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71.
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Carrasco-Marín E Fernández-Prieto L Rodriguez-Del Rio E Madrazo-Toca F Reinheckel T Saftig P Alvarez-Dominguez C 《The Journal of biological chemistry》2011,286(5):3332-3341
The innate immune response to Listeria monocytogenes depends on phagosomal bacterial degradation by macrophages. Here, we describe the role of LIMP-2, a lysosomal type III transmembrane glycoprotein and scavenger-like protein, in Listeria phagocytosis. LIMP-2-deficient mice display a macrophage-related defect in Listeria innate immunity. They produce less acute phase pro-inflammatory cytokines/chemokines, MCP-1, TNF-α, and IL-6 but normal levels of IL-12, IL-10, and IFN-γ and a 25-fold increase in susceptibility to Listeria infection. This macrophage defect results in a low listericidal potential, poor response to TNF-α activation signals, impaired phago-lysosome transformation into antigen-processing compartments, and uncontrolled LM cytosolic growth that fails to induce normal levels of acute phase pro-inflammatory cytokines. LIMP-2 transfection of CHO cells confirmed that LIMP-2 participates in the degradation of Listeria within phagosomes, controls the late endosomal/lysosomal fusion machinery, and is linked to the activation of Rab5a. Therefore, the role of LIMP-2 appears to be connected to the TNF-α-dependent and early activation of Listeria macrophages through internal signals linking the regulation of late trafficking events with the onset of the innate Listeria immune response. 相似文献
74.
Carlos Albuquerque Francisco Morinha João Requicha Isabel Dias Henrique Guedes-Pinto Carlos Viegas Estela Bastos 《Gene》2014
Periodontal disease (PD) refers to a group of inflammatory diseases that affect the periodontium, the organ which surrounds and supports the teeth. PD is a highly prevalent disease with a multifactorial etiology and, in humans the individual susceptibility is known to be strongly determined by genetic factors. Several candidate genes have been studied, namely genes related with molecules involved in the inflammatory response. Interleukin-10 (IL-10) is a cytokine with important anti-inflammatory and immunomodulatory roles, and several studies indicate an association between IL10 polymorphisms and PD. In dogs, an important animal model in periodontology, PD is also a highly prevalent naturally occurring disease, and only now are emerging the first studies evaluating the genetic predisposition. In this case–control study, a population of 90 dogs (40 dogs with PD and 50 healthy dogs) was used to study the IL10 gene, and seven new genetic variations in this gene were identified. No statistically significant differences were detected in genotype and allele frequencies of these variations between the PD cases and control groups. Nevertheless, one of the variations (IL10/2_g.285G > A) leads to an amino acid change (glycine to arginine) in the putative signal peptide, being predicted a potential influence on IL-10 protein functionality. Further investigations are important to clarify the biological importance of these new findings. The knowledge of these genetic determinants can help to understand properly the complex causal pathways of PD, with important clinical implications. 相似文献
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76.
Maria das Neves Paiva-Cardoso Francisco Morinha Paulo Barros Hélia Vale-Gonçalves Ana Cláudia Coelho Lisete Fernandes Paulo Travassos Ana Sofia Faria Estela Bastos Mário Santos João Alexandre Cabral 《European Journal of Wildlife Research》2014,60(4):645-649
The psychrophilic fungus Pseudogymnoascus destructans (formerly known as Geomyces destructans) is considered the etiological agent of white-nose disease (WND), an emerging disease which affects bats during their hibernation period. This disease is clinically characterized by the growth of a white fungus on muzzle, ears, and wings’ membranes of affected bats. This infection caused the death of several million bats in North America. Conversely, European bats show no evidence of significant mortality occurrences associated with P. destructans colonization. This fungus has been isolated from bats in at least 15 European countries since 2008, but was never before reported in the Iberian Peninsula. This study describes the first case report of P. destructans colonization in bats from Portugal. We isolated P. destructans from three hibernating Myotis blythii (lesser mouse-eared bat) with visual signs of P. destructans colonization, during a routine visit to a mine located in the Trás-os-Montes region, Northern Portugal. M. blythii is one of the rarest bat species in Europe, classified as critically endangered in Portugal. P. destructans was obtained from at least three different parts of the body of each specimen analyzed. The identification of the respective fungal isolates was based on the macroscopic and microscopic characterization of the cultures and confirmed by PCR-based analysis. All nucleotide sequences obtained showed 100 % identity with previous data reported for P. destructans. This new finding improves the current knowledge about the European distribution of P. destructans, which is of great interest for forthcoming studies on the fungus dispersion and impact among bat populations at regional and/or global level. 相似文献
77.
Estela Natacha Brandt Busanello Vannessa Gonçalves Araujo Lobato Ângela Zanatta Carolina Maso Viegas César Augusto João Ribeiro Moacir Wajner 《Life sciences》2014
Aims
Peroxisomal biogenesis disorders (PBD) are inherited disorders clinically manifested by neurological symptoms and brain abnormalities, in which the cerebellum is usually involved. Biochemically, patients affected by these neurodegenerative diseases accumulate branched-chain fatty acids, including pristanic acid (Prist) in the brain and other tissues.Main methods
In the present investigation we studied the in vitro influence of Prist, at doses found in PBD, on oxidative phosphorylation, by measuring the activities of the respiratory chain complexes I–IV and ATP production, as well as on creatine kinase and synaptic Na+, K+-ATPase activities in rat cerebellum.Key findings
Prist significantly decreased complexes I–III (65%), II (40%) and especially II–III (90%) activities, without altering the activities of complex IV of the respiratory chain and creatine kinase. Furthermore, ATP formation and synaptic Na+, K+-ATPase activity were markedly inhibited (80–90%) by Prist. We also observed that this fatty acid altered mitochondrial and synaptic membrane fluidity that may have contributed to its inhibitory effects on the activities of the respiratory chain complexes and Na+, K+-ATPase.Significance
Considering the importance of oxidative phosphorylation for mitochondrial homeostasis and of Na+, K+-ATPase for the maintenance of cell membrane potential, the present data indicate that Prist compromises brain bioenergetics and neurotransmission in cerebellum. We postulate that these pathomechanisms may contribute to the cerebellar alterations observed in patients affected by PBD in which Prist is accumulated. 相似文献78.
The distribution of the two glutamate-synthase (GOGAT) activities known to exist in higher plants (NADH dependent, EC 2.6.1.53; and ferredoxin dependent, EC 1.4.7.1) was studied in non-chlorophyllous and chlorophyllous cultured tissue as well as in young leaves of Bouvardia ternifolia. The NADH-GOGAT was present in all three tissues. Using a sucrose gradient we found it in both the soluble and the plastid fraction of non-chlorophyllous and chlorophyllous tissue, but exclusively in the chloroplast fraction of the leaves. Ferredoxin-GOGAT was found only in green tissues and was confined to the chloroplasts. Ferredoxin-GOGAT activity increased in parallel with the chlorophyll content of the callus during the greening process in Murashige-Skoog medium (nitrate and ammonium as the nitrogen sources), while NADH-GOGAT was not affected by the greening process in this medium. Furthermore, both activities were differentially affected by either nitrate or ammonium as the sole nitrogen source in the medium during this process. It is suggested that each GOGAT activity is a different entity or is differently regulated.Abbreviations GOGAT
glutamate synthase
- MS
Murashige-Skoog (1962) medium
- PMSF
phenylmethylsulfonyl fluoride 相似文献
79.
On 10 rocky outcrops with mountain vizcacha colonies, diets and trophic relations of five predator species were analyzed to evaluate their impact in vizcacha populations. Diets included 17 prey items of which mammals represented 97% of biomass. Lagomorphs were the most important prey, followed by sigmodontines, tuco-tucos, and mountain vizcachas. The Barn Owl was a specialized predator, while the culpeo and lesser grison were generalized consumers. Predation of mountain vizcacha by Magellanic Horned Owls and culpeo foxes could increase vizcacha vulnerability because vizcacha populations are small and fragmented, and females produce only one offspring per year. 相似文献
80.
Marc D Tambini Marta Pera Ellen Kanter Hua Yang Cristina Guardia‐Laguarta David Holtzman David Sulzer Estela Area‐Gomez Eric A Schon 《EMBO reports》2016,17(1):27-36
In addition to the appearance of senile plaques and neurofibrillary tangles, Alzheimer''s disease (AD) is characterized by aberrant lipid metabolism and early mitochondrial dysfunction. We recently showed that there was increased functionality of mitochondria‐associated endoplasmic reticulum (ER) membranes (MAM), a subdomain of the ER involved in lipid and cholesterol homeostasis, in presenilin‐deficient cells and in fibroblasts from familial and sporadic AD patients. Individuals carrying the ε4 allele of apolipoprotein E (ApoE4) are at increased risk for developing AD compared to those carrying ApoE3. While the reason for this increased risk is unknown, we hypothesized that it might be associated with elevated MAM function. Using an astrocyte‐conditioned media (ACM) model, we now show that ER–mitochondrial communication and MAM function—as measured by the synthesis of phospholipids and of cholesteryl esters, respectively—are increased significantly in cells treated with ApoE4‐containing ACM as compared to those treated with ApoE3‐containing ACM. Notably, this effect was seen with lipoprotein‐enriched preparations, but not with lipid‐free ApoE protein. These data are consistent with a role of upregulated MAM function in the pathogenesis of AD and may help explain, in part, the contribution of ApoE4 as a risk factor in the disease. 相似文献