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351.
Response to acute nickel toxicity in rats as a function of sex 总被引:1,自引:0,他引:1
Summary The effects of different nickel chloride doses upon blood and plasma glucose and essential metal homeostasis were studied in male and female rats. A definite sex-dependent response to injections of nickel has been observed for both the increase in plasma and blood glucose levels and the time at which these levels peak. Males showed a fast recovery from the rise in glucose levels and were much less affected by changes in the other parameters studied. In females, an extended rise in glucose levels was observed. All these effects are clearly nickel dose-dependent. Plasma, liver and kidney copper levels rose significantly in females while only a small decrease was observed in male kidneys. Zinc levels rose in all organs studied but males recovered to basal levels after the study period, whereas females maintained maximum levels at the end of the same period. An increase in urinary excretion of iron was observed. The present results show that the sex differences to acute nickel toxicity can be a helpful way to study metal interaction and discriminate between specific toxicity due to nickel or that induced by the associated hyperglucagonemia. 相似文献
352.
Christian Dupont Albertus Viljoen Faustine Dubar Mickaël Blaise Audrey Bernut Alexandre Pawlik Christiane Bouchier Roland Brosch Yann Guérardel Joël Lelièvre Lluis Ballell Jean‐Louis Herrmann Christophe Biot Laurent Kremer 《Molecular microbiology》2016,101(3):515-529
The natural resistance of Mycobacterium abscessus to most commonly available antibiotics seriously limits chemotherapeutic treatment options, which is particularly challenging for cystic fibrosis patients infected with this rapid‐growing mycobacterium. New drugs with novel molecular targets are urgently needed against this emerging pathogen. However, the discovery of such new chemotypes has not been appropriately performed. Here, we demonstrate the utility of a phenotypic screen for bactericidal compounds against M. abscessus using a library of compounds previously validated for activity against M. tuberculosis. We identified a new piperidinol‐based molecule, PIPD1, exhibiting potent activity against clinical M. abscessus strains in vitro and in infected macrophages. Treatment of infected zebrafish with PIPD1 correlated with increased embryo survival and decreased bacterial burden. Whole genome analysis of M. abscessus strains resistant to PIPD1 identified several mutations in MAB_4508, encoding a protein homologous to MmpL3. Biochemical analyses demonstrated that while de novo mycolic acid synthesis was unaffected, PIPD1 strongly inhibited the transport of trehalose monomycolate, thereby abrogating mycolylation of arabinogalactan. Mapping the mutations conferring resistance to PIPD1 on a MAB_4508 tridimensional homology model defined a potential PIPD1‐binding pocket. Our data emphasize a yet unexploited chemical structure class against M. abscessus infections with promising translational development possibilities. 相似文献
353.
Matthieu Deschamps Guillaume Laval Maud Fagny Yuval Itan Laurent Abel Jean-Laurent Casanova Etienne Patin Lluis Quintana-Murci 《American journal of human genetics》2016,98(1):5-21
Human genes governing innate immunity provide a valuable tool for the study of the selective pressure imposed by microorganisms on host genomes. A comprehensive, genome-wide study of how selective constraints and adaptations have driven the evolution of innate immunity genes is missing. Using full-genome sequence variation from the 1000 Genomes Project, we first show that innate immunity genes have globally evolved under stronger purifying selection than the remainder of protein-coding genes. We identify a gene set under the strongest selective constraints, mutations in which are likely to predispose individuals to life-threatening disease, as illustrated by STAT1 and TRAF3. We then evaluate the occurrence of local adaptation and detect 57 high-scoring signals of positive selection at innate immunity genes, variation in which has been associated with susceptibility to common infectious or autoimmune diseases. Furthermore, we show that most adaptations targeting coding variation have occurred in the last 6,000–13,000 years, the period at which populations shifted from hunting and gathering to farming. Finally, we show that innate immunity genes present higher Neandertal introgression than the remainder of the coding genome. Notably, among the genes presenting the highest Neandertal ancestry, we find the TLR6-TLR1-TLR10 cluster, which also contains functional adaptive variation in Europeans. This study identifies highly constrained genes that fulfill essential, non-redundant functions in host survival and reveals others that are more permissive to change—containing variation acquired from archaic hominins or adaptive variants in specific populations—improving our understanding of the relative biological importance of innate immunity pathways in natural conditions. 相似文献
354.
355.
Carlos López Joaquín Jaén Martinez Marylène Lejeune Patricia Escrivà Maria T. Salvadó Lluis E. Pons Tomás Álvaro Jordi Baucells Marcial García-Rojo Xavier Cugat Ramón Bosch 《Histochemistry and cell biology》2009,132(4):469-477
The volume of digital image (DI) storage continues to be an important problem in computer-assisted pathology. DI compression enables the size of files to be reduced but with the disadvantage of loss of quality. Previous results indicated that the efficiency of computer-assisted quantification of immunohistochemically stained cell nuclei may be significantly reduced when compressed DIs are used. This study attempts to show, with respect to immunohistochemically stained nuclei, which morphometric parameters may be altered by the different levels of JPEG compression, and the implications of these alterations for automated nuclear counts, and further, develops a method for correcting this discrepancy in the nuclear count. For this purpose, 47 DIs from different tissues were captured in uncompressed TIFF format and converted to 1:3, 1:23 and 1:46 compression JPEG images. Sixty-five positive objects were selected from these images, and six morphological parameters were measured and compared for each object in TIFF images and those of the different compression levels using a set of previously developed and tested macros. Roundness proved to be the only morphological parameter that was significantly affected by image compression. Factors to correct the discrepancy in the roundness estimate were derived from linear regression models for each compression level, thereby eliminating the statistically significant differences between measurements in the equivalent images. These correction factors were incorporated in the automated macros, where they reduced the nuclear quantification differences arising from image compression. Our results demonstrate that it is possible to carry out unbiased automated immunohistochemical nuclear quantification in compressed DIs with a methodology that could be easily incorporated in different systems of digital image analysis. 相似文献
356.
357.
Raül Ramos Francisco Ramírez Carolina Sanpera Lluís Jover Xavier Ruiz 《Journal of Ornithology》2009,150(1):265-272
In recent decades, the Yellow-legged Gull (Larus michahellis) has become a problematic species in many Mediterranean countries, mainly because it interferes with human interests. However,
this gull also has a negative impact on several other bird species, many of which are classified as endangered. Two different
European Union Action Plans are currently under development with the aim of decreasing the availability of food derived from
human activities, such as garbage and fishery discards, which are considered to be the main causes of the superpopulations
of this gull. Here, we describe the diet of Yellow-legged Gull chicks, with particular emphasis on establishing the dependence
of each population on refuse dumps, in order to forecast changes in gull population dynamics in response to the management
decisions being implemented. We sampled four colonies along the Western Mediterranean in Spain: the Medes Islands, the Ebro
Delta, the Columbretes Islands, and Mazarrón Island. To elucidate their feeding ecology and to avoid obtaining a discrete
estimation from a single sampling, we collected regurgitates from each colony three times throughout the chick-rearing period.
Slightly differential feeding habits were observed between chick age classes. Younger chicks in all four colonies tended to
be consistently provisioned with smaller prey such as invertebrates. Distinct uses of several foraging habitats among localities
were observed. In particular, the use of refuse dumps was common and abundant in two of the colonies: the Medes and Mazarrón
Islands. As a consequence of current management strategies, generalized reductions in Yellow-legged Gull populations and increases
in the consumption of alternative food resources to those of fishery discards and refuse scraps are expected. Finally, we
predict that decreased food availability will force some gulleries to increase predation on endangered species, thereby raising
a conservation concern.
X. Ruiz: deceased on 27 April 2008. 相似文献
358.
359.
Josep M. Lluis Laura Llacuna Claudia von Montfort Cristina Bárcena Carlos Enrich Albert Morales José C. Fernandez-Checa 《PloS one》2009,4(11)
Background
Hypoxia-mediated HIF-1α stabilization and NF-κB activation play a key role in carcinogenesis by fostering cancer cell survival, angiogenesis and tumor invasion. Gangliosides are integral components of biological membranes with an increasingly recognized role as signaling intermediates. In particular, ganglioside GD3 has been characterized as a proapoptotic lipid effector by promoting cell death signaling and suppression of survival pathways. Thus, our aim was to analyze the role of GD3 in hypoxia susceptibility of hepatocarcinoma cells and in vivo tumor growth.Methodology/Principal Findings
We generated and characterized a human hepatocarcinoma cell line stably expressing GD3 synthase (Hep3B-GD3), which catalyzes the synthesis of GD3 from GM3. Despite increased GD3 levels (2–3 fold), no significant changes in cell morphology or growth were observed in Hep3B-GD3 cells compared to wild type Hep3B cells under normoxia. However, exposure of Hep3B-GD3 cells to hypoxia (2% O2) enhanced reactive oxygen species (ROS) generation, resulting in decreased cell survival, with similar findings observed in Hep3B cells exposed to increasing doses of exogenous GD3. In addition, hypoxia-induced c-Src phosphorylation at tyrosine residues, NF-κB activation and subsequent expression of Mn-SOD were observed in Hep3B cells but not in Hep3B-GD3 cells. Moreover, MnTBAP, an antioxidant with predominant SOD mimetic activity, reduced ROS generation, protecting Hep3B-GD3 cells from hypoxia-induced death. Finally, lower tumor growth, higher cell death and reduced Mn-SOD expression were observed in Hep3B-GD3 compared to Hep3B tumor xenografts.Conclusion
These findings underscore a role for GD3 in hypoxia susceptibility by disabling the c-Src/NF-κB survival pathway resulting in lower Mn-SOD expression, which may be of relevance in hepatocellular carcinoma therapy. 相似文献360.
Jesús Villar Lina Pérez-Méndez Elena Espinosa Carlos Flores Jesús Blanco Arturo Muriel Santiago Basaldúa Mercedes Muros Lluis Blanch Antonio Artigas Robert M. Kacmarek for the GRECIA GEN-SEP groups 《PloS one》2009,4(8)