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101.
Geise Ribeiro Marcel Benadiba Denise de Oliveira Silva Alison Colquhoun 《Cell biochemistry and function》2010,28(1):15-23
The present study reports the synthesis of a novel compound with the formula [Ru2(aGLA)4Cl] according to elemental analyses data, referred to as Ru2GLA. The electronic spectra of Ru2GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru2GLA was synthesized with the aim of combining and possibly improving the anti‐tumour properties of the two active components ruthenium and γ‐linolenic acid (GLA). The properties of Ru2GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru2GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru2GLA enters the cells and ICP‐AES elemental analysis found an increase in ruthenium from <0.02 to 425 mg/Kg in treated cells. The sub‐G1 apoptotic cell population was increased by Ru2GLA (22 ± 5.2%) when analysed by FACS and this was confirmed by Hoechst staining of nuclei. Mitochondrial membrane potential was decreased in the presence of Ru2GLA (44 ± 2.3%). In contrast, the cells which maintained a high mitochondrial membrane potential had an increase (18 ± 1.5%) in reactive oxygen species generation. Both decreased mitochondrial membrane potential and increased reactive oxygen species generation may be involved in triggering apoptosis in Ru2GLA exposed cells. The EC50 for Ru2GLA decreased with increasing time of exposure from 285 µM at 24 h, 211 µM at 48 h to 81 µM at 72 h. In conclusion, Ru2GLA is a novel drug with antiproliferative properties in C6 glioma cells and is a potential candidate for novel therapies in gliomas. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
102.
Many neuropsychiatric disorders exhibit differences in prevalence, age of onset, symptoms or course of illness between males and females. For the most part, the origins of these differences are not well understood. In this article, we provide an overview of sex differences in psychiatric disorders including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), anxiety, depression, alcohol and substance abuse, schizophrenia, eating disorders and risk of suicide. We discuss both genetic and nongenetic mechanisms that have been hypothesized to underlie these differences, including ascertainment bias, environmental stressors, X‐ or Y‐linked risk loci, and differential liability thresholds in males and females. We then review the use of twin, family and genome‐wide association approaches to study potential genetic mechanisms of sex differences and the extent to which these designs have been employed in studies of psychiatric disorders. We describe the utility of genetic epidemiologic study designs, including classical twin and family studies, large‐scale studies of population registries, derived recurrence risks, and molecular genetic analyses of genome‐wide variation that may enhance our understanding sex differences in neuropsychiatric disorders. 相似文献
103.
Koffler Christoph Amor Ben Carbajales-Dale Michael Cascio Joseph Conroy Alison Fava James A. Gaudreault Caroline Gloria Thomas Hensler Connie Horvath Arpad Humbert Sebastien Manzardo Alessandro Margni Manuele Osset Philippe Sinistore Julie Vigon Bruce Wallace Michele L Wang Michael Prox Martina 《The International Journal of Life Cycle Assessment》2020,25(3):478-482
The International Journal of Life Cycle Assessment - 相似文献
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105.
There has been substantial interest of late in using population genetic methods to study sexual conflict, where an allele increases the fitness of one sex at some cost to the other (Mank, 2017). Population genomic scans for sexual conflict offer an important advance given the difficulties of identifying antagonistic alleles from more traditional methods, and could greatly increase our understanding of the extent and loci of sexual conflict. This is particularly true for studies in natural populations, for which obtaining accurate fitness measurements for each sex can be challenging. In this issue of Molecular Ecology, Bissegger, Laurentino, Roesti, and Berner (2019) present a cautionary tale about how to interpret these population genomic data. 相似文献
106.
Alison Shapcott Heather James Laura Simmons Yoko Shimizu Lauren Gardiner David Rabehevitra Rokiman Letsara Stuart Cable John Dransfield William J. Baker Mijoro Rakotoarinivo 《Ecology and evolution》2020,10(6):3120-3137
Madagascar is home to 208 indigenous palm species, almost all of them endemic and >80% of which are endangered. We undertook complete population census and sampling for genetic analysis of a relatively recently discovered giant fan palm, the Critically Endangered Tahina spectablis in 2008 and 2016. Our 2016 study included newly discovered populations and added to our genetic study. We incorporated these new populations into species distribution niche model (SDM) and projected these onto maps of the region. We developed population matrix models based on observed demographic data to model population change and predict the species vulnerability to extinction by undertaking population viability analysis (PVA). We investigated the potential conservation value of reintroduced planted populations within the species potential suitable habitat. We found that the population studied in 2008 had grown in size due to seedling regeneration but had declined in the number of reproductively mature plants, and we were able to estimate that the species reproduces and dies after approximately 70 years. Our models suggest that if the habitat where it resides continues to be protected the species is unlikely to go extinct due to inherent population decline and that it will likely experience significant population growth after approximately 80 years due to the reproductive and life cycle attributes of the species. The newly discovered populations contain more genetic diversity than the first discovered southern population which is genetically depauperate. The species appears to demonstrate a pattern of dispersal leading to isolated founder plants which may eventually lead to population development depending on local establishment opportunities. The conservation efforts currently put in place including the reintroduction of plants within the species potential suitable habitat if maintained are thought likely to enable the species to sustain itself but it remains vulnerable to anthropogenic impacts. 相似文献
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109.
Valentina Ferrari Alison Tarke Hannah Fields Luca Ferrari Trevor Conley Franco Ferrari Zeynep Koşaloğlu-Yalçın Alessandro Sette Bjoern Peters Colin L. McCarthy Asad Bashey Dimitrios Tzachanis Edward D. Ball Tiffany N. Tanaka Rafael Bejar Thomas A. Lane Antonella Vitiello 《Cytotherapy》2021,23(4):320-328
Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden. DNA and RNA from tumor (CD34+) and normal (CD3+) cells isolated from the patients’ blood were sequenced to predict patient-specific MDS neopeptides. Neopeptides representing the somatic variants were used to induce and expand autologous T cells ex vivo, and these were systematically tested in killing assays to determine the proportion of neopeptides yielding neoantigen-specific T cells. The authors identified a total of 32 somatic variants (four to eight per patient) and found that 21 (66%) induced a peptide-specific T-cell response and 19 (59%) induced a T-cell response capable of killing autologous tumor cells. Of the 32 somatic variants, 11 (34%) induced a CD4+ response and 11 (34%) induced a CD8+ response that killed the tumor. These results indicate that in vitro induction of neoantigen-specific T cells is feasible for tumors with very low mutational burden and that this approach warrants investigation as a therapeutic option for such patients. 相似文献
110.
Joshua A. F. Sutton Oliver T. Carnell Lucia Lafage Joe Gray Jacob Biboy Josie F. Gibson Eric J. G. Pollitt Simone C. Tazoll William Turnbull Natalia H. Hajdamowicz Bartomiej Salamaga Grace R. Pidwill Alison M. Condliffe Stephen A. Renshaw Waldemar Vollmer Simon J. Foster 《PLoS pathogens》2021,17(3)
Peptidoglycan is the major structural component of the Staphylococcus aureus cell wall, in which it maintains cellular integrity, is the interface with the host, and its synthesis is targeted by some of the most crucial antibiotics developed. Despite this importance, and the wealth of data from in vitro studies, we do not understand the structure and dynamics of peptidoglycan during infection. In this study we have developed methods to harvest bacteria from an active infection in order to purify cell walls for biochemical analysis ex vivo. Isolated ex vivo bacterial cells are smaller than those actively growing in vitro, with thickened cell walls and reduced peptidoglycan crosslinking, similar to that of stationary phase cells. These features suggested a role for specific peptidoglycan homeostatic mechanisms in disease. As S. aureus missing penicillin binding protein 4 (PBP4) has reduced peptidoglycan crosslinking in vitro its role during infection was established. Loss of PBP4 resulted in an increased recovery of S. aureus from the livers of infected mice, which coincided with enhanced fitness within murine and human macrophages. Thicker cell walls correlate with reduced activity of peptidoglycan hydrolases. S. aureus has a family of 4 putative glucosaminidases, that are collectively crucial for growth. Loss of the major enzyme SagB, led to attenuation during murine infection and reduced survival in human macrophages. However, loss of the other three enzymes Atl, SagA and ScaH resulted in clustering dependent attenuation, in a zebrafish embryo, but not a murine, model of infection. A combination of pbp4 and sagB deficiencies resulted in a restoration of parental virulence. Our results, demonstrate the importance of appropriate cell wall structure and dynamics during pathogenesis, providing new insight to the mechanisms of disease. 相似文献