11 research outputs found

    Toward high-resolution population genomics using archaeological samples

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    The term ‘ancient DNA’ (aDNA) is coming of age, with over 1,200 hits in the PubMed database, beginning in the early 1980s with the studies of ‘molecular paleontology’. Rooted in cloning and limited sequencing of DNA from ancient remains during the pre-PCR era, the field has made incredible progress since the introduction of PCR and next-generation sequencing. Over the last decade, aDNA analysis ushered in a new era in genomics and became the method of choice for reconstructing the history of organisms, their biogeography, and migration routes, with applications in evolutionary biology, population genetics, archaeogenetics, paleoepidemiology, and many other areas. This change was brought by development of new strategies for coping with the challenges in studying aDNA due to damage and fragmentation, scarce samples, significant historical gaps, and limited applicability of population genetics methods. In this review, we describe the state-of-the-art achievements in aDNA studies, with particular focus on human evolution and demographic history. We present the current experimental and theoretical procedures for handling and analysing highly degraded aDNA. We also review the challenges in the rapidly growing field of ancient epigenomics. Advancement of aDNA tools and methods signifies a new era in population genetics and evolutionary medicine research

    The potential benefits of shRNA-mediated MMP1 silencing for psoriasis

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    Matrix metalloproteinases (MMPs) orchestrate structural remodeling of psoriatic skin and accelerate the development of the inflammatory response. In this paper, we explore whether knocking MMP1 down in epidermal keratinocytes can be beneficial for psoriasis. We discovered that MMP1 silencing with specific shRNA reduced the migration of epidermal keratinocytes and made the cells susceptible to apoptosis in the presence of interferon-γ. Furthermore, MMP1-deficiency partially normalized the expression of genes involved in the pathogenesis of psoriasis (MMP9, -12, CCNA2, CCND1 and KRT17) and the terminal differentiation (KRT1, -10, IVL and LOR). In this respect, MMP1 silencing could be beneficial for psoriasis due to MMP1 expression is limited to psoriatic plaques and correlates with disease severity

    Recent selection of candidate genes for mammal domestication in Europeans and language change in Europe: a hypothesis

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    Background and aim: Human evolution resulted from changes in our biology, behaviour, and culture. One source of these changes has been hypothesised to be our self-domestication (that is, the development in humans of features commonly found in domesticated strains of mammals, seemingly as a result of selection for reduced aggression). Signals of domestication, notably brain size reduction, have increased in recent times. Methods: In this paper, we compare whole-genome data between the Late Neolithic/Bronze Age individuals and modern Europeans. Results: We show that genes associated with mammal domestication and with neural crest development and function are significantly differently enriched in nonsynonymous single nucleotide polymorphisms between these two groups. Conclusion: We hypothesise that these changes might account for the increased features of self-domestication in modern humans and, ultimately, for subtle recent changes in human cognition and behaviour, including language. Keywords: Late Neolithic/Bronze Age; Self-domestication; language change; nonsynonymous SNPs

    Heterogeneous Distribution of Phospholipid Molecular Species in the Surface Culture of <i>Flammulina velutipes</i>: New Facts about Lipids Containing α-Linolenic Fatty Acid

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    Mycelial fungi grow as colonies consisting of polar growing hyphae, developing radially from spore or inoculum. Over time, the colony develops, hyphae are subject to various exogenous or endogenous stimuli, and mycelium becomes heterogeneous in growth, gene expression, biosynthesis, and secretion of proteins and metabolites. Although the biochemical and molecular mechanisms of mycelium heterogeneity have been the subject of many studies, the role of lipids in colony development and zonality is still not understood. This work was undertaken to extend our knowledge of mycelium heterogeneity and to answer the question of how different lipid molecular species are distributed in the surface colony of the basidial fungus Flammulina velutipes and how this distribution correlates with its morphology. The heterogeneity in the lipid metabolism and lipid composition of the fungal mycelium was demonstrated. According to the real-time PCR and LC-MS/MS results, the expression of genes of PC metabolism, accumulation of phospholipid classes, and degree of unsaturation of PC and PE increased in the direction from the center to the periphery of the colony. The peripheral zone of the colony was characterized by a higher value of the PC/PE ratio and a higher level of phospholipids esterified by linolenic acid. Considering that the synthesis of phospholipids in fungi occurs in different ways, we also conducted experiments with deuterium-labeled phospholipid precursors and found out that the Kennedy pathway is the predominant route for PC biosynthesis in F. velutipes. The zonal differences in gene expression and lipid composition can be explained by the participation of membrane lipids in polar growth maintenance and regulation

    Search for Partner Proteins of A. thaliana Immunophilins Involved in the Control of Plant Immunity

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    The involvement of plant immunophilins in multiple essential processes such as development, various ways of adapting to biotic and abiotic stresses, and photosynthesis has already been established. Previously, research has demonstrated the involvement of three immunophilin genes (AtCYP19-1/ROC3, AtFKBP65/ROF2, and AtCYP57) in the control of plant response to invasion by various pathogens. Current research attempts to identify host target proteins for each of the selected immunophilins. As a result, candidate interactors have been determined and confirmed using a yeast 2-hybrid (Y2H) system for protein&ndash;protein interaction assays. The generation of mutant isoforms of ROC3 and AtCYP57 harboring substituted amino acids in the in silico-predicted active sites became essential to achieving significant binding to its target partners. This data shows that ROF2 targets calcium-dependent lipid-binding domain-containing protein (At1g70790; AT1) and putative protein phosphatase (At2g30020; АТ2), whereas ROC3 interacts with GTP-binding protein (At1g30580; ENGD-1) and RmlC-like cupin (At5g39120). The immunophilin AtCYP57 binds to putative pyruvate decarboxylase-1 (Pdc1) and clathrin adaptor complex-related protein (At5g05010). Identified interactors confirm our previous findings that immunophilins ROC3, ROF2, and AtCYP57 are directly involved with stress response control. Further, these findings extend our understanding of the molecular functional pathways of these immunophilins
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