Project description:To investigate the role of TIC in the morning perception process, we performed a transcriptome analysis of the wild type and time for coffee mutant (tic-2) at dawn. An additional file is included. In this file, the expression values for the replicates are condensed in a single data point obtaining one mean and standard deviation of the expression values per genotype. The protocol for this file is: log2 fold change followed by a False Discovery Rate with a p-value equal or below 0.05.
Project description:Neuroblastoma is a pediatric cancer of embryonic origin from neural crest cells. Neuroblastoma has a great medical and social impact because it is occurring with major frequency in pre-scholar age with metastatic disease showing less than 40% of survival at 5-years. In children, metastatic neuroblastoma has very few recurrent mutations but several chromosome structural copy variations. The tumorigenesis of neuroblastoma is still largely unknown; however recently, genomic wide association studies have shown that several gene allelic variants are associated with neuroblastoma predisposition. Many of these gene variants are related to maintaining the chromatin and mitosis integrity. In the present report, I suggest that neuroblastoma predisposing alleles may match by chance influencing the chromatin structure already during the early phases of embryonic life and inducing chromosome instability and structural damages.
Project description:Synchrotron light source facilities worldwide generate terabytes of data in numerous incompatible data formats from a wide range of experiment types. The Data Analysis WorkbeNch (DAWN) was developed to address the challenge of providing a single visualization and analysis platform for data from any synchrotron experiment (including single-crystal and powder diffraction, tomography and spectroscopy), whilst also being sufficiently extensible for new specific use case analysis environments to be incorporated (e.g. ARPES, PEEM). In this work, the history and current state of DAWN are presented, with two case studies to demonstrate specific functionality. The first is an example of a data processing and reduction problem using the generic tools, whilst the second shows how these tools can be targeted to a specific scientific area.
Project description:Cancer, one of the leading causes of death worldwide is estimated to increase to approximately 13.1 million by 2030. This has amplified the research in oncology towards the exploration of novel targets. Recently there has been lots of interest regarding the hedgehog (Hh) pathway, which plays a significant role in the development of organs and tissues during embryonic and postnatal periods. In a normal person, the Hh signaling pathway is under inhibition and gets activated upon the binding of Hh ligand to a transmembrane receptor called Patched (PTCH1) thus allowing the transmembrane protein, smoothened (SMO) to transfer signals through various proteins. One of the newer drugs namely vismodegib involves the inhibition of Hh pathway and has shown promising results in the treatment of advanced basal-cell carcinoma as well as medulloblastoma. It has been granted approval by US Food and Drug Administration's (US FDA) priority review program on January 30, 2012 for the treatment of advanced basal-cell carcinoma. The drug is also being evaluated in malignancies like medulloblastoma, pancreatic cancer, multiple myeloma, chondrosarcoma and prostate cancer. Moreover various Hh inhibitors namely LDE 225, saridegib, BMS 833923, LEQ 506, PF- 04449913 and TAK-441 are also undergoing phase I and II trials for different neoplasms. Hence this review will describe briefly the Hh pathway and the novel drug vismodegib.
Project description:The quest to explain demographic history during the early part of human evolution has been limited because of the scarce paleoanthropological record from the Middle Stone Age. To shed light on the structure of the mitochondrial DNA (mtDNA) phylogeny at the dawn of Homo sapiens, we constructed a matrilineal tree composed of 624 complete mtDNA genomes from sub-Saharan Hg L lineages. We paid particular attention to the Khoi and San (Khoisan) people of South Africa because they are considered to be a unique relic of hunter-gatherer lifestyle and to carry paternal and maternal lineages belonging to the deepest clades known among modern humans. Both the tree phylogeny and coalescence calculations suggest that Khoisan matrilineal ancestry diverged from the rest of the human mtDNA pool 90,000-150,000 years before present (ybp) and that at least five additional, currently extant maternal lineages existed during this period in parallel. Furthermore, we estimate that a minimum of 40 other evolutionarily successful lineages flourished in sub-Saharan Africa during the period of modern human dispersal out of Africa approximately 60,000-70,000 ybp. Only much later, at the beginning of the Late Stone Age, about 40,000 ybp, did introgression of additional lineages occur into the Khoisan mtDNA pool. This process was further accelerated during the recent Bantu expansions. Our results suggest that the early settlement of humans in Africa was already matrilineally structured and involved small, separately evolving isolated populations.
Project description:Herbal products and their formulations have a large market at the global level. A significant portion of the worldwide population relies upon herbal treatment. Their apparent non-toxic and cost-effective nature appeals to the population and drives researchers to pursue them for drug development. However, due to the lack of scientific evidence, their conventional preparation, poor regulation and control make these an unseen threat to the people. There has been a long-standing argument that allopathic medicines are better than herbal medicines due to their specificity and precision. To compete with modern medicines, a concept of science-based phytopharmaceutical drugs was introduced through a draft amendment notified to the Drugs and Cosmetics 1940 and Rules 1945. The amendment has introduced a definition for botanicals and their scientific evaluation for quality safety and efficacy by the Central Drugs Standard and Control Organization (CDSCO) office as a marketing authorization requirement. The present article discusses the advantages and challenges faced in the development of phytopharmaceuticals, and how they differ from dietary supplements and herbal drugs. It also gives consolidated information on Phytopharmaceuticals and their regulatory and Pharmacopoeial status with an exemplary PPI monograph - Aegle marmelos. The plant selection was done based on extensive research using the PRISMA approach. A detailed view of the opportunities and challenges provided by phytopharmaceuticals is explained in the present review.
Project description:Genome regulation in eukaryotes revolves around the nucleosome, the fundamental building block of eukaryotic chromatin. Its constituent parts, the four core histones (H3, H4, H2A, H2B), are universal to eukaryotes. Yet despite its exceptional conservation and central role in orchestrating transcription, repair, and other DNA-templated processes, the origins and early evolution of the nucleosome remain opaque. Histone-fold proteins are also found in archaea, but the nucleosome we know-a hetero-octameric complex composed of histones with long, disordered tails-is a hallmark of eukaryotes. What were the properties of the earliest nucleosomes? Did ancestral histones inevitably assemble into nucleosomes? When and why did the four core histones evolve? This review will look at the evolution of the eukaryotic nucleosome from the vantage point of archaea, focusing on the key evolutionary transitions required to build a modern nucleosome. We will highlight recent work on the closest archaeal relatives of eukaryotes, the Asgardarchaea, and discuss what their histones can and cannot tell us about the early evolution of eukaryotic chromatin. We will also discuss how viruses have become an unexpected source of information about the evolutionary path toward the nucleosome. Finally, we highlight the properties of early nucleosomes as an area where new tools and data promise tangible progress in the not-too-distant future.
Project description:Purpose of reviewDespite high demand, a severe shortage of suitable allografts limits the use of liver transplantation for the treatment of end-stage liver disease. The transplant community is turning to the utilization of high-risk grafts to fill the void. This review summarizes the reemergence of ex-vivo machine perfusion for liver graft preservation, including results of recent clinical trials and its specific role for reconditioning DCD, steatotic and elderly grafts.Recent findingsSeveral phase-1 clinical trials demonstrate the safety and feasibility of machine perfusion for liver graft preservation. Machine perfusion has several advantages compared with static cold storage and may provide superior transplantation outcomes, particularly for marginal grafts. Ongoing multicenter trials aim to confirm the results of preclinical and pilot studies and establish the clinical utility of ex-vivo liver machine perfusion.SummaryMounting evidence supports the benefits of machine perfusion for preservation of liver grafts. Thus, machine perfusion is a promising strategy to expand the donor pool by reconditioning and assessing viability of DCD, elderly and steatotic grafts during the preservation period. Additionally, machine perfusion will serve as a platform to facilitate graft intervention and modification to further optimize marginal grafts.