trophic item (25.4%), followed by Anura (25.02%). Our results showed that cannibalism in bullfrogs is more common than the consumption of native anurans, coinciding with that reported in other populations of introduced bullfrogs. The high similarity in the diets of both size classes and the association between the size of the predator and prey suggest that the impact caused by bullfrogs throughout their ontogeny is high and probably has an impact on their prey. Freshwater crabs are the main items in the diet of Lithobates catesbeianus in other introduced populations and are usually the most conspicuous at our study site. The crabs in freshwater ecosystems are part of the lowest trophic level in the food chain. The major threats to the southern region’s freshwater crabs include deforestation, farming and exotic species. Lithobates catesbeianus has a generalist diet and high overlap between adults and juveniles. 相似文献
33.
Sandra Gómez-López Robin G. Lerner Claudia Petritsch 《Cellular and molecular life sciences : CMLS》2014,71(4):575-597
Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through controlled asymmetric divisions and is necessary to generate cellular diversity during development and to maintain adult tissue homeostasis. Disruption of this balance may result in premature depletion of the stem/progenitor cell pool, or abnormal growth. In many tissues, including the brain, dysregulated asymmetric divisions are associated with cancer. Whether there is a causal relationship between asymmetric cell division defects and cancer initiation is as yet not known. Here, we review the cellular and molecular mechanisms that regulate asymmetric cell divisions in the neural lineage and discuss the potential connections between this regulatory machinery and cancer. 相似文献
34.
Géza Tamás Szabó Bettina Tarr Krisztina Pálóczi Katalin Éder Eszter Lajkó Ágnes Kittel Sára Tóth Bence György Mária Pásztói Andrea Németh Xabier Osteikoetxea Éva Pállinger András Falus Katalin Szabó-Taylor Edit Irén Buzás 《Cellular and molecular life sciences : CMLS》2014,71(20):4055-4067
Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic, or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays and ELISA, and by testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic upregulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time. 相似文献
35.
From April to July 2008, we surveyed for breeding plovers at 32 sites in the semiarid highlands of Jalisco, Aguascalientes, Zacatecas, and San Luis Potosí, in the Central Mexican High Plateau. We documented evidence or presumption of breeding Snowy Plovers ( Charadrius alexandrinus ) at 3 sites, Killdeer ( C. vociferus ) at 15 sites, and Mountain Plovers ( C. montanus ) at 1 site. Our surveys showed that the region is important breeding ground for only the Killdeer. We documented an apparent breeding range extension of the Mountain Plover to slightly more than 200 km south of its previously known breeding range. 相似文献
36.
Purdue MP Johansson M Zelenika D Toro JR Scelo G Moore LE Prokhortchouk E Wu X Kiemeney LA Gaborieau V Jacobs KB Chow WH Zaridze D Matveev V Lubinski J Trubicka J Szeszenia-Dabrowska N Lissowska J Rudnai P Fabianova E Bucur A Bencko V Foretova L Janout V Boffetta P Colt JS Davis FG Schwartz KL Banks RE Selby PJ Harnden P Berg CD Hsing AW Grubb RL Boeing H Vineis P Clavel-Chapelon F Palli D Tumino R Krogh V Panico S Duell EJ Quirós JR Sanchez MJ Navarro C Ardanaz E Dorronsoro M Khaw KT Allen NE 《Nature genetics》2011,43(1):60-65
37.
Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease 总被引:1,自引:0,他引:1
Trynka G Hunt KA Bockett NA Romanos J Mistry V Szperl A Bakker SF Bardella MT Bhaw-Rosun L Castillejo G de la Concha EG de Almeida RC Dias KR van Diemen CC Dubois PC Duerr RH Edkins S Franke L Fransen K Gutierrez J Heap GA Hrdlickova B Hunt S Izurieta LP Izzo V Joosten LA Langford C Mazzilli MC Mein CA Midah V Mitrovic M Mora B Morelli M Nutland S Núñez C Onengut-Gumuscu S Pearce K Platteel M Polanco I Potter S Ribes-Koninckx C Ricaño-Ponce I Rich SS Rybak A Santiago JL Senapati S Sood A 《Nature genetics》2011,43(12):1193-1201
Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease. 相似文献
38.
Gutiérrez-López MD Gilsanz A Yáñez-Mó M Ovalle S Lafuente EM Domínguez C Monk PN González-Alvaro I Sánchez-Madrid F Cabañas C 《Cellular and molecular life sciences : CMLS》2011,68(19):3275-3292
ADAM17/TACE is a metalloproteinase responsible for the shedding of the proinflammatory cytokine TNF-α and many other cell
surface proteins involved in development, cell adhesion, migration, differentiation, and proliferation. Despite the important
biological function of ADAM17, the mechanisms of regulation of its metalloproteinase activity remain largely unknown. We report
here that the tetraspanin CD9 and ADAM17 partially co-localize on the surface of endothelial and monocytic cells. In situ
proximity ligation, co-immunoprecipitation, crosslinking, and pull-down experiments collectively demonstrate a direct association
between these molecules. Functional studies reveal that treatment with CD9-specific antibodies or neoexpression of CD9 exert
negative regulatory effects on ADAM17 sheddase activity. Conversely, CD9 silencing increased the activity of ADAM17 against
its substrates TNF-α and ICAM-1. Taken together, our results show that CD9 associates with ADAM17 and, through this interaction,
negatively regulates the sheddase activity of ADAM17. 相似文献
39.
Rodríguez-Muñoz M Sánchez-Blázquez P Vicente-Sánchez A Bailón C Martín-Aznar B Garzón J 《Cellular and molecular life sciences : CMLS》2011,68(17):2933-2949
A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR.
These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic
effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein
1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented
and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive
to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism.
Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength.
Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms
independent of NMDAR. 相似文献
40.
Lopez-Castejón G Baroja-Mazo A Pelegrín P 《Cellular and molecular life sciences : CMLS》2011,68(18):3095-3107
Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage
polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to
the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes
are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified
as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with
PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the
resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study
reveals an additional level of plasticity modulating the resolution of inflammation. 相似文献