1,252 research outputs found

    Bacterial NadQ (COG4111) is a Nudix-like, ATP-responsive regulator of NAD biosynthesis

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    Nicotinamide-adenine dinucleotide (NAD) is centrally important to metabolic reactions that involve redox chemistry. In bacteria, NAD biosynthesis is controlled by different transcription factors, depending on the species. Among the four regulators identified so far, the protein NadQ is reported to act as a repressor of the de novo NAD biosynthetic pathway in proteobacteria. Using comparative genomics, a systematic reconstruction of NadQ regulons in thousands of fully sequenced bacterial genomes has been performed, confirming that NadQ is present in α-proteobacteria and some β- and γ-proteobacteria, including pathogens like Bordetella pertussis and Neisseria meningitidis, where it likely controls de novo NAD biosynthesis. Through mobility shift assay and mutagenesis, the DNA binding activity of NadQ from Agrobacterium tumefaciens was experimentally validated and determined to be suppressed by ATP. The crystal structures of NadQ in native form and in complex with ATP were determined, indicating that NadQ is a dimer, with each monomer composed of an N-terminal Nudix domain hosting the effector binding site and a C-terminal winged helix-turn-helix domain that binds DNA. Within the dimer, we found one ATP molecule bound, at saturating concentration of the ligand, in keeping with an intrinsic asymmetry of the quaternary structure. Overall, this study provided the basis for depicting a working model of NadQ regulation mechanism

    The Zur regulon of Corynebacterium glutamicum ATCC 13032

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    Schröder J, Jochmann N, Rodionov DA, Tauch A. The Zur regulon of Corynebacterium glutamicum ATCC 13032. BMC Genomics. 2010;11(1): 12.Background Zinc is considered as an essential element for all living organisms, but it can be toxic at large concentrations. Bacteria therefore tightly regulate zinc metabolism. The Cg2502 protein of Corynebacterium glutamicum was a candidate to control zinc metabolism in this species, since it was classified as metalloregulator of the zinc uptake regulator (Zur) subgroup of the ferric uptake regulator (Fur) family of DNA-binding transcription regulators. Results The cg2502 (zur) gene was deleted in the chromosome of C. glutamicum ATCC 13032 by an allelic exchange procedure to generate the zur-deficient mutant C. glutamicum JS2502. Whole-genome DNA microarray hybridizations and real-time RT-PCR assays comparing the gene expression in C. glutamicum JS2502 with that of the wild-type strain detected 18 genes with enhanced expression in the zur mutant. The expression data were combined with results from cross-genome comparisons of shared regulatory sites, revealing the presence of candidate Zur-binding sites in the mapped promoter regions of five transcription units encoding components of potential zinc ABC-type transporters (cg0041-cg0042/cg0043; cg2911-cg2912-cg2913), a putative secreted protein (cg0040), a putative oxidoreductase (cg0795), and a putative P-loop GTPase of the COG0523 protein family (cg0794). Enhanced transcript levels of the respective genes in C. glutamicum JS2502 were verified by real-time RT-PCR, and complementation of the mutant with a wild-type zur gene reversed the effect of differential gene expression. The zinc-dependent expression of the putative cg0042 and cg2911 operons was detected in vivo with a gfp reporter system. Moreover, the zinc-dependent binding of purified Zur protein to double-stranded 40-mer oligonucleotides containing candidate Zur-binding sites was demonstrated in vitro by DNA band shift assays. Conclusion Whole-genome expression profiling and DNA band shift assays demonstrated that Zur directly represses in a zinc-dependent manner the expression of nine genes organized in five transcription units. Accordingly, the Zur (Cg2502) protein is the key transcription regulator for genes involved in zinc homeostasis in C. glutamicum

    Outstanding Surgeon and Scientist Dmitry Alekseevich Arapov

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    In 2022, we are approaching 125 years since the birth of Dmitry Alekseevich Arapov, a prominent domestic surgeon, scientist, experimenter, organizer of the military medical services. Dmitry A. Arapov, one of the most prominent representatives of the S.S. Yudin scientific school, worked at the N.V. Sklifosovsky Research Institute for Emergency Medicine from 1929 till 1984. He quickly proved himself not only as an excellent doctor and a skilled surgeon, but also as a researcher, and soon became one of the closest students and associates of S.S. Yudin. Dmitry A. Arapov drafted as a field surgeon during the Soviet-Finnish war of 1939-1940, from the first to the last day he went through the Great Patriotic War, being the Head of the surgical service of the Northern Fleet in Polyarny. In this position, he significantly improved the system for providing emergency surgical care on ships and in naval hospitals, based on the experience gained over the years of work at the N.V. Sklifosovsky Research Institute for Emergency Medicine. From July 1950 Dmitry A. Arapov was Chief Surgeon of the USSR Navy, from May 1953 he was Deputy Chief surgeon of the Main Military Sanitary Directorate of the USSR Ministry of Defense, and from May 1955 again Chief Surgeon of the USSR Navy, until his retirement in October, 1968. At the same time, Dmitry A. Arapov did not leave his work at the N.V. Sklifosovsky Research Institute for Emergency Medicine until the last days of his life. Dmitry A. Arapov is the author of more than 200 research papers, including 14 monographs. Scientific interests of Dmitry A. Arapov went far beyond emergency surgery, to which he naturally paid most attention. His works are devoted to various issues of military and emergency surgery of the abdominal and thoracic organs, topical issues of burn injuries, surgical site infections, reconstructive surgery, neurosurgery, treatment of endocrine disorders, and anesthesiology and resuscitation. Also Dmitry A. Arapov successfully dealt with the problems of autotransfusion, blood reinfusion from the chest and abdomen, transfusion of fibrinolytic blood. The main directions of scientific research, laid down by Dmitry A. Arapov, are currently being continued at the Scientific Department of Emergency Surgery, Endoscopy and Intensive Care of the N.V. Sklifosovsky Research Institute for Emergency Medicine. Memory of Dmitry A. Arapov has been preserved to this day. To the 100th anniversary of the birth of D.A. Arapov, a scientific conference was held at our Institute. The naval hospital in the town of Polyarny, Murmansk region, was named after Dmitry A. Arapov, and in honor of D.A. Arapov, a memorial plaque was installed on its building. In the 70s of the twentieth century, People’s Artist of the USSR L.E. Kerbel created a sculpture of Dmitry A. Arapov, which was stored in the local history museum of the town of Polyarny. His bust portrait (by artist T.S. Smagina) is exhibited at the Scientific Department of Emergency Surgery, Endoscopy and Intensive Care of the N.V. Sklifosovsky Research Institute for Emergency Medicine. In addition, the N.V. Sklifosovsky Research Institute for Emergency Medicine owns an earlier portrait of Dmitry A. Arapov by artist F.S. Bulgak. We introduce these portraits into scientific circulation for the first time. We are confident that they will be able to tell contemporaries a lot about this scientist, surgeon and man who made a great contribution to surgery and military medicine, and rightfully entered the history of Russian medicine

    A multi-lepton search for new physics in 35pb⁻¹ proton-proton collisions at the LHC for a center of mass energy of √s = 7 TeV using the CMS detector

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    This thesis describes a model independent search for new physics with a decay signature of three or more leptons and missing transverse energy in 35pb⁻¹ of proton-proton collisions at the LHC at a center mass energy √s = 7 TeV using the CMS detector. Standard Model backgrounds are predicted using both simulations and collision data. The observed events are consistent with the Standard Model predictions. The results are interpreted using various supersymmetric models: gravity mediated symmetry breaking, gauge mediated symmetry breaking with slepton co-NLSP, and leptonic R-parity violating.Ph. D.Includes bibliographical referencesby Dmitry Hit

    Writing the Time of Troubles, False Dmitry in Russian Literature (Book Review)

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    This book discusses the Time of Troubles (Smutnoe vremya) period and the pretenders who appeared after the killing of Ivan the Terrible’s legal heir, Ivan, leaving the Empire without leadership. The power struggle began immediately after the death of Tsar Ivan which brought the Rurikid dynasty to an end; rival boyars created a weak government and autocracy. The book discusses these issues and the representations of Dmitry, the son of Ivan the Terrible within the context of Russian literature. The absence of legitimate royal authority after the demise of the Rurikid dynasty in 1598 caused a dynastic crisis. This period known as the Time of Troubles was characterized by a dynastic struggle that nearly resulted in the shattering of the Muscovite state. It finally came to an end in 1613 with the appearance of the new dynasty, the Romanovs. The book consists of six chapter. In the Introduction the author states that she will examine the “protagonist”, Dmitry, within the context of Russian literature. She examines Dmitry both as a literary figure and a real historical one, and describes Dmitry as a “tabula rasa” because he died under mysterious circumstances with no credible witnesses to confirm how he died. In her book, the author conducts her research both chronologically and diachronically. Chapter I is an introductory chapter that provides information on the eighteenth and nineteenth-century Russian texts Tulupov’s Life of St. Dmitry, The Story of Grishka Otrepev and Tale of Recovery that illustrate the prehistory of Dmitry. The author compares seventeenth century text types and arrives at the conclusion that all three works express a political message and that all of them contain a hagiographical structure and explication. Chapter II examines Russia’s historical experience in the eighteenth century and its literary tradition. In this chapter, the author examines Sumarokov’s tragedy Dmitry the Pretender and Narezhny’s Dmitry the Pretender. The author compares the main causes of his usurpation and its interpretation in literary works of the seventeenth century and the eighteenth century, and concludes that the writers of the seventeenth century crafted quasi-literary, polemical, monological interpretations of the period and determined who was the sole man qualified to rule. Prose treatments of the Dmitry material were the most appropriate way to shape their literature. Eighteenth century writers, on the other hand, recognized a large number of candidates to the throne and their interpretation of the period was multifaceted; tragedy was the most popular literary genres. In Chapter III, the author examines the body of works discussing Dmitry and the Time of Troubles in the 1820s and 1830s: Alexander Pushkin’s Comedy about Tsar Boris and Grishka Otrepev, Faddey Bulgarin’s Dmitry the Pretender, Alexey Khomyakov’s Dmitry the Pretender, Mikhail Pogodin’s Historical Portrait of Dmitry the Pretender. She states that the writers of Russia’s early nineteenth century were fascinated with the Dmitry materials, and each writer depicted him as a man who lived among others and saw him as an alternative to the reigning autocracy. However, they later arrived at the conclusion that there was no viable alternative to the reigning autocracy. Chapter IV deals with two plays written in response to the Era of Great Reforms in 1866: Alexander Ostrovsky’s Dmitry the Pretender and Vasily Shuisky and Nikolay Chaev’s Dmitry the Pretender. She criticizes both authors’ works on a number of fronts, regarding all of them as being overly ambitious in that they attempt to treat too many unrelated issues, and that the miscellaneous political issues raised in these dramatic works have no clear connection to one another. In the Chapter V, the author states that Dmitry disappears from Russian novels and plays for a century and reappears after the demise of the Soviet Union. She examines Daniil Mordovtsev’s False Dmitry: A Historical Novel of the Time of Troubles, Vasily Avenarius’s In Service to the Tsarevich, Nikolay Alekseev’s The False Tsarevich and Alexey Suvorin’s Tsar Dmitry the Pretender and Tsarevna Xenya. The author concludes that each writer has presented his own interpretation of Dmitry and his era, that these works are clearly independent and any similarities among them are merely coincidental with no pattern to them. Since each writer has selected his own particular assortment of “facts”, the novels each follow their own unique line of development. On a more general note, the author argues that the collection of late nineteenth century works on the Time of Troubles should be interpreted in the context of both their local frame of reference and national pride in the country’s cultural heritage. However, in the Soviet period Dmitry’s disappearance was the result of the Soviets’ emphasis on shaping the nation’s future rather than linking present realities to the national past. In the Conclusion, the author points out that all of the works discussed simultaneously deal with two distinct periods in time – the time in which the works are set and the time in which they were composed. For seventeenth century writers, marking the passing of the old dynasty was important, but the establishment of a new dynasty was just as significant. In the two eighteenth century works that were examined, contemporary political issues were treated in the context of Dmitry’s era. Nineteenth century works more closely resemble seventeenth century works in that the contemporary relevance of the historical events these works deal with is their main focus. According to the author, as long as writers continue to deal with political issues in literature or the theater, the figure of Dmitry will remain a relevant character. This book is very well written source examining the Time of Troubles period, a period when there was no legal heir to run the state, when dynastic struggle began the process of bringing an end to the Rurik Dynasty and leading to a period pretenders. The author provides different interpretations for the “protagonist”, Dmitry, within the context of Russian literature. The author particularly examines different writers’ works in chronological order and discusses the legitimacy of Dmitry by comparing the treatments of the pretenders. This book should be of interest to anyone interested in the period of the Time of Troubles and usurpation and their interpretation in Russian literature

    Trust and control in counterpoint: a case study of conductorless orchestras

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    Can a large organization be successful without a single leader? Common wisdom suggests that organizations need a leader to control and be ultimately responsible for decision-making and guarding against inefficiency and vulnerability to the behavior of employees. Nonetheless, my case study of two large conductorless orchestras -- Persimfans and Orpheus -- suggests otherwise. Such apparently leaderless organizations reject the idea of hierarchical control because it violates their fundamental goals of artistic freedom and creativity. Yet the absence of a single leader does not mean that conductorless orchestras are, in fact, leaderless. More so than conventional orchestras, they benefit from the talent, commitment, and professionalism of all their members. In contrast to rigid hierarchical control, both Persimfans and Orpheus rely extensively on trust-based governance mechanisms that are essential for collaborative decision-making. Nonetheless, they have also developed a number of less formal control strategies that facilitate the search for consensus and help create and maintain trustworthy relationships among musicians. Reliance on trust and less formal control mechanisms, however, blurs the line between these two governance strategies. To use a musical analogy, trust and control in conductorless orchestras create counterpoint, or the combination of different melodies into a more beautiful polyphonic whole. Besides offering insights into intra-organizational trust and control, my research also contributes to the literature on post-bureaucratic organizations, leadership, power, and collaboration.Ph.D.Includes bibliographical references (p. 207-224)by Dmitry Khodyako

    Negative transcriptional control of biotin metabolism genes by the TetR-type regulator BioQ in biotin-auxotrophic Corynebacterium glutamicum ATCC 13032

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    Brune I, Götker S, Schneider J, Rodionov DA, Tauch A. Negative transcriptional control of biotin metabolism genes by the TetR-type regulator BioQ in biotin-auxotrophic Corynebacterium glutamicum ATCC 13032. Journal of Biotechnology. 2011;159(3):225-234

    Identification of Genes Encoding the Folate- and Thiamine-Binding Membrane Proteins in Firmicutes

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    Genes encoding high-affinity folate- and thiamine-binding proteins (FolT, ThiT) were identified in the Lactobacillus casei genome, expressed in Lactococcus lactis, and functionally characterized. Similar genes occur in many Firmicutes, sometimes next to folate or thiamine salvage genes. Most thiT genes are preceded by a thiamine riboswitch.
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