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Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture

Sample selection and data harmonization

The 2075 samples collected for Dog10K were selected to represent a wide variety of breeds of differing morphology, history, and behavior (1649 samples); dogs that represent local niche populations or breeds that are not nationally registered (18 samples); village dogs from multiple locations (336 samples); and wild canids (68 wolves, 4 coyotes) (Fig. 1, Additional file 1: Table S1). At the time of collection, breed samples were free from known disease, and efforts were made to balance sex across all populations (52.6% female).

Overview of the Dog10K collection. a Sample collection and sample filtering for (b) the varied demographic, genome function, and architecture examined in the program. QC, quality control. ROH, runs of homozygosity. OMIA, Online Mendelian Inheritance in Animals

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A reference genome consisting of the German Shepherd Dog genome assembly [30] (UU_Cfam_GSD_1.0, G

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Abstract

The therapeutic potential of the mesenchymal stromal cell (MSC) secretome, consisting of all molecules secreted by MSCs, is intensively studied. MSCs can be readily isolated, expanded, and manipulated in culture, and few people argue with the ethics of their collection. Despite promising pre-clinical studies, most MSC secretome-based therapies have not been implemented in human medicine, in part because the complexity of bioactive factors secreted by MSCs is not completely understood. In addition, the MSC secretome is variable, influenced by individual donor, tissue source of origin, culture conditions, and passage. An increased understanding of the factors that make up the secretome and the ability to manipulate MSCs to consistently secrete factors of biologic importance will improve MSC therapy. To aid in this goal, we can draw from the wealth of information available on secreted factors from MSC isolated from veterinary species. These translational animal models will inspire efforts to move human MSC secretome therapy from bench to bedside.

Keywords: mesenchymal st

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The study shows that cholesterol modulates IFNG expression in CD4⁺ T cells via SGK1 activation, suggesting lipid pathways as potential targets for regulating immune responses in the CNS.

Abstract

IFNγ-secreting T cells are central for the maintenance of immune surveillance within the central nervous system (CNS). It was previously reported in healthy donors that the T-cell environment in the CNS induces distinct signatures related to cytotoxic capacity, CNS trafficking, tissue adaptation, and lipid homeostasis. These findings suggested that the CNS milieu consisting predominantly of lipids mediated the metabolic conditions leading to IFNγ-secreting brain CD4 T cells. Here, we demonstrate that the supplementation of CD4⁺CD45RO⁺CXCR3⁺ cells with cholesterol modulates their function and increases IFNG expression. The heightened IFNG expression was mediated by the activation of the serum/glucocorticoid-regulated kinase (SGK1). Inhibition of SGK1 by a specific enzymatic inhibitor significantly reduces the expression of IFNG. Our results confirm the crucial role of li