Establishment of a integrative multi-omics expression database CKDdb in the context of chronic kidney disease (CKD)

Complex human traits such as chronic kidney disease (CKD) are a major health and financial burden in modern societies. Currently, the description of the CKD onset and progression at the molecular level is still not fully understood. Meanwhile, the prolific use of high-throughput omic technologies in disease biomarker discovery studies yielded a vast amount of disjointed data that cannot be easily collated. Therefore, we aimed to develop a molecule-centric database featuring CKD-related experiments from available literature publications. We established the Chronic Kidney Disease database CKDdb, an integrated and clustered information resource that covers multi-omic studies (microRNAs, genomics, peptidomics, proteomics and metabolomics) of CKD and related disorders by performing literature data mining and manual curation. The CKDdb database contains differential expression data from 49395 molecule entries (redundant), of which 16885 are unique molecules (non-redundant) from 377 manually curated studies of 230 publications. This database was intentionally built to allow disease pathway analysis through a systems approach in order to yield biological meaning by integrating all existing information and therefore has the potential to unravel and gain an in-depth understanding of the key molecular events that modulate CKD pathogenesis

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease.

The CABLES1 cell cycle regulator participates in the adrenal-pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing's disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 germline and tumor DNA). Four potentially pathogenic missense variants in CABLES1 were identified, two in young adults (c.532G > A, p.E178K and c.718C > T, p.L240F) and two in children (c.935G > A, p.G312D and c.1388A > G, and p.D463G) with CD; no CNVs were found. The four variants affected residues within or close to the predicted cyclin-dependent kinase-3 (CDK3)-binding region of the CABLES1 protein and impaired its ability to block cell growth in a mouse corticotropinoma cell line (AtT20/D16v-F2). The four patients had macroadenomas. We provide evidence for a role of CABLES1 as a novel pituitary tumor-predisposing gene. Its function might link two of the main molecular mechanisms altered in corticotropinomas: the cyclin-dependent kinase/cyclin group of cell cycle regulators and the epidermal growth factor receptor signaling pathway. Further studies are needed to assess the prevalence of CABLES1 mutations among patients with other types of pituitary adenomas and to elucidate the pituitary-specific functions of this gene

The normalization of the United States-Libya relations, 2003-2006

The purpose of this study is to examine and analyze the factors leading to the normalized relations between the United States (U.S.) and Libya in 2003–2006. The theoretical framework of this study was the rational actor model of foreign policy decision making, which held that the foreign policy decisions were made in such a way as to maximize benefits while minimizing costs. The study was divided into three parts. The first part looked at the political factors leading to the normalized relations between the two countries. These factors include the diplomatic, leadership and media. The second part looked at the economic factors such as the oil and economic sanctions. The last part looked at the security factors including terrorism and weapons of mass destruction, and the Libya‘s attitudes towards Israel. The data for this study were collected mainly from both primary and secondary sources. The primary sources included documents, agreements, and treaties that signed by Libya with the U.S. In addition, the researcher analyzed the outputs of the U.S. and Libyan policy- makers and institutions relating to the research topic, such as speeches, official correspondences, decrees, and decisions of both governments relating to each other. Interviews with knowledgeable people were also conducted. The secondary sources included books, journals, magazines and newspapers. Key findings over the period studied indicated the importance of the political, economic, and security factors in forwarding the U.S. policy options towards the normalization of the U.S. - Libya relations in 2006. Furthermore, this study also concluded that the success of the normalized relations was a product of intertwining of these factors together through their influences on policy- makers of both countries to take flexible attitudes to resolve outstanding issues between them

Influence of R. Nixon – J. Ford’s nuclear non-proliferation policy on the leading countries of Western Europe (1969–1975)

Выявляется степень влияния проводимой администрациями Р. Никсона и Дж. Форда политики ядерного нераспространения на отношения США с ведущими странами Западной Европы в 1969–1975 гг. Про-анализированы позиции правительств Великобритании и Франции в отношении политики нераспространения ядерного оружия. Особое внимание уделяется внешнеполитическому курсу ФРГ, в том числе связи подписания и ратификации Бонном Договора о нераспространении ядерного оружия с «новой восточной политикой» В. Брандта

OrthoDB: a hierarchical catalog of animal, fungal and bacterial orthologs

The concept of orthology provides a foundation for formulating hypotheses on gene and genome evolution, and thus forms the cornerstone of comparative genomics, phylogenomics and metagenomics. We present the update of OrthoDB—the hierarchical catalog of orthologs (http://www.orthodb.org). From its conception, OrthoDB promoted delineation of orthologs at varying resolution by explicitly referring to the hierarchy of species radiations, now also adopted by other resources. The current release provides comprehensive coverage of animals and fungi representing 252 eukaryotic species, and is now extended to prokaryotes with the inclusion of 1115 bacteria. Functional annotations of orthologous groups are provided through mapping to InterPro, GO, OMIM and model organism phenotypes, with cross-references to major resources including UniProt, NCBI and FlyBase. Uniquely, OrthoDB provides computed evolutionary traits of orthologs, such as gene duplicability and loss profiles, divergence rates, sibling groups, and now extended with exon-intron architectures, syntenic orthologs and parent-child trees. The interactive web interface allows navigation along the species phylogenies, complex queries with various identifiers, annotation keywords and phrases, as well as with gene copy-number profiles and sequence homology searches. With the explosive growth of available data, OrthoDB also provides mapping of newly sequenced genomes and transcriptomes to the current orthologous group

Prospectus, December 5, 2019

‘TIS THE SEASON TO ACE FINALS; Parkland Theatre gets into the spirit with A Christmas Carol; Happy holidays, joyeuses fêtes, felices vacaciones; College Student Wishlist: Student Discounts; Letter to the Editor: Thank You Parkland!; Meet the staff: Sidney Mounts; Holiday Movies: Traditions, praises & critiques; The history of the holiday seasonhttps://spark.parkland.edu/prospectus_2019/1051/thumbnail.jp

Multi-omic detection of Mycobacterium leprae in archaeological human dental calculus

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record.publishedVersio