WorldWideScience

Sample records for human disease james

  1. Doctors, disease and James Joyce.

    Science.gov (United States)

    Kaplan, Robert M

    2008-08-01

    The Irish author James Joyce is regarded as the greatest modernist writer of his time. His works, notably The Dead, A Portrait of the Artist as a Young Man, Ulysses and Finnegans Wake--are intensely autobiographic including meticulous descriptions of illness and states of health--no surprise in view of Joyce's medical history and hypochondria. The Dead revolves around the tragic love of a doomed tubercular youth. Ulysses has a graphic description of Mary Joyce-s death, a funeral and a birth; Stephen Dedalus, the character based on Joyce, attends a drinking session with medical students at the lying-in hospital just as Joyce had done as a student; references to syphilis, alcoholism and other illnesses abound.

  2. The hunters of humanity: creatures of horror in M. R. James's ghost stories

    OpenAIRE

    Oryshchuk, Nataliya

    2017-01-01

    In his ghost stories, M.R. James disclosed the most irrational and fearful aspects of archaic demonology still haunting the modern world. He turns humans into prey species, hunted and haunted by repulsive insect- and spider-like demons. This paper offers a closer look at the creatures of horror and the recurrent theme of the hunt in James's ghost stories, viewing them in the context of Victorian evolutionary theories as well as traditional medieval beliefs. James's protagonists, unimaginative...

  3. What James Parkinson Really Thought was Behind Parkinson's Disease

    OpenAIRE

    Dr. Lawrence Broxmeyer, MD

    2017-01-01

    In May, 2017, a Norwegian study done by Berstad and Berstad threw its support behind revitalizing of the hypothesis that with regard to Parkinson's disease (PD), the preponderance of convincing evidence points to a chronic infectious cause – not viral and most likely of the family Actinomycetales of which tuberculosis and the mycobacteria are premier members. The Berstads concluded that in accordance with such thoughts and despite the diagnostic challenges ahead, that further studies in human...

  4. Sir James Paget: Paget's disease of the nipple, Paget's disease of bone.

    Science.gov (United States)

    Ellis, Harold

    2013-04-01

    Sir James Paget was one of the 'great' Victorians. Eminent as a surgeon, pathologist and teacher, his nobility of character and application to his work made him a leader in his profession in that age of great men.

  5. Interpreting "Mind-Cure": William James and the "chief task…of the science of human nature".

    Science.gov (United States)

    Sutton, Emma Kate

    2012-01-01

    The private papers of the philosopher-psychologist, William James, indicate that he frequented several mental healers during his life, undertaking 100-200 therapeutic sessions concerning a range of symptoms from angina to insomnia. The success of the mind-cure movement constituted for James both a corroboration, and an extension, of the new research into the subconscious self and the psychogenesis of disease. Epistemologically, the experiences of those converts to the "mind-cure religion" exemplified his conviction that positivistic scientific enquiry can only reveal only one part of a wider reality. Metaphysically their reports comprised a powerful body of support for the existence of a "higher consciousness," a supernatural world of some description. The positing of such a source of "supernormal" healing power was, for James, the best way to reconcile the accounts of those who had been regenerated, via their faith, despite having exhausted all natural reserves of energy and will. © 2012 Wiley Periodicals, Inc.

  6. Medicine in the age of " Ulysses ": James Joyce's portrait of life, medicine, and disease on a Dublin day a century ago.

    Science.gov (United States)

    Shanahan, Fergus; Quigley, Eamonn M

    2006-01-01

    Over time, contemporary writing becomes part of the historical record. In medicine, it is an important learning tool, particularly for understanding the experience and context of disease and illness. Although a century has elapsed since the fictional events on a single day described in James Joyce's Ulysses, the work is still fresh with references and allusions to doctors, illnesses, and the human experience. Ulysses provides perspective on medical and social history and offers a biting commentary of continuing relevance to the doctor-patient relationship.

  7. The medical treatment of Parkinson disease from James Parkinson to George Cotzias.

    Science.gov (United States)

    Fahn, Stanley

    2015-01-01

    It took exactly 150 years since James Parkinson's description in 1817 of the illness bearing his name until the development of effective therapy for this disorder, namely, the introduction of high-dosage levodopa by George Cotzias in 1967. During the first 50 years, no effective therapy was available, but neurologists reported using different agents, including metals. Then, around 1867, Charcot found solanaceous alkaloids to be somewhat helpful, and these became the accepted and popular therapy for the next 75 years. When basic scientists discovered that these alkaloids had central antimuscarinic activity, pharmaceutical chemists developed synthetic chemical agents that were equally effective, with possibly less adverse effects, and around 1950 these synthetic drugs became the standard medical therapy for Parkinson's disease (PD). The link between dopamine and PD did not take place until 1957, 140 years after Parkinson's Essay. The clue came from research on reserpine, a drug derived from the Rauwolfia plant that caused a sedative effect, now recognized as a drug-induced parkinsonian state. Initial investigations revealed that reserpine caused the release and depletion of serotonin stores in the brain. With that knowledge, Arvid Carlsson, a young pharmacologist in Sweden, decided to explore the possibility that reserpine might also affect brain catecholamines. In his now famous, elegant, and simple experiment, he showed that injecting l-dopa, the precursor of catecholamines, alleviated the reserpine-induced parkinsonian state in animals, whereas the precursor of serotonin failed to do so. Carlsson then developed a highly sensitive assay to measure dopamine, and his lab found that dopamine is selectively present in high concentrations in the striatum and that administered l-dopa could restore the dopamine depleted by reserpine. Carlsson postulated that all these findings implicate dopamine in motor disorders. Oleh Hornykiewicz, a young pharmacologist in Vienna, on

  8. James Gillies

    CERN Multimedia

    2008-01-01

    "Physicist James gillies is chief of communications at CERN (the European Organisation for Nuclear Research). Based in the Jura foothills, just outside Geneva, Gillies is part of a teamt hat will fire up CERN's Large Hadron Collierd (LHC) - the most complicated piece of scientific equipment ever built." (1/2 page)

  9. Totally James

    Science.gov (United States)

    Owens, Tom

    2006-01-01

    This article presents an interview with James Howe, author of "The Misfits" and "Totally Joe". In this interview, Howe discusses tolerance, diversity and the parallels between his own life and his literature. Howe's four books in addition to "The Misfits" and "Totally Joe" and his list of recommended books with lesbian, gay, bisexual, transgender,…

  10. From Performance to Decision Processes in 33 Years: A History of Organizational Behavior and Human Decision Processes under James C. Naylor.

    Science.gov (United States)

    Weber

    1998-12-01

    For the past 33 years, Organizational Behavior and Human Decision Processes has thrived under a single editor. That editor, James C. Naylor, is retiring from his long stewardship. This article chronicles the course of the journal under Jim's direction and marks some of the accomplishments and changes over the past three decades that go to his credit. Copyright 1998 Academic Press.

  11. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...

  12. James Craufurd Gregory, 19th century Scottish physicians, and the link between occupation as a coal miner and lung disease.

    Science.gov (United States)

    Donaldson, K; Wallace, W A; Elliot, T A; Henry, C

    2017-09-01

    By the mid-19th century about 200,000 miners were employed in a UK coal mining industry still growing with the advances of the Industrial Revolution. Coal miners were long known to suffer poor health but the link to inhaling dust in the mines had not been made. In 1813 George Pearson was the first to suggest that darkening of lungs seen in normal individuals as they aged was caused by inhaled soot from burning oil, candles and coal, which were the common domestic sources of heat and light. In 1831 Dr James Craufurd Gregory first described black pigmentation and disease in the lungs of a deceased coal miner and linked this to pulmonary accumulation of coal mine dust. Gregory hypothesised that the black material seen at autopsy in the collier's lungs was inhaled coal dust and this was confirmed by chemical analysis carried out by Professor Sir Robert Christison. Gregory suggested that coal dust was the cause of the disease and warned physicians in mining areas to be vigilant for the disease. This first description of what came to be known as 'coal worker's pneumoconiosis' sparked a remarkable intellectual effort by physicians in Scotland, culminating in a large body of published work that led to the first understandings of this disease and its link to coalblackened lungs. This paper sets out the history of the role of Scottish physicians in gaining this understanding of coal worker's pneumoconiosis. It describes Gregory's case and the lung - recently discovered in the pathology collection of the Surgeons' Hall Museums, Edinburgh, where it has lain unnoticed for over 180 years - on which Gregory based his landmark paper.

  13. James B. Macdonald: A Bibliography.

    Science.gov (United States)

    Brubaker, Dale L., Comp.; Brookbank, Gayle, Comp.

    1986-01-01

    Presents a bibliography of James B. Macdonald's writings and printed speeches arranged chronologically according to the educator's themes of inquiry. Macdonald's videotaped autobiography identifies four explorative stages: (1) Scientism, (2) person-centered humanism, (3) sociopolitical humanism, and (4) transcendentalism, signaling a need for…

  14. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  15. Linking Microbiota to Human Diseases

    DEFF Research Database (Denmark)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, F

    2015-01-01

    The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2...

  16. in Human Liver Diseases

    Directory of Open Access Journals (Sweden)

    Minoru Fujimoto

    2010-01-01

    Full Text Available Toll-like receptor (TLR signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases.

  17. Human radiation studies: Remembering the early years: Oral history of physician James S. Robertson, M.D., Ph.D., conducted January 20, 1995

    International Nuclear Information System (INIS)

    1995-09-01

    This report is a transcript of in interview of Dr. James S. Robertson by representatives of the DOE Office of Human Radiation Experiments. Dr. Robertson was chosen for this interview because of his research at Brookhaven National Laboratory, especially on Boron Neutron Capture Therapy (BNCT); his work at the United States Naval Defense Laboratory; and his work at the Atomic Energy Commission. After a brief biographical sketch Dr. Robertson discusses research on human subjects at Berkeley, his contributions to the beginnings of Neutron Capture Therapy at Brookhaven, his participation with the Brookhaven Human Use Committee, his involvement in the study of the effects of Castle Bravo event on the Marshallese, and his work with the Naval Radiological Defense Laboratory

  18. Human radiation studies: Remembering the early years: Oral history of physician James S. Robertson, M.D., Ph.D., conducted January 20, 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    This report is a transcript of in interview of Dr. James S. Robertson by representatives of the DOE Office of Human Radiation Experiments. Dr. Robertson was chosen for this interview because of his research at Brookhaven National Laboratory, especially on Boron Neutron Capture Therapy (BNCT); his work at the United States Naval Defense Laboratory; and his work at the Atomic Energy Commission. After a brief biographical sketch Dr. Robertson discusses research on human subjects at Berkeley, his contributions to the beginnings of Neutron Capture Therapy at Brookhaven, his participation with the Brookhaven Human Use Committee, his involvement in the study of the effects of Castle Bravo event on the Marshallese, and his work with the Naval Radiological Defense Laboratory.

  19. Temporal modulation visual fields, normal aging, Parkinson's disease and methyl-mercury in the James Bay Cree: a feasibility study

    Directory of Open Access Journals (Sweden)

    Jocelyn Faubert

    2003-01-01

    Full Text Available We assessed temporal modulation visual fields (TMFs for 91 observers including controls, Parkinson patients and members of the James Bay Cree community of Northern Québec suspected of being chronically exposed to relatively low levels of methyl-mercury. The main goal was to establish the feasibility of using such procedures to rapidly evaluate visual function in a large field study with the James Bay Cree community. The results show clear normal aging effects on TMFs and the pattern of loss differed depending on the flicker rates used. Group data comparisons between the controls and the experimental groups showed significant effects only between the Cree and normal controls in the 40 to 49 year-old age category for the low temporal frequency condition (2 Hz. Examples of individual analysis shows a Cree observer with severe visual field constriction at the 2 Hz condition with a normal visual field at the 16 Hz condition and a reverse pattern was demonstrated for a Parkinson's patient where a visual field constriction was evident only for the 16 Hz condition. The general conclusions are: Such a technique can be used to evaluate the visual consequences of neuropathological disorders and it may lead to dissociation between certain neurotoxic and neurodegenerative effects depending on the parameters used; this technique can be used for a large field study because it is rapid and easily understood and performed by the subjects; the TMF procedure used showed good test-retest correlations; normal aging causes changes in TMF profiles but the changes will show different patterns throughout the visual field depending on the parameters used.

  20. What are the dietary treatment research priorities for inflammatory bowel disease? A short report based on a priority setting partnership with the James Lind Alliance.

    Science.gov (United States)

    Lomer, M C; Hart, A L; Verjee, A; Daly, A; Solomon, J; Mclaughlin, J

    2017-12-01

    Treatment of inflammatory bowel disease (IBD) involves a multidisciplinary approach comprising medical management and sometimes surgery. Although diet is central to IBD management, the optimal diet for patients with IBD is uncertain. A UK collaborative partnership within the James Lind Alliance was set up between patients, clinicians and other stakeholders to develop research priorities in IBD. The aim of this short report is to provide a comprehensive summary of the research priority findings relating to diet in the treatment of IBD. The James Lind Alliance Priority Setting Partnership process was used to develop research priorities in IBD. In brief, patients, clinicians and other stakeholders were invited to provide up to five treatment uncertainties in IBD. These uncertainties were collated, revised and ranked, leading to a final top 10 research questions in IBD. A total of 1671 uncertainties from 531 participants were collected and refined to exclude duplicates leaving 1253 uncertainties. Of these, 348 were categorised as diet-related and grouped according to topic. There were 206 uncertainties related to how diet can be used to treat IBD or alleviate symptoms. Seventy-two percent of diet-related questions came from patients. One broadly diet-related and two diet-specific treatment uncertainties were included in the top 10 research priorities for IBD. Dietary treatment options in the management of IBD are important research priorities. Almost three-quarters of diet related questions came from patients, who were particularly interested in how diet can impact disease activity and symptom control. © 2017 The British Dietetic Association Ltd.

  1. Influenza as a human disease

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Influenza as a human disease. Commonly perceived as a mild disease, affects every one, sometimes a couple of times in a year. Globally, seasonal influenza epidemics result in about three to five million yearly cases of severe illness and about 250,000 to 500,000 yearly ...

  2. Human communicable diseases

    International Nuclear Information System (INIS)

    2003-01-01

    The rising incidence of malaria and tuberculosis in sub-Saharan Africa is causing great hardship, not only to the individuals affected but also to the economies of the countries where they are rife. Both diseases are becoming more resistant to the drugs that are currently available for treatment and drug resistant strains are posing a global threat. The International Atomic Energy Agency (IAEA) is responding by sponsoring a programme to build technical competency in molecular and radioisotope-based techniques. (IAEA)

  3. James Watt's Leicester Walk

    OpenAIRE

    Bell, Kathleen

    2016-01-01

    a poem in which James Watt, inventor of the separate condenser, walks through contemporary Leicester (his route is from Bonners Lane and alongside the canal, taking in the Statue of Liberty on its traffic island near Sage Road). It is derived from the exercise of taking a character for a walk,

  4. How James Wood Works

    Science.gov (United States)

    Goldstein, Evan R., Comp.

    2008-01-01

    Reading through news-media clippings about James Wood, one might reasonably conclude that "pre-eminent critic" is his official job title. In fact, Wood is a staff writer for "The New Yorker" and a professor of the practice of literary criticism at Harvard University. But at a time when there is much hand-wringing about the death of the…

  5. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  6. Cohesin and Human Disease

    Science.gov (United States)

    Liu, Jinglan; Krantz, Ian D.

    2016-01-01

    Cornelia de Lange syndrome (CdLS) is a dominant multisystem disorder caused by a disruption of cohesin function. The cohesin ring complex is composed of four protein subunits and more than 25 additional proteins involved in its regulation. The discovery that this complex also has a fundamental role in long-range regulation of transcription in Drosophila has shed light on the mechanism likely responsible for its role in development. In addition to the three cohesin proteins involved in CdLS, a second multisystem, recessively inherited, developmental disorder, Roberts-SC phocomelia, is caused by mutations in another regulator of the cohesin complex, ESCO2. Here we review the phenotypes of these disorders, collectively termed cohesinopathies, as well as the mechanism by which cohesin disruption likely causes these diseases. PMID:18767966

  7. Proteins aggregation and human diseases

    Science.gov (United States)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  8. Entrevista a James Curran

    OpenAIRE

    Curran, James; Figueiras, Rita; Ribeiro, Nelson

    2012-01-01

    James Curran é professor catedrático e diretor do Goldsmiths Leverhulme Media Research Centre. A sua investigação centra-se sobretudo na relação entre os media e a democracia, quer através do ângulo da história dos media, quer da economia política dos media, áreas sobre as quais publicou mais de duas dezenas de livros, como Media and Democracy, Power without Responsability (co-autoria de Jean Seaton) e Media and Society. Na sua obra mais recente, Misunderstanding the Internet (co-autoria de N...

  9. Transfer RNA and human disease

    Directory of Open Access Journals (Sweden)

    Jamie A Abbott

    2014-06-01

    Full Text Available Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA genes are hotspots for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase, mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing. Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  10. Transfer RNA and human disease.

    Science.gov (United States)

    Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

    2014-01-01

    Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  11. Proteins aggregation and human diseases

    International Nuclear Information System (INIS)

    Hu, Chin-Kun

    2015-01-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease. (paper)

  12. An interview with James Briscoe.

    Science.gov (United States)

    Brown, Katherine

    2018-03-27

    James Briscoe is a group leader at The Francis Crick Institute in London. His lab's research focusses on the developing vertebrate spinal cord, with a particular interest in how sonic hedgehog gradients, and the downstream signal transduction and transcriptional networks, regulate the development of this tissue. In September 2018, James will become the new Editor-in-Chief of Development. We met with James to discuss his career and research interests, the importance of interdisciplinary thinking in developmental biology, and his views on the current state and future opportunities in scientific publishing. © 2018. Published by The Company of Biologists Ltd.

  13. Quantitative genetics of disease traits.

    Science.gov (United States)

    Wray, N R; Visscher, P M

    2015-04-01

    John James authored two key papers on the theory of risk to relatives for binary disease traits and the relationship between parameters on the observed binary scale and an unobserved scale of liability (James Annals of Human Genetics, 1971; 35: 47; Reich, James and Morris Annals of Human Genetics, 1972; 36: 163). These two papers are John James' most cited papers (198 and 328 citations, November 2014). They have been influential in human genetics and have recently gained renewed popularity because of their relevance to the estimation of quantitative genetics parameters for disease traits using SNP data. In this review, we summarize the two early papers and put them into context. We show recent extensions of the theory for ascertained case-control data and review recent applications in human genetics. © 2015 Blackwell Verlag GmbH.

  14. Tight junctions and human diseases.

    Science.gov (United States)

    Sawada, Norimasa; Murata, Masaki; Kikuchi, Keisuke; Osanai, Makoto; Tobioka, Hirotoshi; Kojima, Takashi; Chiba, Hideki

    2003-09-01

    Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

  15. James Blunt matuselaulude edetabeli tipus

    Index Scriptorium Estoniae

    2006-01-01

    Bereavement Registeri andmetel Suurbritannias matustel tellitavate laulude edetabelis: James Blunt "Goodbye My Lover", Robbie Williams "Angels", Jennifer Warnes ja Bill Medley "I've Had the Time Of My Life", Elton John "Candle in the Wind", Righteous Brothers "Unchained Melody"

  16. Social and environmental impacts of the James Bay hydroelectric project

    International Nuclear Information System (INIS)

    Hornig, J.F.

    1999-01-01

    The book, which is an analysis and not an advocacy, examines the anatomy of the controversy that has swirled around the James Bay project - the La Grande and Great Whale projects combined - from the 1970s to the 1990s, and seeks, in the process, to determine whether there are lessons that can be learned from such an analysis that are applicable to other cases as well as to James Bay itself. The contributors are interested, at one and the same time, in finding ways to integrate the knowledge of natural scientists and social scientists to deepen the understanding of human/environment relations and to link science and policy to encourage a productive dialogue between practitioners and scholars in this increasingly important area of inquiry. The contributor's papers include the following: introduction to the issues; hydroelectric power development at James Bay: establishing a frame of reference; James Bay: environmental considerations for building large hydroelectric dams and reservoirs in Quebec; elevated mercury in fish as a result of the James Bay hydroelectric power development: perception and reality; the Cree people of James Bay: assessing the social impacts of hydroelectric dams and reservoirs; culture, social change, and Cree opposition to the James Bay hydroelectric development; and the impact of James Bay hydroelectric development on the art and craft of the James Bay Cree. The authors of the volume have attempted to stand back and examine just a few of these issues from the perspective of a variety of disciplines, and their purpose is to inform and stimulate thoughtful consideration by providing an overall perspective that might might serve to broaden the context in which specific issues can be debated. refs., 3 tabs., 5 figs

  17. Successful pregnancy outcome in Swyer-James-Macleod syndrome

    Directory of Open Access Journals (Sweden)

    Chopra Seema

    2008-01-01

    Full Text Available Swyer-James-MacLeod (SJM syndrome is a chronic, progressive lung disease as a result of infection and bronchial obstruction that ultimately leads to emphysema. It is associated with chronic cough, sputum production and recurrent chest infections and is occasionally seen in women of reproductive age. The radiological finding of unilateral hyperlucent lung is considered synonymous with the disease entity.

  18. James Stevens / James Stevens ; interv. Tilman Baumgärtel

    Index Scriptorium Estoniae

    Stevens, James

    2006-01-01

    Inglise disainerist James Stevensist (sünd. 1962) ja tema tegevusest. J. Stevens 2000. a. Amsterdamis tehtud intervjuus koos Jon Bainsi ja Kim Bulliga 1995. a. Londonis avatud Interneti-agentuurist Obsolete, 1996-2000 tegutsenud Interneti-kohvikust Backspace, mittekommertsiaalse juhtmeteta nerworki Consume.net rajamisest Londonis

  19. James Moir as Organic Chemist

    African Journals Online (AJOL)

    NICO

    James Moir (1874–1929) played an important role in the field of chemistry in South ... into the colour of organic compounds and the relationship be- tween colour ...... theory put forward by E.R.Watson,34 the depth of colour, or the displacement .... cover-glass, such as used in microscopy, to photograph absorp- tion bands ...

  20. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.

  1. Roentgenosemiotics and diagnosis of human diseases

    International Nuclear Information System (INIS)

    Mikhajlov, A.N.

    1989-01-01

    Modern concepts concerning roentgenologic semiotics, diagnosis of almost all the human diseases as well as the features of roentgenologic examintion of organs and systems are described. Roentgenologic symptoms and syndroms are systematized and standardized by anatomy branches. 48 refs

  2. Protein Misfolding and Human Disease

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter Gerd; Vang, Søren

    2006-01-01

    phenylketonuria, Parkinson's disease, α-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute...

  3. Annotating the human genome with Disease Ontology

    Science.gov (United States)

    Osborne, John D; Flatow, Jared; Holko, Michelle; Lin, Simon M; Kibbe, Warren A; Zhu, Lihua (Julie); Danila, Maria I; Feng, Gang; Chisholm, Rex L

    2009-01-01

    Background The human genome has been extensively annotated with Gene Ontology for biological functions, but minimally computationally annotated for diseases. Results We used the Unified Medical Language System (UMLS) MetaMap Transfer tool (MMTx) to discover gene-disease relationships from the GeneRIF database. We utilized a comprehensive subset of UMLS, which is disease-focused and structured as a directed acyclic graph (the Disease Ontology), to filter and interpret results from MMTx. The results were validated against the Homayouni gene collection using recall and precision measurements. We compared our results with the widely used Online Mendelian Inheritance in Man (OMIM) annotations. Conclusion The validation data set suggests a 91% recall rate and 97% precision rate of disease annotation using GeneRIF, in contrast with a 22% recall and 98% precision using OMIM. Our thesaurus-based approach allows for comparisons to be made between disease containing databases and allows for increased accuracy in disease identification through synonym matching. The much higher recall rate of our approach demonstrates that annotating human genome with Disease Ontology and GeneRIF for diseases dramatically increases the coverage of the disease annotation of human genome. PMID:19594883

  4. Physiochemical basis of human degenerative disease.

    Science.gov (United States)

    Zeliger, Harold I; Lipinski, Boguslaw

    2015-03-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  5. Physiochemical basis of human degenerative disease

    Directory of Open Access Journals (Sweden)

    Zeliger Harold I.

    2015-03-01

    Full Text Available The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  6. Human diseases associated with defective DNA repair

    International Nuclear Information System (INIS)

    Friedberg, E.C.; Ehmann, U.K.; Williams, J.I.

    1979-01-01

    The observations on xeroderma pigmentosum (XP) cells in culture were the first indications of defective DNA repair in association with human disease. Since then, a wealth of information on DNA repair in XP, and to a lesser extent in other diseases, has accumulated in the literature. Rather than clarifying the understanding of DNA repair mechanisms in normal cells and of defective DNA repair in human disease, the literature suggests an extraordinary complexity of both of the phenomena. In this review a number of discrete human diseases are considered separately. An attempt was made to systematically describe the pertinent clinical features and cellular and biochemical defects in these diseases, with an emphasis on defects in DNA metabolism, particularly DNA repair. Wherever possible observations have been correlated and unifying hypotheses presented concerning the nature of the basic defect(s) in these diseases. Discussions of the following diseases are presented: XP, ataxia telangiectasia; Fanconi's anemia; Hutchinson-Gilford progeria syndrome; Bloom's syndrome, Cockayne's syndrome; Down's syndrome; retinoblastoma; chronic lymphocytic leukemia; and other miscellaneous human diseases with possble DNA repair defects

  7. Molecular Pathology of Human Prion Diseases

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.

  8. Global biogeography of human infectious diseases.

    Science.gov (United States)

    Murray, Kris A; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R; Daszak, Peter

    2015-10-13

    The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non-vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and "Wallacean" zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.

  9. Melatonin and human mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    Reza Sharafati-Chaleshtori

    2017-01-01

    Full Text Available Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.

  10. Plebotomine Vectors of Human Disease.

    Science.gov (United States)

    1984-12-30

    incriminated as vectors of Leishmania mexicana among rodents and/or humans from Mexico to the Amazon Basin. Specimens referable to L. olmeca olmeca...in the format similar to that given for the species group baityi included in this report. Additional phlebotomines from Tanzania, Brazil, Peru and...species group baityi included in this report. Additional phlebotomines from Tanzania, Brazil, Peru and Venezuela were slide-mounted and added to the

  11. Genomic uracil and human disease

    DEFF Research Database (Denmark)

    Hagen, Lars; Pena Diaz, Javier; Kavli, Bodil

    2006-01-01

    Uracil is present in small amounts in DNA due to spontaneous deamination of cytosine and incorporation of dUMP during replication. While deamination generates mutagenic U:G mismatches, incorporated dUMP results in U:A pairs that are not directly mutagenic, but may be cytotoxic. In most cells, mut...... retroviral infections. Ung(-/-) mice have a similar phenotype and develop B-cell lymphomas late in life. However, there is no evidence indicating that UNG deficiency causes lymphomas in humans....

  12. Sustainable development in the Hudson Bay/James Bay bioregion

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    An overview is presented of projects planned for the James Bay/Hudson Bay region, and the expected environmental impacts of these projects. The watershed of James Bay and Hudson Bay covers well over one third of Canada, from southern Alberta to central Ontario to Baffin Island, as well as parts of north Dakota and Minnesota in the U.S.A. Hydroelectric power developments that change the timing and rate of flow of fresh water may cause changes in the nature and duration of ice cover, habitats of marine mammals, fish and migratory birds, currents into and out of Hudson Bay/James Bay, seasonal and annual loads of sediments and nutrients to marine ecosystems, and anadromous fish populations. Hydroelectric projects are proposed for the region by Quebec, Ontario and Manitoba. In January 1992, the Canadian Arctic Resources Committee (CARC), the Environmental Committee of Sanikuluaq, and the Rawson Academy of Arctic Science will launch the Hudson Bay/James Bay Bioregion Program, an independent initiative to apply an ecosystem approach to the region. Two main objectives are to provide a comprehensive assessment of the cumulative impacts of human activities on the marine and freshwater ecosystems of the Hudson Bay/James Bay bioregion, and to foster sustainable development by examining and proposing cooperative processes for decision making among governments, developers, aboriginal peoples and other stakeholders. 1 fig

  13. James Madison's Practical Ideals for the 1990s.

    Science.gov (United States)

    Delattre, Edwin J.

    This paper examines recent behavior of public officials at various levels of government in the United States, finds a systemic failure to meet ethical standards, and concludes that the wisdom of James Madison has much applicability to current times. Given his keen perception of human nature, Madison would not be too surprised at today's poor…

  14. James Peacock, Understanding Paul Auster

    Directory of Open Access Journals (Sweden)

    Chrysavgi Papayianni

    2011-10-01

    Full Text Available Paul Auster’s impressive gamut of work continues to incite fascination and controversy. Indeed, his compelling storytelling style taken together with his mixing of crime fiction and absurdism has made his readers and critics vacillate between praise and condemnation. James Peacock’s Understanding Paul Auster, sheds new light to otherwise obscure aspects of Auster’s novels, films, and other works undermining in this way the negative criticism of the past and thus creating a new appreciation fo...

  15. Conference James F.Buckli

    CERN Multimedia

    Buckli,J

    1988-01-01

    L'association du personnel a le plaisir d'accueillir Mons. James F.Buckli, astronaute, né en 1947. Il a participé à la mission Space Lab D1 qui pour la première fois mettait 8 personnes sur orbite.L'ass.du pers. remercie aussi Gordon White(s) de la mission américaine d'avoir permis d'organiser cette conférence

  16. A Conversation with James Hannan

    OpenAIRE

    Gilliland, Dennis; Ramamoorthi, R. V.

    2010-01-01

    Jim Hannan is a professor who has lived an interesting life and one whose fundamental research in repeated games was not fully appreciated until late in his career. During his service as a meteorologist in the Army in World War II, Jim played poker and made weather forecasts. It is curious that his later research included strategies for repeated play that apply to selecting the best forecaster. ¶ James Hannan was born in Holyoke, Massachusetts on September 14, 1922. He attended St. Jero...

  17. Obituary: James Houck (1940 - 2015)

    Science.gov (United States)

    Weedman, Daniel; Barry, Donald; Soifer, Thomas

    James R. Houck, the leading figure in developing infrared spectroscopy for astrophysics, died in Ithaca, NY, on September 18, 2015, at age 74 from complications of Alzheimer's Disease. He was born on October 5, 1940, in Mobile, Alabama, but lived much of his early life in Pittsburgh, Pennsylvania, where he received his undergraduate degree from Carnegie Institute of Technology. Jim spent his scientific career at Cornell University. He came to Cornell as a physics graduate student in 1962 and remained until his retirement as the Kenneth A. Wallace Professor of Astronomy in 2012. His only year away from Ithaca was as a Guggenheim Fellow at Caltech, and he declined job offers from other universities because of his opinion that Ithaca provided the best environment for raising his family. His passion for learning, doing, and teaching science by building instruments and understanding physics led to great benefits for his students and astronomy colleagues. After receiving his PhD in condensed matter physics, he changed fields to work in astronomy at Cornell. He first collaborated with colleague Martin Harwit to develop a rocket program at Cornell for infrared observations and made numerous treks to the White Sands Missile Range flying payloads on Aerobee sounding rockets. Jim emphasized building spectrographs and making pioneering observations with ground based, airborne, and rocket-borne infrared instrumentation. Jim flew on every airplane NASA provided for astronomy. Those were pioneering times. One of his survival stories was of the Learjet in which both engines flamed out over the Pacific when the pilot did a celebratory barrel role after successful completion of their observations. His observations with rockets and airplanes were primarily of a variety of Galactic objects, including planetary nebulae, HII regions, and stars. But the most notable was an observation on the Convair 990 that produced a prescient discovery paper in 1973 led by Jim which discovered bound

  18. Intervjuu James Corneriga = Interview with James Corner / James Corner ; interv. Andres Sevtshuk

    Index Scriptorium Estoniae

    Corner, James

    2006-01-01

    Büroo Field Operations maastikuarhitekt ning Pennsylvania Ülikooli maastikuarhitektuuri osakonna juhataja James Corner oma büroost, maastikust kui "instrumendist", postindustriaalsete aladega seotud projektidest (New Yorgi High Line'i muutmine pargiks ja promenaadiks), tööst suuremahuliste maastikega (Fresh Kills'i soo, endise prügila muutmine pargialaks), maastikuarhitektuurist ja linnakujundusest (maastiku urbanism), õpetamise tähtsusest oma töös ja maastikuarhitektuuri ideede arendamisel. Bibl. lk. 24

  19. Use of human factors in the integration of a safety parameter display system (SPDS) and emergency response facility (ERF) capabilities for the James A. Fitzpatrick nuclear power plant

    International Nuclear Information System (INIS)

    Fish, H.C. Jr.; Gutierrez, R.

    1987-01-01

    In 1987, New York Power Authority's Emergency and Process Information Computer (EPIC) System will be operational. The EPIC system was designed to perform two distinct functions: to serve as an advanced replacement for the existing plant process computer and to assist in providing the JAFNPP operations staff with information during plant emergency conditions. Besides meeting the operational and regulatory goals of NYPA, EPIC was designed to meet NYPA human factors criteria. Using human factors literature, industry standards and guidelines, a Human Factors Criteria document was prepared for the EPIC project. This document served as the bases for all hardware, display, and documentation design applicable to EPIC. The major tasks of the EPIC human factors plan include integration of past and present applicable human factors information, establishment of a user definition using data gathered from control room observations (startup and shutdown of JAFNPP), survey of computer programs used by the operators, and obtaining input from licensed operators. These major tasks played a role in the design of the design of the control room configuration, the design and development of computer generated displays, and the format in which the displayed and hard copy information would be presented to the user. This paper presents an overview of the human factors work performed and the documents researched or developed in the design of EPIC displays, software, and hardware. The location and operation of this new computer based information system, like the displays was based on the systematic application of operations and human factors principles

  20. [Diseases transmitted through water for human consumption].

    Science.gov (United States)

    Franco, E; Dentamaro, M

    2003-01-01

    The water for human consumption maintains a biological risk and can transmit diseases. The classical waterborne and the presently frequent diseases caused by protozoi Giardia and Cryptosporidium are considered and Arcobacter butzleri, a new waterborne pathogen, is described. Many measures have been adopted by institutions to ensure the quality of the drinking water. Managers and public health operators is working in order to verify the efficiency of more suitable indicators for its monitoring.

  1. Modeling human disease using organotypic cultures

    DEFF Research Database (Denmark)

    Schweiger, Pawel J; Jensen, Kim B

    2016-01-01

    animal models and in vitro cell culture systems. However, it has been exceedingly difficult to model disease at the tissue level. Since recently, the gap between cell line studies and in vivo modeling has been narrowing thanks to progress in biomaterials and stem cell research. Development of reliable 3D...... culture systems has enabled a rapid expansion of sophisticated in vitro models. Here we focus on some of the latest advances and future perspectives in 3D organoids for human disease modeling....

  2. Mouse Chromosome Engineering for Modeling Human Disease

    OpenAIRE

    van der Weyden, Louise; Bradley, Allan

    2006-01-01

    Chromosomal rearrangements occur frequently in humans and can be disease-associated or phenotypically neutral. Recent technological advances have led to the discovery of copy-number changes previously undetected by cytogenetic techniques. To understand the genetic consequences of such genomic changes, these mutations need to be modeled in experimentally tractable systems. The mouse is an excellent organism for this analysis because of its biological and genetic similarity to humans, and the e...

  3. Immunotherapy of Human Papilloma Virus Induced Disease

    Science.gov (United States)

    van der Burg, Sjoerd H

    2012-01-01

    Immunotherapy is the generic name for treatment modalities aiming to reinforce the immune system against diseases in which the immune system plays a role. The design of an optimal immunotherapeutic treatment against chronic viruses and associated diseases requires a detailed understanding of the interactions between the target virus and its host, in order to define the specific strategies that may have the best chance to deliver success at each stage of disease. Recently, a first series of successes was reported for the immunotherapy of Human Papilloma Virus (HPV)-induced premalignant diseases but there is definitely room for improvement. Here I discuss a number of topics that in my opinion require more study as the answers to these questions allows us to better understand the underlying mechanisms of disease and as such to tailor treatment. PMID:23341861

  4. James Joyce, music and memory

    OpenAIRE

    Brown, Katie

    2007-01-01

    This thesis, James Joyce, Music and Memory, explores the connection between music and Irish cultural memory in Joyce’s works from Chamber Music to the “pure music” of Finnegans Wake. Overall, it shows that Joyce’s ongoing desire to emulate musical forms must be seen in light of Joyce’s wish to come to terms with Irish cultural history, as these are the driving forces that bring about his changes in style. TARA (Trinity’s Access to Research Archive) has a robust takedown policy. Please cont...

  5. Reduced penetrance in human inherited disease

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-01-31

    Jan 31, 2014 ... tant role in cellular senescence, tumorigenesis and in several diseases including type ... between epigenetic DNA modifications and human life span has also been shown .... penetrance mutation that is age dependent especially when compared with the ..... on healthy aging and longevity. Immunity Aging ...

  6. Primatology. Human diseases threaten great apes.

    Science.gov (United States)

    Ferber, D

    2000-08-25

    Researchers are uncovering disturbing evidence that scientists and tourists are infecting wild primates with human pathogens. In response, ape specialists, including the American Society of Primatologists, are now calling for stricter health standards for researchers and tourists. They are also urging researchers to learn how to diagnose disease in their study animals.

  7. Emerging arboviral human diseases in Southern Europe.

    Science.gov (United States)

    Papa, Anna

    2017-08-01

    Southern Europe is characterized by unique landscape and climate which attract tourists, but also arthropod vectors, some of them carrying pathogens. Among several arboviral diseases that emerged in the region during the last decade, West Nile fever accounted for high number of human cases and fatalities, while Crimean-Congo hemorrhagic fever expanded its geographic distribution, and is considered as a real threat for Europe. Viruses evolve rapidly and acquire mutations making themselves stronger and naive populations more vulnerable. In an effort to tackle efficiently the emerging arboviral diseases, preparedness and strategic surveillance are needed for the early detection of the pathogen and containment and mitigation of probable outbreaks. In this review, the main human arboviral diseases that emerged in Southern Europe are described. © 2017 Wiley Periodicals, Inc.

  8. Physiology as the antechamber to metaphysics: the young William James's hope for a philosophical psychology.

    Science.gov (United States)

    Croce, P J

    1999-11-01

    In the 5 years before 1878, when his career in psychology was becoming established, William James wrote a series of notes and reviews assessing the work of many of the pioneers in the new field. Adopting a public and confident voice, even while he was privately still uncertain and searching, James criticized the dogmatism of positivist and idealist claims to the study of the human brain and mind. In his short writings of 1873-1877, James started to formulate his own middle path. His first steps on that path show that he did not reject either scientific or philosophic inquiry; instead, he viewed scientific knowledge as a way to understand philosophical questions more deeply. Saving his sharpest critiques for positivism, James endorsed scientific investigation without materialist assmptions. While his career in psychology was still only a hope, James treated science as a means toward humanist insight.

  9. Human endogenous retroviruses in neurologic disease.

    Science.gov (United States)

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  10. Molecular biology of human muscle disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  11. The nuclear envelopathies and human diseases

    Directory of Open Access Journals (Sweden)

    Jeang Kuan-Teh

    2009-10-01

    Full Text Available Abstract The nuclear envelope (NE consists of two membrane layers that segregate the nuclear from the cytoplasmic contents. Recent progress in our understanding of nuclear-lamina associated diseases has revealed intriguing connections between the envelope components and nuclear processes. Here, we review the functions of the nuclear envelope in chromosome organization, gene expression, DNA repair and cell cycle progression, and correlate deficiencies in envelope function with human pathologies.

  12. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. The role of chemerin in human disease

    Directory of Open Access Journals (Sweden)

    Magdalena Stojek

    2017-02-01

    Full Text Available Adipose tissue is not merely a storage depot of triacylglycerols but also a major endocrine organ. Its cells, including adipocytes, synthesize and secrete a range of biologically active molecules termed adipokines. Adipokines that display the properties of cytokines are often called adipocytokines. In recent years there has been increasing interest in a new adipokine called chemerin. Chemerin is a protein synthesized mostly by the adipose tissue and the liver as inactive pre-pro-chemerin. After the intracellular hydrolytic cutting off of the 20-amino-acid N-terminal polypeptide, it is secreted into the bloodstream as inactive pro-chemerin. Biologically active chemerin is then derived from pro-chemerin after cleavage of the C-terminal fragment by serum proteases involved in inflammation, coagulation and fibrinolysis. Proteolytic cleavage leads to formation of several chemerin-derived peptides, both biologically active (often with opposing functions and inactive.Within the last decade, there has been a growing number of publications regarding the role of chemerin in human disease. It seems to be implicated in the inflammatory response, metabolic syndrome, cardiovascular disease and alimentary tract disorders. The article presents the most recent information on the role of chemerin in human disease, and specifically alimentary tract disorders. The available evidence suggests that chemerin is an important link between adipose tissue mass, metabolic processes, the immune system and inflammation, and therefore plays a major role in human pathophysiology.

  14. Environmental Assessment on the leasing of the Strategic Petroleum Reserve, St. James Terminal, St. James Parish, Louisiana

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-01-01

    The US Department of Energy (DOE) proposes to lease the Strategic Petroleum Reserve`s (SPR) St. James Terminal to private industry. The St. James Terminal consists of six storage tanks, a pumping station, two maine docks and ancillary facilities. DOE believes that the St. James Terminal presents an opportunity to establish a government- industry arrangement that could more effectively use this asset to serve the nations`s oil distribution needs, reduce the operational cost of the SPR, and provide a source of revenue for the Government. DOE solicited interest in leasing its distribution facilities in a notice published March 16, 1994. In response, industry has expressed interest in leasing the St. James Terminal, as well as several DOE pipelines, to enhance the operation of its own facilities or to avoid having to construct new ones. Under such a lease, industry use would be subordinate to DOE use in the event of a national energy emergency. This Environmental Assessment describes the proposed leasing operation, its alternatives, and potential environmental impacts. Based on this analyses, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) OF 1969 and has issued the Finding of No Significant Impact (FONSI).

  15. Environmental Assessment on the leasing of the Strategic Petroleum Reserve, St. James Terminal, St. James Parish, Louisiana

    International Nuclear Information System (INIS)

    1995-01-01

    The US Department of Energy (DOE) proposes to lease the Strategic Petroleum Reserve's (SPR) St. James Terminal to private industry. The St. James Terminal consists of six storage tanks, a pumping station, two maine docks and ancillary facilities. DOE believes that the St. James Terminal presents an opportunity to establish a government- industry arrangement that could more effectively use this asset to serve the nations's oil distribution needs, reduce the operational cost of the SPR, and provide a source of revenue for the Government. DOE solicited interest in leasing its distribution facilities in a notice published March 16, 1994. In response, industry has expressed interest in leasing the St. James Terminal, as well as several DOE pipelines, to enhance the operation of its own facilities or to avoid having to construct new ones. Under such a lease, industry use would be subordinate to DOE use in the event of a national energy emergency. This Environmental Assessment describes the proposed leasing operation, its alternatives, and potential environmental impacts. Based on this analyses, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) OF 1969 and has issued the Finding of No Significant Impact (FONSI)

  16. Insect Peptides - Perspectives in Human Diseases Treatment.

    Science.gov (United States)

    Chowanski, Szymon; Adamski, Zbigniew; Lubawy, Jan; Marciniak, Pawel; Pacholska-Bogalska, Joanna; Slocinska, Malgorzata; Spochacz, Marta; Szymczak, Monika; Urbanski, Arkadiusz; Walkowiak-Nowicka, Karolina; Rosinski, Grzegorz

    2017-01-01

    Insects are the largest and the most widely distributed group of animals in the world. Their diversity is a source of incredible variety of different mechanisms of life processes regulation. There are many agents that regulate immunology, reproduction, growth and development or metabolism. Hence, it seems that insects may be a source of numerous substances useful in human diseases treatment. Especially important in the regulation of insect physiology are peptides, like neuropeptides, peptide hormones or antimicrobial peptides. There are two main aspects where they can be helpful, 1) Peptides isolated from insects may become potential drugs in therapy of different diseases, 2) A lot of insect peptide hormones show structural or functional homology to mammalian peptide hormones and the comparative studies may give a new look on human disorders. In our review we focused on three group of insect derived peptides: 1) immune-active peptides, 2) peptide hormones and 3) peptides present in venoms. In our review we try to show the considerable potential of insect peptides in searching for new solutions for mammalian diseases treatment. We summarise the knowledge about properties of insect peptides against different virulent agents, anti-inflammatory or anti-nociceptive properties as well as compare insect and mammalian/vertebrate peptide endocrine system to indicate usefulness of knowledge about insect peptide hormones in drug design. The field of possible using of insect delivered peptide to therapy of various human diseases is still not sufficiently explored. Undoubtedly, more attention should be paid to insects due to searching new drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Human Genome Sequencing in Health and Disease

    Science.gov (United States)

    Gonzaga-Jauregui, Claudia; Lupski, James R.; Gibbs, Richard A.

    2013-01-01

    Following the “finished,” euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges. PMID:22248320

  18. James Stirling Regionalismo y modernidad

    Directory of Open Access Journals (Sweden)

    Javier de Esteban Garbayo

    2015-05-01

    Full Text Available ResumenEn los años treinta, la arquitectura moderna se había introducido en los más remotos lugares del mundo enfrentándose con la infinita idiosincrasia de lo local, y al mismo tiempo, el arquitecto, sintiendo las limitaciones de su estilo e intentando ampliar su vocabulario, se embarcó en un proceso de difusión, asimilación y personalización.La idea de una renovada época después de la posguerra británica, sería compartida por una joven generación de arquitectos con el fin de encontrar una nueva forma de modernidad.Si en sus proyectos domésticos de mediados de los cincuenta, James Stirling partió de una aproximación al regionalismo y a la 'tradición funcional' con el fin de renovar el lenguaje moderno, no abandonaría la idea 'programática' inicial de entender la arquitectura desde una consistencia formal y una lógica que combinaba 'una síntesis común del pasado reciente y una certera actitud hacia el futuro'. AbstractThirties, modern architecture had percolated into remote corners of the world, encountering the infinite idiosyncrasies of locality, and, at the same time, Architects, feelings the limitations of their style and becoming intent upon extending their vocabulary, embarked upon a process of diffusion, assimilation and personalitation.The idea of a renewed period after British postwar, was shared for a new young architects generationto find a new way of modernity.While in his mid fifties housing projects, James Stirling approached to 'regionalism' and 'the functional tradition' to renew the modern language, he wouldn't reject the programmatic idea to understand architecture from a logic and formal consistency that combine 'a common synthesis of the recent past and a certain attitude toward the future'.

  19. Finding aroma clues in the human breath to diagnose diseases

    Science.gov (United States)

    A. Dan Wilson

    2016-01-01

    History of human odor analysis in disease diagnosis The use of the sense of smell as an indicator of human disease probably originated with Hippocrates (circa 400 BC). Early medical practitioners recognized that the presence of human diseases changed the odors released from the body and breath. Physicians once relied heavily on their sense of smell to provide useful...

  20. Mitochondrial Fusion Proteins and Human Diseases

    Directory of Open Access Journals (Sweden)

    Michela Ranieri

    2013-01-01

    Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

  1. Human prion diseases in the United States.

    Directory of Open Access Journals (Sweden)

    Robert C Holman

    Full Text Available BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD, occurs worldwide. Variant CJD (vCJD, a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths. The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8% of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%; the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively. Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

  2. Nationalism in James Joyce's Ulysses

    Directory of Open Access Journals (Sweden)

    Bahee Hadaegh

    2016-03-01

    Full Text Available In the present article, the role of nationalism and postcolonialism in James Joyce's Ulysses is explored. The novel is used to reveal the political and postcolonial layers of Joyce's work and represent how colonization works through politics. This helps the readers to realize more about political Joyce and to apprehend his political views as a fresh reading of his oeuvre. The significance of this article is to depict how an author from a colonized society is influenced by the colonizing forces and cultural invasions and to scrutinize the very psychology of a colonized nation. This task is done through Attridge and Howes's methodology as the theoretical framework containing key roles in analyzing the main discussion. Through analyzing Ulysses, this article clearly shows that Joyce was a part of nationalistic movements such as the Irish Revival; however he had major conflicts with some individuals and movements that claimed to be nationalists. Therefore, Joyce is concluded to be a 'semicolonial' writer who has his own specific mode of nationalism.

  3. A chat with James Watson

    CERN Multimedia

    2011-01-01

    On 6 September, Nobel laureate James Watson paid a visit to CERN. In this interview, he shares his views with CERN's Paola Catapano.      var flash_video_player=get_video_player_path(); insert_player_for_external('Video/Public/Movies/2011/CERN-MOVIE-2011-144/CERN-MOVIE-2011-144-0753-kbps-640x360-25-fps-audio-64-kbps-44-kHz-stereo', 'mms://mediastream.cern.ch/MediaArchive/Video/Public/Movies/2011/CERN-MOVIE-2011-144/CERN-MOVIE-2011-144-0480-kbps-512x288-25-fps-audio-128-kbps-48-kHz-stereo.wmv', 'false', 480, 360, 'https://mediastream.cern.ch/MediaArchive/Video/Public/Movies/2011/CERN-MOVIE-2011-144/CERN-MOVIE-2011-144-posterframe-640x360-at-10-percent.jpg', '1384418', true, 'Video/Public/Movies/2011/CERN-MOVIE-2011-144/CERN-MOVIE-2011-144-0600-kbps-maxH-360-25-fps-audio-128-kbps-48-kHz-stereo.mp4');

  4. Obituary: James Adolph Westphal, 1930-2004

    Science.gov (United States)

    Danielson, G. Edward

    2004-12-01

    James A. Westphal died September 8, 2004. He had battled a neurological disease related to Alzheimer's for the past year. He was 74. James A. Westphal was born in Dubuque, Iowa, on June 13, 1930. He was raised in Tulsa, Oklahoma, and in Little Rock, Arkansas. Westphal earned his bachelor's degree in physics from the University of Tulsa in 1954, a year after he went to work as geophysical research group leader at Sinclair Research Lab in Tulsa. Westphal first got into the business of scientific instrumentation right after high school, when he did well-logging in Texas and Gulf Coast oil fields. In fact, his work at Sinclair Research Labs involved devising unorthodox methods for oil discovery; one of his discoveries of a new way of processing seismic data first brought him to the attention of Caltech professor Hewitt Dix, who is often considered the father of exploration geophysics. Westphal arrived at Caltech initially on a four-month leave of absence to devise a data processor for Dix, but never left. He discovered that the academic freedom individual professors enjoy was amenable to his own predilections, so he soon began branching out to other areas of scientific investigation at Caltech. Before long, he had teamed up with Bruce Murray to do thermal infrared scans of the moon in order to see if humans could even walk on the lunar surface without sinking into the dusty soil. Westphal and Murray's work showed that rocky areas could be identified with the thermal imaging, which in turn led to the inference that the Apollo astronauts could safely walk on the soil without sinking. Westphal and Murray also teamed up to do the first infrared imaging of Venus and Jupiter. Other projects at Caltech led to Westphal's being hired on permanently by Bob Sharp, who at the time was the geology division chairman. In the following years, Westphal involved himself in novel ways of studying volcanism in Hawaii and Mount St. Helens. He invented a simple and very sensitive tilt meter

  5. Role of Carbamylated Biomolecules in Human Diseases.

    Science.gov (United States)

    Badar, Asim; Arif, Zarina; Alam, Khursheed

    2018-04-01

    Carbamylation (or carbamoylation) is a non-enzymatic modification of biomolecules mediated by cyanate, a dissociation product of urea. Proteins are more sensitive to carbamylation. Two major sites of carbamylation reaction are: N α -amino moiety of a protein N-terminus and the N ɛ -amino moiety of proteins' lysine residues. In kidney diseases, urea accumulates and the burden of carbamylation increases. This may lead to alteration in the structure and function of many important proteins relevant in maintenance of homeostasis. Carbamylated proteins namely, carbamylated-haemoglobin and carbamylated-low density lipoprotein (LDL) have been implicated in hypoxia and atherosclerosis, respectively. Furthermore, carbamylation of insulin, oxytocin, and erythropoietin have caused changes in the action of these hormones vis-à-vis the metabolic pathways they control. In this short review, authors have compiled the data on role of carbamylated proteins, enzymes, hormones, LDL, and so on, in human diseases. © 2018 IUBMB Life, 70(4):267-275, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  6. St. James marine terminal facility description

    Energy Technology Data Exchange (ETDEWEB)

    1993-10-01

    The US Department of Energy (DOE) currently owns and operates a marine terminal on the west bank of the Mississippi River at St. James, Louisiana. The St. James facility was constructed by the Department to provide marine services associated with the fill and drawdown of the Strategic Petroleum Reserve (SPR) crude oil storage facilities located at Bayou Choctaw and Weeks Island, Louisiana. Although strategic to the mission of the SPR in the event of a national emergency, the St. James terminal is situated such that it has a high potential to also serve the commercial industry`s needs for crude oil terminalling and storage. The St. James terminal is located approximately 45 miles west of New Orleans and 30 miles southeast of Baton Rouge, and approximately 160 miles upstream from the mouth of the Mississippi River. Construction of the St. James terminal was initiated in 1978 and was completed in 1980. Since then, the terminal has received and transferred over 125 million barrels of crude oil to the SPR sites for storage. For crude oil distribution, the St. James terminal was connected to the neighboring LOCAP terminal by a 0.1 mile 36-inch pipeline in 1981 and to the Capline terminal by a 0.5 mile 30-inch pipeline in 1988. The terminal also has a 30-inch pipeline connection to the Koch oil terminal which was used for initial fill purposes; however, this pipeline has been disconnected and is currently inactive. A complete description of the St. James terminal facilities, operational capabilities, operational certifications, and future Government requirements are presented in Sections 2, 3, 4, and 5 respectively.

  7. Poor and Rich in James: A Relevance Theory Approach to James's Use of the Old Testament

    Science.gov (United States)

    Morales, Nelson R.

    2015-01-01

    The epistle of James was for years a forgotten book in academic circles. In recent decades, however, a renewed focus on early Judaism has generated interest in looking at James with new eyes. Poverty and wealth in the epistle continues to be a point of interest. Other topics, however, are still to be explored. One of these topics is the rhetorical…

  8. Interview with James Bradner. Interviewed by Hannah Coaker.

    Science.gov (United States)

    Bradner, James E

    2013-08-01

    James E Bradner is an Assistant Professor in Medicine at Harvard Medical School (MA, USA) as well as a Staff Physician in the Division of Hematologic Malignancies at Dana-Farber Cancer Institute (MA, USA). The present research focus of the Bradner laboratory concerns the discovery and optimization of prototype drugs targeting cancer gene regulation. The clinical objective of the Bradner group is to deliver novel therapeutics for human clinical investigation in hematologic diseases. Bradner's awards and honors include the Damon Runyon-Rachleff Innovation Award, the Smith Family Award for Excellence in Biomedical Research, the Dunkin' Donuts Rising Star Award and the HMS Distinguished Excellence in Teaching Award. He is a member of the American Society of Clinical Investigation, the American Society of Hematology, the American Chemical Society and the American Association of Cancer Research. His recent research has been published in Nature, Cell, Nature Chemical Biology and the Journal of the American Chemical Society. He has authored more than 20 US Patent applications, licensed to five pharmaceutical companies, and is a scientific founder of Acetylon Pharmaceuticals, SHAPE Pharmaceuticals, Tensha Therapeutics and Syros Pharmaceuticals. Bradner received his AB from Harvard University, his MD from the University of Chicago (IL, USA) and a MMS from Harvard Medical School. He completed his postgraduate training in Internal Medicine at Brigham & Women's Hospital (MA, USA), followed by a fellowship in Medical Oncology and Hematology at Dana-Farber Cancer Institute. Following additional post-doctoral training in Chemistry at Harvard University and the Broad Institute (MA, USA) with Professor Stuart Schreiber, Bradner joined the research faculty of Dana-Farber in 2008. Interview conducted by Hannah Coaker, Assistant Commissioning Editor.

  9. Space perception and William James's metaphysical presuppositions.

    Science.gov (United States)

    Farrell, Martin J

    2011-05-01

    William James's overtly philosophical work may be more continuous with his psychological work than is sometimes thought. His Essays in Radical Empiricism can be understood as an explicit statement of the absolute presupposition that formed the basis of Jamesian psychology: that direct experience is primary and has to be taken at face value. An examination of James's theory of space perception suggests that, even in his early work, he presupposed the primacy of direct experience, and that later changes in his account of space perception can be understood as making his view more consistent with this presupposition. In his earlier view of space perception, James argued that sensations were directly experienced as spatial, though he accepted that spatial relations between sensations may be constructed by higher order thought. In his later view, however, James argued that spatial relations were just as directly experienced as sensations. The work of T. H. Green may have prompted James to recognize the full consequence of his ideas and to realize that taking experience at face value required that spatial relations be thought of as intrinsic to experience rather than the result of intellectual construction.

  10. Beyond xeroderma pigmentosum: DNA damage and repair in an ecological context. A tribute to James E. Cleaver.

    Science.gov (United States)

    Karentz, Deneb

    2015-01-01

    The ability to repair DNA is a ubiquitous characteristic of life on Earth and all organisms possess similar mechanisms for dealing with DNA damage, an indication of a very early evolutionary origin for repair processes. James E. Cleaver's career (initiated in the early 1960s) has been devoted to the study of mammalian ultraviolet radiation (UVR) photobiology, specifically the molecular genetics of xeroderma pigmentosum and other human diseases caused by defects in DNA damage recognition and repair. This work by Jim and others has influenced the study of DNA damage and repair in a variety of taxa. Today, the field of DNA repair is enhancing our understanding of not only how to treat and prevent human disease, but is providing insights on the evolutionary history of life on Earth and how natural populations are coping with UVR-induced DNA damage from anthropogenic changes in the environment such as ozone depletion. © 2014 The American Society of Photobiology.

  11. Analogs of human genetic skin disease in domesticated animals

    Directory of Open Access Journals (Sweden)

    Justin Finch, MD

    2017-09-01

    The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.

  12. William James, Gustav Fechner, and Early Psychophysics

    Directory of Open Access Journals (Sweden)

    Stephanie L. Hawkins

    2011-10-01

    Full Text Available American psychologist and philosopher William James devoted the entirety of his career to exploring the nature of volition, as expressed by such phenomena as will, attention, and belief. As part of that endeavor, James's unorthodox scientific pursuits, from his experiments with nitrous oxide and hallucinogenic drugs to his investigation of spiritualist mediums, represent his attempt to address the "hard problems" of consciousness for which his training in brain physiology and experimental psychology could not entirely account. As a student, James's reading in chemistry and physics had sparked his interest in the concepts of energy and force, terms that he later deployed in his writing about consciousness and in his arguments against philosophical monism and scientific materialism, as he developed his radically empiricist ideas privileging discontinuity and plurality. Despite James's long campaign against scientific materialism, he was, however, convinced of the existence of a naturalistic explanation for the more "wayward and fitful" aspects of mind, including transcendent experiences associated with hysteria, genius, and religious ecstasy. In this paper, I examine aspects of James's thought that are still important for contemporary debates in psychology and neuroscience: his "transmission theory" of consciousness, his ideas on the "knowing of things together," and, finally, the related concept of "the compounding of consciousness," which postulates the theoretical possibility for individual entities within a conscious system of thought to "know" the thoughts of others within the system. Taken together, these ideas suggest that James, in spite of, or perhaps because of, his forays into metaphysics, was working toward a naturalistic understanding of consciousness, what I will term a "distributive model," based on his understanding of consciousness as an "awareness" that interacts dynamically within, and in relation to, its environment.

  13. In conversation with: Professor Richard James

    Directory of Open Access Journals (Sweden)

    John Clarke

    2014-03-01

    Full Text Available In 2011, Richard James wrote in the Foreword to Nelson, Clarke, Kift, and Creagh’s (2012 monograph on Australasian literature on the First Year Experience that:The trend towards universal participation will usher in dramatic changes in the character of the first year in higher education. … (p. iiiIn an interview at the University of Melbourne, Australia in July 2013 between Richard James and John Clarke, Co-editor of the International Journal of the First Year in Higher Education, these and related issues were explored.  The interview picks up where the Foreword left off:  focussing on universal participation.

  14. James Madison University Survey of Faculty Activities.

    Science.gov (United States)

    James Madison Univ., Harrisonburg, VA.

    The activities of the faculty at James Madison University during the fall term of the academic year 1978-79 are described. Full-time instructional faculty, part-time faculty involved in resident instruction, administrators and classified employees who taught at least one course, and graduate teaching assistants were surveyed. Information was…

  15. "Restructuring" Stirs Outcry at James Madison.

    Science.gov (United States)

    Magner, Denise K.

    1995-01-01

    An administration plan to discontinue the physics major at James Madison University (Virginia) has raised concerns about the president's leadership and management style, and the role of faculty in institutional decision making. Faculty were notified of the plan only after student leaders were told. (MSE)

  16. James Madison and "The Federalist Papers."

    Science.gov (United States)

    Patrick, John J.; And Others

    A collection of resources for high school history and government teachers and their students, this volume treats core ideas on constitutional government in the United States. James Madison's ideas as found in "The Federalist Papers" are examined in conjunction with their counterpoints in essays of the Anti-Federalists. This volume…

  17. James Madison and the Constitutional Convention.

    Science.gov (United States)

    Scanlon, Thomas M.

    1987-01-01

    Part 1 of this three-part article traces James Madison's life and focuses primarily on those events that prepared him for leadership in the U.S. Constitutional Convention of 1787. It describes his early love of learning, education, and public service efforts. Part 2 chronicles Madison's devotion to study and preparation prior to the Constitutional…

  18. James Bernard Russell: Scholar, collaborator, mentor

    Science.gov (United States)

    At the time of his untimely death in 2009, ARS scientist Dr. James B. Russell had established himself as the premier rumen microbiologist of his generation. Dr. Russell’s many contributions to the field, including much of the early work on the Cornell Net Carbohydrate System model, were the product ...

  19. Entomologic index for human risk of Lyme disease.

    Science.gov (United States)

    Mather, T N; Nicholson, M C; Donnelly, E F; Matyas, B T

    1996-12-01

    An entomologic index based on density estimates of Lyme disease spirochete-infected nymphal deer ticks (lxodes scapularis) was developed to assess human risk of Lyme disease. The authors used a standardized protocol to determine tick density and infection in numerous forested sites in six Rhode Island towns. An entomologic risk index calculated for each town was compared with the number of human Lyme disease cases reported to the Rhode Island State Health Department for the same year. A strong positive relation between entomologic risk index and the Lyme disease case rate for each town suggested that the entomologic index was predictive of Lyme disease risk.

  20. Nutrition, epigenetic mechanisms, and human disease

    National Research Council Canada - National Science Library

    Maulik, Nilanjana; Maulik, Gautam

    2011-01-01

    .... The text discusses the basics of nutrigenomics and epigenetic regulation, types of nutrition influencing genetic imprinting, and the role of nutrition in modulating an individual's predisposition to disease...

  1. Tribute to the legend Mr. Veterinary Public Health, Professor James ...

    African Journals Online (AJOL)

    The author was also destined during his Sabbatical Leave to have an interactive interview session with Prof James Steele after attending the 20th Annual James Steele lecture/ 99th birthday Dinner of Professor James Steele 4th and 6th April 2012 at the Texas School of Public Health, Houston, Texas, USA. The interview ...

  2. Multinational corporations and infectious disease: Embracing human rights management techniques.

    Science.gov (United States)

    Salcito, Kendyl; Singer, Burton H; Weiss, Mitchell G; Winkler, Mirko S; Krieger, Gary R; Wielga, Mark; Utzinger, Jürg

    2014-01-01

    Global health institutions have called for governments, international organisations and health practitioners to employ a human rights-based approach to infectious diseases. The motivation for a human rights approach is clear: poverty and inequality create conditions for infectious diseases to thrive, and the diseases, in turn, interact with social-ecological systems to promulgate poverty, inequity and indignity. Governments and intergovernmental organisations should be concerned with the control and elimination of these diseases, as widespread infections delay economic growth and contribute to higher healthcare costs and slower processes for realising universal human rights. These social determinants and economic outcomes associated with infectious diseases should interest multinational companies, partly because they have bearing on corporate productivity and, increasingly, because new global norms impose on companies a responsibility to respect human rights, including the right to health. We reviewed historical and recent developments at the interface of infectious diseases, human rights and multinational corporations. Our investigation was supplemented with field-level insights at corporate capital projects that were developed in areas of high endemicity of infectious diseases, which embraced rights-based disease control strategies. Experience and literature provide a longstanding business case and an emerging social responsibility case for corporations to apply a human rights approach to health programmes at global operations. Indeed, in an increasingly globalised and interconnected world, multinational corporations have an interest, and an important role to play, in advancing rights-based control strategies for infectious diseases. There are new opportunities for governments and international health agencies to enlist corporate business actors in disease control and elimination strategies. Guidance offered by the United Nations in 2011 that is widely embraced

  3. The genus Malassezia and human disease

    Directory of Open Access Journals (Sweden)

    Inamadar A

    2003-07-01

    Full Text Available Sabouraud's Pityrosporum is now recognized as Malassezia. With taxonomic revision of the genus, newer species have been included. The role of this member of the normal human skin flora in different cutaneous and systemic disorders is becoming clearer. The immunological responses it induces in the human body are conflicting and their relevance to clinical features is yet to be explored.

  4. Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

    Science.gov (United States)

    Barruet, Emilie; Hsiao, Edward C

    2016-01-01

    Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

  5. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    Science.gov (United States)

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

  6. Chronic Inflammatory Periodontal Disease in Patients with Human Immunodeficiency Virus.

    OpenAIRE

    Vania López Rodríguez; Emilio Carpio Muñoz; Vicente Fardales Macías; Iralys Benítez Guzmán

    2009-01-01

    Background: The Chronic Inflammatory Periodontal Disease is related with multiple risk factors. Those patients with human immunodeficiency virus have higher risk of presenting this disease and it is usually more serious in these cases. Objective: To describe the prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV. Methods: Descriptive, observational, cross-sectional study including patients with HIV in Sancti Spiritus province. The occurrence of the disease was determi...

  7. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2015-08-01

    Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

  8. Disease emergence and resurgence—the wildlife-human connection

    Science.gov (United States)

    Friend, Milton; Hurley, James W.; Nol, Pauline; Wesenberg, Katherine

    2006-01-01

    In 2000, the Global Outbreak Alert and Response Network (GOARN) was organized as a global disease watchdog group to coordinate disease outbreak information and health crisis response. The World Health Organization (WHO) is the headquarters for this network. Understandably, the primary focus for WHO is human health. However, diseases such as the H5N1 avian influenza epizootic in Asian bird populations demonstrate the need for integrating knowledge about disease emergence in animals and in humans.Aside from human disease concerns, H5N1 avian influenza has major economic consequences for the poultry industry worldwide. Many other emerging diseases, such as severe acute respiratory syndrome (SARS), monkeypox, Ebola fever, and West Nile fever, also have an important wildlife component. Despite these wildlife associations, the true integration of the wildlife component in approaches towards disease emergence remains elusive. This separation between wildlife and other species’ interests is counterproductive because the emergence of zoonotic viruses and other pathogens maintained by wildlife reservoir hosts is poorly understood.This book is about the wildlife component of emerging diseases. It is intended to enhance the reader’s awareness of the role of wildlife in disease emergence. By doing so, perhaps a more holistic approach to disease prevention and control will emerge for the benefit of human, domestic animal, and free-ranging wildlife populations alike. The perspectives offered are influenced by more than four decades of my experiences as a wildlife disease practitioner. Although wildlife are victims to many of the same disease agents affecting humans and domestic animals, many aspects of disease in free-ranging wildlife require different approaches than those commonly applied to address disease in humans or domestic animals. Nevertheless, the broader community of disease investigators and health care professionals has largely pursued a separatist approach for

  9. Disease Human - MDC_CardiovascularMortality2006

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Polygon feature class based on Zip Code boundaries showing the rate of deaths due to major cardiovascular diseases per 1000 residents of Miami-Dade County in 2006.

  10. Disease Human - MDC_CLRDMortality2006

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Polygon feature class based on Zip Code boundaries showing the rate of deaths per 100,000 residents due to Chronic Lower Respiratory Disease (CLRD) in Miami-Dade...

  11. In Memoriam: James Harlan Steele (1913—2013)

    Centers for Disease Control (CDC) Podcasts

    2014-05-19

    Drs. Jennifer McQuiston and Casey Barton Behravesh talk with Dr. Myron Schultz about the legendary Dr. James Harlan Steele.  Created: 5/19/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 5/20/2014.

  12. 76 FR 54382 - Safety Zone; Labor Day Fireworks, Ancarrows Landing Park, James River, Richmond, VA

    Science.gov (United States)

    2011-09-01

    ... the shoreline of the navigable waters of the James River centered on position 37[deg]31'13.1'' N..., performance, design, or operation; test methods; sampling procedures; and related management systems practices... which do not individually or cumulatively have a significant effect on the human environment. This rule...

  13. 77 FR 27118 - Safety Zone; Rocketts Red Glare Fireworks, Ancarrows Landing Park, James River, Richmond, VA

    Science.gov (United States)

    2012-05-09

    ... waters of the James River centered on position 37[deg]31'13.1'' N/077[deg]25'07.84'' W (NAD 1983). Due to... are technical standards (e.g., specifications of materials, performance, design, or operation; test... cumulatively have a significant effect on the human environment. This rule is categorically excluded, under...

  14. [Delocalizing the mind. Peirce, James, Wittgenstein, Descombes].

    Science.gov (United States)

    Chauviré, Christiane

    2010-01-01

    The cognitive sciences have breathed fresh air into the old problem of localizing mental functions, which was often laughed off. Regarding the most philosophical form of the question on the localization of the mind, authors such as Peirce, James, Wittgenstein, and most recently Descombes have imagined delocalizing the mind in order to spread the conviction that the idea itself of a location of the mental is meaningless and to criticize the localisationism of today's cognitive scientists.

  15. William James and the Heidelberg fiasco.

    Science.gov (United States)

    Gundlach, Horst

    2018-02-01

    Urged on by his father to become a physician instead of a painter, William James pursued 3 evasion stratagems. First, to avoid becoming a practitioner, he declared that he wanted to specialize in physiology. Based upon this premise, he left for Germany in the spring of 1867. The second step was giving up general physiology and announcing that he would specialize in the nervous system and psychology. Based upon this premise, he declared that he would go to Heidelberg and study with Helmholtz and Wundt. However, he then deferred going there. When, at last, he was urged by an influential friend of his father's to accompany him to Heidelberg, he employed his default stratagem: He simply fled. He returned home after 3 terms in Europe without enrolling at a single university. There is no evidence that he had learned anything there about psychology or experimental psychology, except, possibly, by reading books. James's "Heidelberg fiasco" was the apogee of his evasion of his father's directive. A dense fog of misinformation surrounds his stay in Heidelberg to this day. By analyzing circumstances and context, this article examines the fiasco and places it in the pattern of his behavior during his stay in Europe. Nevertheless, experiencing this fiasco potentially shaped James's ambivalent attitude toward experimental psychology on a long-term basis. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  16. Emerging role of mitophagy in human diseases and physiology.

    Science.gov (United States)

    Um, Jee-Hyun; Yun, Jeanho

    2017-06-01

    Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machinery. Mitophagy plays an essential role in maintaining mitochondrial quality control and homeostasis. Mitochondrial dysfunctions and defective mitophagy in neurodegenerative diseases, cancer, and metabolic diseases indicate a close link between human disease and mitophagy. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment. This review mainly focuses on the recent implications for mitophagy in human diseases and normal physiology. [BMB Reports 2017; 50(6): 299-307].

  17. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

    DEFF Research Database (Denmark)

    Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie

    2016-01-01

    The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells...... chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends...

  18. Vitamins in the prevention of human diseases

    National Research Council Canada - National Science Library

    Herrmann, Wolfgang, Prof; Obeid, Rima

    2011-01-01

    ... in ancient Egypt. One-sided nutrition, smoking, alcohol, genetic factors, and even geographical origin interfere with our dietary intake of the vitamins. Insufficient vitamin intake can impact our health and contribute significantly to the development of diseases. This book offers expert reviews and judgements on the role of vitamins in health and ...

  19. Exposure to Human Immunodeficiency Disease. What Precautions ...

    African Journals Online (AJOL)

    Background: The Human Immunodeficiency Virus (HIV) epidemic is more pronounced in sub-Saharan Africa. The ever-increasing prevalence of HIV infection and the continued improvement in clinical management has increased the likelihood of these patients being managed by healthcare workers. The aim of the review ...

  20. Skin Diseases: Cross-section of human skin

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Cross-section of human skin Past Issues / Fall 2008 Table of Contents For ... Logical Images, Inc. I n the areas of skin health and skin diseases, the NIH's National Institute ...

  1. Glutathione dysregulation and the etiology and progression of human diseases.

    NARCIS (Netherlands)

    Ballatori, N.; Krance, S.M.; Notenboom, S.; Shi, S.; Tieu, K.; Hammond, C.L.

    2009-01-01

    Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases

  2. Mosquitoes as vectors of human disease in South Africa | Jupp ...

    African Journals Online (AJOL)

    While malaria is the most important mosquito-borne disease in South Africa, there are also several mosquito-borne viruses that also cause human disease. The most significant are chikungunya, West Nile, Sindbis and Rift Valley fever viruses. In this review these are compared with malaria, mainly in regard to their ecology ...

  3. A murine model of human myeloma bone disease

    NARCIS (Netherlands)

    Garrett, I.R.; Dallas, S.; Radl, J.; Mundy, G.R.

    1997-01-01

    Myeloma causes a devastating and unique form of osteolytic bone disease. Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast activity have not been defined. An animal model of human myeloma bone disease mould help in

  4. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  5. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  6. Positions of human dwellings affect few tropical diseases near ...

    African Journals Online (AJOL)

    user

    Some factors that possibly affect tropical disease distribution was investigated in about 500 randomize human dwellings. The studied factors include wild animals, domestic animals, wild plants, cultivated plants, nature of soil, nature of water, positions of human dwellings, nature of building material and position of animal ...

  7. Animal models for human genetic diseases | Sharif | African Journal ...

    African Journals Online (AJOL)

    The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...

  8. Multifractal Detrended Fluctuation Analysis of Human gait Diseases

    Directory of Open Access Journals (Sweden)

    Srimonti eDutta

    2013-10-01

    Full Text Available IIn this paper multifractal detrended fluctuation analysis is used to study the human gait time series for normal and diseased sets. It is observed that long range correlation is primarily responsible for the origin of multifractality. The study reveals that the degree of multifractality is more for normal set compared to diseased set. However the method fails to distinguish between the two diseased sets.

  9. DEGAS: de novo discovery of dysregulated pathways in human diseases.

    Directory of Open Access Journals (Sweden)

    Igor Ulitsky

    Full Text Available BACKGROUND: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression is significantly dysregulated in sick individuals compared to healthy controls. Recent studies have found that only a small number of the genes in human disease-related pathways show consistent dysregulation in sick individuals. However, those studies found that some pathway genes are affected in most sick individuals, but genes can differ among individuals. While a pathway is usually defined as a set of genes known to share a specific function, pathway boundaries are frequently difficult to assign, and methods that rely on such definition cannot discover novel pathways. Protein interaction networks can potentially be used to overcome these problems. METHODOLOGY/PRINCIPAL FINDINGS: We present DEGAS (DysrEgulated Gene set Analysis via Subnetworks, a method for identifying connected gene subnetworks significantly enriched for genes that are dysregulated in specimens of a disease. We applied DEGAS to seven human diseases and obtained statistically significant results that appear to home in on compact pathways enriched with hallmarks of the diseases. In Parkinson's disease, we provide novel evidence for involvement of mRNA splicing, cell proliferation, and the 14-3-3 complex in the disease progression. DEGAS is available as part of the MATISSE software package (http://acgt.cs.tau.ac.il/matisse. CONCLUSIONS/SIGNIFICANCE: The subnetworks identified by DEGAS can provide a signature of the disease potentially useful for diagnosis, pinpoint possible pathways affected by the disease, and suggest targets for drug intervention.

  10. [Bartonellosis. II. Other Bartonella responsible for human diseases].

    Science.gov (United States)

    Piémont, Y; Heller, R

    1999-01-01

    In addition to Bartonella henselae, five other Bartonella species were involved in human pathology. As for B. henselae, ectoparasites seem to be responsible for the transmission of most or all these bacterial species. B. bacilliformis is responsible for Carrion's disease that occurs in some valleys of Colombia, Ecuador and Peru. This disease is transmitted by biting of infected sandflies. The bacterial reservoir is constituted by humans only. That disease occurs either as an acute form with severe infectious hemolytic anemia (or Oroya fever), or as benign cutaneous tumors, also called verruga peruana. Healthy blood carriers of the bacterium exist. Trench fever was described during the First World War. This non-lethal disease is constituted of recurrent febrile attacks associated particularly with osseous pains. The causative agent of the disease is B. quintana, transmitted by the body louse. Humans seem to be the reservoir of that bacterium. In some patients, B. quintana can be responsible for endocarditis, bacillary angiomatosis and chronic or recurrent bacteremia. Other human infections due to Bartonella sp. have been described: B. vinsonii, isolated from blood of small rodents, and B. elizabethae, the reservoir of which is currently unknown, can be responsible for endocardites. B. clarridgeiae (isolated from blood of 5% of pet cats and 17% of stray cats) may be responsible for human cat scratch disease. All these bartonelloses are diagnosed by non-standard blood culture or by in vitro DNA amplification or by serological testing. Their treatment requires tetracyclines or chloramphenicol or macrolides.

  11. James Bernoulli与《推测术》%James Bernoulli and Stochastics

    Institute of Scientific and Technical Information of China (English)

    于忠义

    2003-01-01

    Two hundred and eighty-nine years ago, "Arts of conjecturing", the posthumous work of the great mathematician James Bernoulli, was finally produced in the eager wait of mathematicians, Ian Hacking, a famous historian of statistics, commented that the publication of the book signaled the beginning of the mathematical theory of probability and terminated man's long process in the forming of the probability concept By introducing James Bernoulli and his "Arts of conjecturing", this paper aims at providing the reader with the 18th century story of Bemoulli's work, and at making the reader know that even today Bemoulli's idea is very helpful and instructive in the research of modern statistics.

  12. Impacts of Gut Bacteria on Human Health and Diseases

    Science.gov (United States)

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  13. Wildlife disease prevalence in human-modified landscapes.

    Science.gov (United States)

    Brearley, Grant; Rhodes, Jonathan; Bradley, Adrian; Baxter, Greg; Seabrook, Leonie; Lunney, Daniel; Liu, Yan; McAlpine, Clive

    2013-05-01

    Human-induced landscape change associated with habitat loss and fragmentation places wildlife populations at risk. One issue in these landscapes is a change in the prevalence of disease which may result in increased mortality and reduced fecundity. Our understanding of the influence of habitat loss and fragmentation on the prevalence of wildlife diseases is still in its infancy. What is evident is that changes in disease prevalence as a result of human-induced landscape modification are highly variable. The importance of infectious diseases for the conservation of wildlife will increase as the amount and quality of suitable habitat decreases due to human land-use pressures. We review the experimental and observational literature of the influence of human-induced landscape change on wildlife disease prevalence, and discuss disease transmission types and host responses as mechanisms that are likely to determine the extent of change in disease prevalence. It is likely that transmission dynamics will be the key process in determining a pathogen's impact on a host population, while the host response may ultimately determine the extent of disease prevalence. Finally, we conceptualize mechanisms and identify future research directions to increase our understanding of the relationship between human-modified landscapes and wildlife disease prevalence. This review highlights that there are rarely consistent relationships between wildlife diseases and human-modified landscapes. In addition, variation is evident between transmission types and landscape types, with the greatest positive influence on disease prevalence being in urban landscapes and directly transmitted disease systems. While we have a limited understanding of the potential influence of habitat loss and fragmentation on wildlife disease, there are a number of important areas to address in future research, particularly to account for the variability in increased and decreased disease prevalence. Previous studies

  14. Obituary: James Gilbert Baker, 1914-2005

    Science.gov (United States)

    Baker, Neal Kenton

    2005-12-01

    (1970), the American Academy of Arts and Sciences (1946), and the National Academy of Engineering (1979). He was a member of the American Astronomical Society, the International Astronomical Union, and the Astronomical Society of the Pacific. He authored numerous professional papers and has over fifty US patents. He maintained his affiliation with the Harvard College Observatory and the Smithsonian Astrophysical Observatory until he retired in 2003. Even after his retirement in 2003, he continued work at his home on a new telescope design that he told his family he should have discovered in 1940. Light was always his tool to the understanding of the Universe. An entry from his personal observation log, 7 January 1933, made after an evening of star gazing reveals the pure inspiration of his efforts: "After all, it is the satisfaction obtained which benefits humanity, more than any other thing. It is in the satisfaction of greater human knowledge about the cosmos that the scientist is spurred on to greater efforts." James Baker fulfilled the destiny he had foreseen in 1933, living to see professional and amateur astronomers use his instruments and designs to further the understanding of the cosmos. Whereas, he had not predicted that his cameras would protect this nation for over many years. He is survived by his wife, his four children and five grandchildren. 1Oscar Bryant, "Astronomical Designs," in "Accent", the University of Louisville College of Arts and Sciences Alumni Newsletter, Spring 1994. 2George W. Goddard,Brigadier General, "Overview", 273.

  15. FISH CONSUMPTION, METHYLMERCURY, AND HUMAN HEART DISEASE.

    Energy Technology Data Exchange (ETDEWEB)

    LIPFERT, F.W.; SULLIVAN, T.M.

    2005-09-21

    Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased mortality risks

  16. A case of Swyer-James syndrome

    International Nuclear Information System (INIS)

    Suzuki, Toshimitsu; Ohtani, Naoshi; Kimura, Sohichi; Izuchi, Rokuro; Iio, Masaaki; Fujinami, Kenji.

    1982-01-01

    Infantile infections are thought to constitute one of the main bases of the etiology of Swyer-James syndrome. This case seems to support the above theory allowing for the anamnesis of the pleuritis at 2 years of age, bronchographical findings - bilateral but markedly left-sided bud-like bronchiectatic changes - and left pulmonary angiographical findings - simultaneous appearance of pulmonary arteries and veins with scarce capillary image. Concerning the ventilation of this syndrome, 133 Xe inhalation test showed a ''Pendelluft'' phenomenon, shift of 133 Xe from the healthy to the affected lung on forced expiration. (author)

  17. Human genomic disease variants: a neutral evolutionary explanation.

    Science.gov (United States)

    Dudley, Joel T; Kim, Yuseob; Liu, Li; Markov, Glenn J; Gerold, Kristyn; Chen, Rong; Butte, Atul J; Kumar, Sudhir

    2012-08-01

    Many perspectives on the role of evolution in human health include nonempirical assumptions concerning the adaptive evolutionary origins of human diseases. Evolutionary analyses of the increasing wealth of clinical and population genomic data have begun to challenge these presumptions. In order to systematically evaluate such claims, the time has come to build a common framework for an empirical and intellectual unification of evolution and modern medicine. We review the emerging evidence and provide a supporting conceptual framework that establishes the classical neutral theory of molecular evolution (NTME) as the basis for evaluating disease- associated genomic variations in health and medicine. For over a decade, the NTME has already explained the origins and distribution of variants implicated in diseases and has illuminated the power of evolutionary thinking in genomic medicine. We suggest that a majority of disease variants in modern populations will have neutral evolutionary origins (previously neutral), with a relatively smaller fraction exhibiting adaptive evolutionary origins (previously adaptive). This pattern is expected to hold true for common as well as rare disease variants. Ultimately, a neutral evolutionary perspective will provide medicine with an informative and actionable framework that enables objective clinical assessment beyond convenient tendencies to invoke past adaptive events in human history as a root cause of human disease.

  18. Drosophila tools and assays for the study of human diseases

    Directory of Open Access Journals (Sweden)

    Berrak Ugur

    2016-03-01

    Full Text Available Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes.

  19. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis.

    Science.gov (United States)

    2012-01-01

    This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html.

  20. Polycystins, calcium signaling, and human diseases

    International Nuclear Information System (INIS)

    Delmas, Patrick; Padilla, Francoise; Osorio, Nancy; Coste, Bertrand; Raoux, Matthieu; Crest, Marcel

    2004-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a major, inherited nephropathy affecting over 1:1000 of the worldwide population. It is a systemic condition with frequent hepatic and cardiovascular manifestations in addition to the progressive development of fluid-filled cysts from the tubules and collecting ducts of affected kidneys. The pathogenesis of cyst formation is currently thought to involve increased proliferation of epithelial cells, mild dedifferentiation, and fluid accumulation. In the past decade, study of ADPKD led to the discovery of a unique family of highly complex proteins, the polycystins. Loss-of-function mutations in either of two polycystin proteins, polycystin-1 or polycystin-2, give rise to ADPKD. These proteins are thought to function together as part of a multiprotein complex that may initiate Ca 2+ signals, directing attention to the regulation of intracellular Ca 2+ as a possible misstep that participates in cyst formation. Here we review what is known about the Ca 2+ signaling functions of polycystin proteins and focus on findings that have significantly advanced our physiological insight. Special attention is paid to the recently discovered role of these proteins in the mechanotransduction of the renal primary cilium and the model it suggests

  1. Rare human diseases: 9p deletion syndrome

    Directory of Open Access Journals (Sweden)

    Galagan V.O.

    2014-09-01

    Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.

  2. THE QUEST FOR KNOWLEDGE IN "THE KING JAMES BIBLE"

    Directory of Open Access Journals (Sweden)

    Ewa Piotrowska-Oberda

    2014-10-01

    Full Text Available The aim of this article is the quest for knowledge in "The King James Bible" (1611 in terms of quantitative and qualitative research methodology with the application of the statistical analysis tool Antconc. The quest for knowledge with the use of corpus research aims at discussing the Biblical concept of knowledge through the origin, the object of knowledge, its implications and its constant development. Knowledge is often seen as of divine nature, reflected in the soul of man. It is based not only on logical, but also on the spiritual and ethical reasoning. The object of knowledge is light, reflecting the divine nature of knowledge which exceeds the intellect to reach a deeper spiritual human reasoning. In "The King James Bible" (1611 the authors of New Testament consider human knowledge to be imperfect and partial. They emphasize the need for a spiritual man aiming at reaching a complete knowledge. This spiritual development is based on the relationship between knowledge and faith, as well as knowledge and love. For the authors of the books of the New Testament there is no dichotomy between both knowledge and faith and knowledge and love, because faith and love depend on knowledge that originates in the word of God and leads to spiritual development. From this perspective, religious knowledge, love and mercy as well as faith developed through the knowledge of the biblical text leads to the knowledge of God, the enlightening source of ultimate knowledge. Thus, in the spiritual development of man not only the knowledge and faith but also emotional intelligence, which expresses itself through love and charity as the safer guide in all controversial issues, are important.

  3. Infectious prion diseases in humans: cannibalism, iatrogenicity and zoonoses.

    Science.gov (United States)

    Haïk, Stéphane; Brandel, Jean-Philippe

    2014-08-01

    In contrast with other neurodegenerative disorders associated to protein misfolding, human prion diseases include infectious forms (also called transmitted forms) such as kuru, iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal isoform (PrP(Sc)) of the host-encoded prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the biological properties of the various prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human prion diseases played a pivotal role in the emergence of the prion concept and in the characterization of the very unconventional properties of prions. They provide a unique model to understand how prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence disease susceptibility, incubation period and phenotypic expression in the light of the kuru epidemics due to ritual endocannibalism, the various series iatrogenic diseases secondary to extractive growth hormone treatment or dura mater graft and the epidemics of variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of bovine spongiform encephalopathy. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  5. Kuula. Kellele ei meeldiks James Blunt? / Mart Juur

    Index Scriptorium Estoniae

    Juur, Mart, 1964-

    2007-01-01

    Heliplaatidest: James Blunt "Back To Bedlam", Enrique Iglesias "Insomniac", Prince "Planet Earth", Garbage "Absolut Garbage", Justice "Cross", Interpol "Our Love To Admire", Rufus Wainwright "Release The Stars"

  6. Henry James – Modern Theoretician of Narration

    Directory of Open Access Journals (Sweden)

    Alexandra - Denisa IGNA

    2013-01-01

    Full Text Available Henry James, properly named world writer, was one of the first modern novelists, with an exigent writing conscience. The American writer subverted the prejudgement of the omniscient author in favour of the narration which is centred on the characters’ point of view, thus modernising the novel before V. Woolf, Huxley, Thomas Mann, or in our case Camil Petrescu and G. Călinescu. Some bio-bibliographical information familiarises the reader with the life and work of this writer. The larger part of the article is dedicated to a case study of the novel with the metaphorical title: The Figure in the Carpet, where Henry James tries to illustrate in an artistic manner his conception regarding the profundity and ineffability of the literary creation. The conclusion which the author reaches, alternating the familiar plan of the relationship between a married couple with the esthetical plan, is that the relationship between writer and his work represents an act of fully intimacy, just like a ceremony that takes place in the wedding night

  7. Genetic engineering in nonhuman primates for human disease modeling.

    Science.gov (United States)

    Sato, Kenya; Sasaki, Erika

    2018-02-01

    Nonhuman primate (NHP) experimental models have contributed greatly to human health research by assessing the safety and efficacy of newly developed drugs, due to their physiological and anatomical similarities to humans. To generate NHP disease models, drug-inducible methods, and surgical treatment methods have been employed. Recent developments in genetic and developmental engineering in NHPs offer new options for producing genetically modified disease models. Moreover, in recent years, genome-editing technology has emerged to further promote this trend and the generation of disease model NHPs has entered a new era. In this review, we summarize the generation of conventional disease model NHPs and discuss new solutions to the problem of mosaicism in genome-editing technology.

  8. Natural selection and infectious disease in human populations

    Science.gov (United States)

    Karlsson, Elinor K.; Kwiatkowski, Dominic P.; Sabeti, Pardis C.

    2015-01-01

    The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. PMID:24776769

  9. Human genetics of infectious diseases: a unified theory

    OpenAIRE

    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

    Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predispos...

  10. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  11. Linking adult hippocampal neurogenesis with human physiology and disease.

    Science.gov (United States)

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Interconnectivity of human cellular metabolism and disease prevalence

    Science.gov (United States)

    Lee, Deok-Sun

    2010-12-01

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease-gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery.

  13. Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

    Science.gov (United States)

    Bonda, David J; Manjila, Sunil; Mehndiratta, Prachi; Khan, Fahd; Miller, Benjamin R; Onwuzulike, Kaine; Puoti, Gianfranco; Cohen, Mark L; Schonberger, Lawrence B; Cali, Ignazio

    2016-07-01

    The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission

  14. Bowen's Disease Associated With Two Human Papilloma Virus Types.

    Science.gov (United States)

    Eftekhari, Hojat; Gharaei Nejad, Kaveh; Azimi, Seyyede Zeinab; Rafiei, Rana; Mesbah, Alireza

    2017-09-01

    Bowen's disease (BD) is an epidermal in-situ squamous cell carcinoma (SCC). Most Human Papilloma Viruses (HPV)-positive lesions in Bowen's disease are localized to the genital region or distal extremities (periungual sites) in which HPV type-16 is frequently detected. Patient was a 64-year-old construction worker for whom we detected 2 erythematous psoriasiform reticular scaly plaques on peri-umbilical and medial knee. Biopsy established the diagnosis of Bowen's disease and polymerase chain reaction assay showed HPV-6, -18 co-infection. Patient was referred for surgical excision.

  15. Human gene therapy and imaging in neurological diseases

    International Nuclear Information System (INIS)

    Jacobs, Andreas H.; Winkler, Alexandra; Castro, Maria G.; Lowenstein, Pedro

    2005-01-01

    Molecular imaging aims to assess non-invasively disease-specific biological and molecular processes in animal models and humans in vivo. Apart from precise anatomical localisation and quantification, the most intriguing advantage of such imaging is the opportunity it provides to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Further, molecular imaging can be used to address basic scientific questions, e.g. transcriptional regulation, signal transduction or protein/protein interaction, and will be essential in developing treatment strategies based on gene therapy. Most importantly, molecular imaging is a key technology in translational research, helping to develop experimental protocols which may later be applied to human patients. Over the past 20 years, imaging based on positron emission tomography (PET) and magnetic resonance imaging (MRI) has been employed for the assessment and ''phenotyping'' of various neurological diseases, including cerebral ischaemia, neurodegeneration and brain gliomas. While in the past neuro-anatomical studies had to be performed post mortem, molecular imaging has ushered in the era of in vivo functional neuro-anatomy by allowing neuroscience to image structure, function, metabolism and molecular processes of the central nervous system in vivo in both health and disease. Recently, PET and MRI have been successfully utilised together in the non-invasive assessment of gene transfer and gene therapy in humans. To assess the efficiency of gene transfer, the same markers are being used in animals and humans, and have been applied for phenotyping human disease. Here, we review the imaging hallmarks of focal and disseminated neurological diseases, such as cerebral ischaemia, neurodegeneration and glioblastoma multiforme, as well as the attempts to translate gene therapy's experimental knowledge into clinical applications and the way in which this process is being promoted through the use of

  16. The delusion of the Master: the last days of Henry James.

    Science.gov (United States)

    Bartolomeo, Paolo

    2013-11-01

    The novelist Henry James shared with his brother William, the author of the Principles of Psychology, a deep interest in the ways in which personal identity is built through one's history and experiences. At the end of his life, Henry James suffered a vascular stroke in the right hemisphere and developed a striking identity delusion. He dictated in a perfectly clear and coherent manner two letters as if they were written by Napoleon Bonaparte. He also showed signs of reduplicative paramnesia. Negative symptoms resulting from right hemisphere damage may disrupt the feelings of "warmth and intimacy and immediacy" and the "resemblance among the parts of a continuum of feelings (especially bodily feelings)", which are the foundation of personal identity according to William James. On the other hand, a left hemisphere receiving inadequate input from the damaged right hemisphere may produce positive symptoms such as delusional, confabulatory narratives. Other fragments dictated during Henry James's final disease reveal some form of insight, if partial and disintegrated, into his condition. Thus, even when consciousness is impaired by brain damage, something of its deep nature may persist, as attested by the literary characteristics of the last fragments of the Master.

  17. Effects of antibiotics on human microbiota and subsequent disease.

    Science.gov (United States)

    Keeney, Kristie M; Yurist-Doutsch, Sophie; Arrieta, Marie-Claire; Finlay, B Brett

    2014-01-01

    Although antibiotics have significantly improved human health and life expectancy, their disruption of the existing microbiota has been linked to significant side effects such as antibiotic-associated diarrhea, pseudomembranous colitis, and increased susceptibility to subsequent disease. By using antibiotics to break colonization resistance against Clostridium, Salmonella, and Citrobacter species, researchers are now exploring mechanisms for microbiota-mediated modulation against pathogenic infection, revealing potential roles for different phyla and family members as well as microbiota-liberated sugars, hormones, and short-chain fatty acids in regulating pathogenicity. Furthermore, connections are now being made between microbiota dysbiosis and a variety of different diseases such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, atopy, and obesity. Future advances in the rapidly developing field of microbial bioinformatics will enable researchers to further characterize the mechanisms of microbiota modulation of disease and potentially identify novel therapeutics against disease.

  18. Human heart disease : lessons from human pluripotent stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Giacomelli, E.; Mummery, C.L.; Bellin, M.

    2017-01-01

    Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current

  19. Interconnectivity of human cellular metabolism and disease prevalence

    International Nuclear Information System (INIS)

    Lee, Deok-Sun

    2010-01-01

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease–gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery

  20. Lipid metabolism in peroxisomes in relation to human disease

    NARCIS (Netherlands)

    Wanders, R. J.; Tager, J. M.

    1998-01-01

    Peroxisomes were long believed to play only a minor role in cellular metabolism but it is now clear that they catalyze a number of important functions. The importance of peroxisomes in humans is stressed by the existence of a group of genetic diseases in man in which one or more peroxisomal

  1. Gene therapy in nonhuman primate models of human autoimmune disease

    NARCIS (Netherlands)

    t'Hart, B. A.; Vervoordeldonk, M.; Heeney, J. L.; Tak, P. P.

    2003-01-01

    Before autoimmune diseases in humans can be treated with gene therapy, the safety and efficacy of the used vectors must be tested in valid experimental models. Monkeys, such as the rhesus macaque or the common marmoset, provide such models. This publication reviews the state of the art in monkey

  2. [Leprosy, a pillar of human genetics of infectious diseases].

    Science.gov (United States)

    Gaschignard, J; Scurr, E; Alcaïs, A

    2013-06-01

    Despite a natural reservoir of Mycobacterium leprae limited to humans and free availability of an effective antibiotic treatment, more than 200,000 people develop leprosy each year. This disease remains a major cause of disability and social stigma worldwide. The cause of this constant incidence is currently unknown and indicates that important aspects of the complex relationship between the pathogen and its human host remain to be discovered. An important contribution of host genetics to susceptibility to leprosy has long been suggested to account for the considerable variability between individuals sustainably exposed to M. leprae. Given the inability to cultivate M. leprae in vitro and in the absence of relevant animal model, genetic epidemiology is the main strategy used to identify the genes and, consequently, the immunological pathways involved in protective immunity to M. leprae. Recent genome-wide studies have identified new pathophysiological pathways which importance is only beginning to be understood. In addition, the prism of human genetics placed leprosy at the crossroads of other common diseases such as Crohn's disease, asthma or myocardial infarction. Therefore, novel lights on the pathogenesis of many common diseases could eventually emerge from the detailed understanding of a disease of the shadows. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. James Cronin, CP Violation, and the Pierre Auger Observatory

    Science.gov (United States)

    dropdown arrow Site Map A-Z Index Menu Synopsis James Cronin, CP Violation and the Pierre Auger Observatory matter over antimatter."1 "The experiment uncovered the CP [charge-parity] violation, or a with Additional Information Additional information about James Cronin and the charge-parity (CP

  4. James Madison High School. A Curriculum for American Students.

    Science.gov (United States)

    Bennett, William J.

    This document presents the Secretary of Education's personal concept of a sound secondary school core curriculum. It is called "James Madison High School" in honor of President James Madison and his strong views that the people, in order to govern properly, must arm themselves with knowledge. The theoretical curriculum consists of four…

  5. James Hillman: Toward a poetic psychology.

    Science.gov (United States)

    Avens, R

    1980-09-01

    InThe Dream and the Underworld James Hillman continues to deepen and to refine Jung's recovery of the spontaneous image-making of the soul. Hillman's contribution lies in his "imaginai reduction"-relating of images to their archetypal background in Greek mythology. Myth is seen as the maker of the psyche, and, in turn, the soul-making ispoesis-a return to the imaginal and poetic basis of consciousness. Dreams, understood poetically, are neither messages to be deciphered and used for the benefit of the rational ego (Freud) nor compensatory to the ego (Jung); they are complete in themselves and must be allowed to speak for themselves. Hillman also sees dreams as initiations into the underworld of death-the other side of life where our imaginal substance is unobstructed by the literal and dualistic standpoints of the dayworld.

  6. Single-Domain Antibodies As Therapeutics against Human Viral Diseases

    Directory of Open Access Journals (Sweden)

    Yanling Wu

    2017-12-01

    Full Text Available In full-size formats, monoclonal antibodies have been highly successful as therapeutics against cancer and immune diseases. However, their large size leads to inaccessibility of some epitopes and relatively high production costs. As an alternative, single-domain antibodies (sdAbs offer special advantages compared to full-size antibodies, including smaller size, larger number of accessible epitopes, relatively low production costs and improved robustness. Currently, sdAbs are being developed against a number of viruses, including human immunodeficiency virus-1 (HIV-1, influenza viruses, hepatitis C virus (HCV, respiratory syncytial virus (RSV, and enteric viruses. Although sdAbs are very potent inhibitors of viral infections, no sdAbs have been approved for clinical use against virial infection or any other diseases. In this review, we discuss the current state of research on sdAbs against viruses and their potential as therapeutics against human viral diseases.

  7. Leveraging human-centered design in chronic disease prevention.

    Science.gov (United States)

    Matheson, Gordon O; Pacione, Chris; Shultz, Rebecca K; Klügl, Martin

    2015-04-01

    Bridging the knowing-doing gap in the prevention of chronic disease requires deep appreciation and understanding of the complexities inherent in behavioral change. Strategies that have relied exclusively on the implementation of evidence-based data have not yielded the desired progress. The tools of human-centered design, used in conjunction with evidence-based data, hold much promise in providing an optimal approach for advancing disease prevention efforts. Directing the focus toward wide-scale education and application of human-centered design techniques among healthcare professionals will rapidly multiply their effective ability to bring the kind of substantial results in disease prevention that have eluded the healthcare industry for decades. This, in turn, would increase the likelihood of prevention by design. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Human genetics of infectious diseases: a unified theory

    Science.gov (United States)

    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

    Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

  9. Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

    Science.gov (United States)

    Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

    2016-01-01

    Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Human endogenous retroviruses and chosen disease parameters in morphea

    Science.gov (United States)

    Dańczak-Pazdrowska, Aleksandra; Szramka-Pawlak, Beata; Żaba, Ryszard; Osmola-Mańkowska, Agnieszka; Silny, Wojciech

    2017-01-01

    Introduction Morphea (localized scleroderma) is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV) are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. Aim In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index). Material and methods Real-time polymerase chain reaction (PCR) targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC) and skin biopsies. Results In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01). Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. Conclusions Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing. PMID:28261031

  11. Human endogenous retroviruses and chosen disease parameters in morphea

    Directory of Open Access Journals (Sweden)

    Michał J. Kowalczyk

    2017-02-01

    Full Text Available Introduction: Morphea (localized scleroderma is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. Aim: In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index. Material and methods: Real-time polymerase chain reaction (PCR targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC and skin biopsies. Results: In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01. Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. Conclusions : Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing.

  12. A framework for annotating human genome in disease context.

    Science.gov (United States)

    Xu, Wei; Wang, Huisong; Cheng, Wenqing; Fu, Dong; Xia, Tian; Kibbe, Warren A; Lin, Simon M

    2012-01-01

    Identification of gene-disease association is crucial to understanding disease mechanism. A rapid increase in biomedical literatures, led by advances of genome-scale technologies, poses challenge for manually-curated-based annotation databases to characterize gene-disease associations effectively and timely. We propose an automatic method-The Disease Ontology Annotation Framework (DOAF) to provide a comprehensive annotation of the human genome using the computable Disease Ontology (DO), the NCBO Annotator service and NCBI Gene Reference Into Function (GeneRIF). DOAF can keep the resulting knowledgebase current by periodically executing automatic pipeline to re-annotate the human genome using the latest DO and GeneRIF releases at any frequency such as daily or monthly. Further, DOAF provides a computable and programmable environment which enables large-scale and integrative analysis by working with external analytic software or online service platforms. A user-friendly web interface (doa.nubic.northwestern.edu) is implemented to allow users to efficiently query, download, and view disease annotations and the underlying evidences.

  13. James Wallbank (Redundant Technology Initiative) (RTI) / James Wallbank ; interv. Tilman Baumgärtel

    Index Scriptorium Estoniae

    Wallbank, James

    2006-01-01

    James Wallbank (sünd. 1966) on RTI (Aegunud Tehnoloogia Initsiatiiv), mis hoiab alates 2000. aastast käigus Interneti-kohvikut "Access Space") Sheffieldis, rajaja. J. Wallbank 6. 10. 2000 tehtud intervjuus RTI-st, mis kasutab oma installatsioonides, skulptuurides ja teistes madaltehnoloogilistes teostes vanu arvuteid, installatsioonist näitusel "net_condition" Karlssruhe Kunsti- ja Meediatehnoloogia Keskuses (1999), tööst "Network Low Tech Video Wall" (2000) ja muust

  14. Differential overexpression of SERPINA3 in human prion diseases.

    Science.gov (United States)

    Vanni, S; Moda, F; Zattoni, M; Bistaffa, E; De Cecco, E; Rossi, M; Giaccone, G; Tagliavini, F; Haïk, S; Deslys, J P; Zanusso, G; Ironside, J W; Ferrer, I; Kovacs, G G; Legname, G

    2017-11-15

    Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.

  15. Human anthrax as a re-emerging disease.

    Science.gov (United States)

    Doganay, Mehmet; Demiraslan, Hayati

    2015-01-01

    Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

  16. Mobile technologies for disease surveillance in humans and animals.

    Science.gov (United States)

    Mwabukusi, Mpoki; Karimuribo, Esron D; Rweyemamu, Mark M; Beda, Eric

    2014-04-23

    A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara), Burundi (Muyinga) and Zambia (Kazungula and Sesheke). Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server-client model. Smart phones running the Android operating system (minimum required version: Android 1.6), and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing timely response in rural remote areas of

  17. The human oral metaproteome reveals potential biomarkers for caries disease

    DEFF Research Database (Denmark)

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea

    2015-01-01

    metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status......Tooth decay is considered the most prevalent human disease worldwide. We present the first metaproteomic study of the oral biofilm, using different mass spectrometry approaches that have allowed us to quantify individual peptides in healthy and caries-bearing individuals. A total of 7771 bacterial...... and 853 human proteins were identified in 17 individuals, which provide the first available protein repertoire of human dental plaque. Actinomyces and Coryneybacterium represent a large proportion of the protein activity followed by Rothia and Streptococcus. Those four genera account for 60-90% of total...

  18. Human Parasitic Diseases in Bulgaria in Between 2013-2014

    Science.gov (United States)

    Rainova, Iskra; Harizanov, Rumen; Kaftandjiev, Iskren; Tsvetkova, Nina; Mikov, Ognyan; Kaneva, Eleonora

    2018-01-01

    Background: In Bulgaria, more than 20 autochthonous human parasitic infections have been described and some of them are widespread. Over 50 imported protozoan and helminthic infections represent diagnostic and therapeutic challenges and pose epidemiological risks due to the possibility of local transmission. Aims: To establish the distribution of autochthonous and imported parasitic diseases among the population of the country over a 2-year period (2013-2014) and to evaluate their significance in the public health system. Study Design: Cross sectional study. Methods: We used the annual reports by regional health inspectorates and data from the National Reference Laboratory at the National Centre of Infectious and Parasitic Diseases on all individuals infected with parasitic diseases in the country. Prevalence was calculated for parasitic diseases with few or absent clinical manifestations (oligosymptomatic or asymptomatic infections). Incidence per 100.000 was calculated for diseases with an overt clinical picture or those that required hospitalisation and specialised medical interventions (e.g. surgery). Results: During the research period, parasitological studies were conducted on 1441.244 persons, and parasitic infections were diagnosed in 22.039 individuals. Distribution of various parasitic pathogens among the population displayed statistically significant differences in prevalence for some intestinal parasites (enterobiasis 0.81%, giardiasis 0.34% and blastocystosis 0.22%). For certain zoonotic diseases such as cystic echinococcosis (average incidence of 3.99 per 100.000) and trichinellosis (average incidence of 0.8 per 100.000), the incidence exceeds several times the annual incidence recorded in the European Union. Conclusion: Parasitic diseases still pose a substantial problem with social and medical impacts on the residents of our country. Improved efficiency regarding autochthonous and imported parasitic diseases is essential in providing the public

  19. Credit scores, cardiovascular disease risk, and human capital.

    Science.gov (United States)

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

    2014-12-02

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

  20. Limits to human enhancement: nature, disease, therapy or betterment?

    Science.gov (United States)

    Hofmann, Bjørn

    2017-10-10

    New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

  1. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  2. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    OpenAIRE

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

  3. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...

  4. A Novel Human Body Area Network for Brain Diseases Analysis.

    Science.gov (United States)

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

  5. Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

    Science.gov (United States)

    Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function. © 2015 John Wiley & Sons Ltd.

  6. Under the lash: Demodex mites in human diseases.

    Science.gov (United States)

    Lacey, Noreen; Kavanagh, Kevin; Tseng, Scheffer C G

    2009-08-01

    Demodex mites, class Arachnida and subclass Acarina, are elongated mites with clear cephalothorax and abdomens, the former with four pairs of legs. There are more than 100 species of Demodex mite, many of which are obligatory commensals of the pilosebaceous unit of mammals including cats, dogs, sheep, cattle, pigs, goats, deer, bats, hamsters, rats and mice. Among them, Demodex canis, which is found ubiquitously in dogs, is the most documented and investigated. In excessive numbers D. canis causes the inflammatory disease termed demodicosis (demodectic mange, follicular mange or red mange), which is more common in purebred dogs and has a hereditary predisposition in breeding kennels1. Two distinct Demodex species have been confirmed as the most common ectoparasite in man. The larger Demodex folliculorum, about 0.3-0.4 mm long, is primarily found as a cluster in the hair follicle (Figure 1a), while the smaller Demodex brevis, about 0.2-0.3 mm long with a spindle shape and stubby legs, resides solitarily in the sebaceous gland (Figure 1b). These two species are also ubiquitously found in all human races without gender preference. The pathogenic role of Demodex mites in veterinary medicine is not as greatly disputed as in human diseases. In this article, we review the key literature and our joint research experience regarding the pathogenic potential of these two mites in causing inflammatory diseases of human skin and eye. We hope that the evidence summarized herein will invite readers to take a different look at the life of Demodex mites in several common human diseases.

  7. Does biodiversity protect humans against infectious disease? Reply

    Science.gov (United States)

    Wood, Chelsea L.; Lafferty, Kevin D.; DeLeo, Giulio; Young, Hillary S.; Hudson, Peter J.; Kuris, Armand M.

    2016-01-01

    The dilution effect is the sort of idea that everyone wants to be true. If nature protects humans against infectious disease, imagine the implications: nature's value could be tallied in terms of human suffering avoided. This makes a potent argument for conservation, convincing even to those who would otherwise be disinclined to support conservation initiatives. The appeal of the dilution effect has been recognized by others: “the desire to make the case for conservation has led to broad claims regarding the benefits of nature conservation for human health” (Bauch et al. 2015). Randolph and Dobson (2012) were among the first to critique these claims, making the case that promotion of conservation to reduce Lyme disease risk, although well intentioned, was flawed. Along with Randolph and Dobson's critique, there have been several calls for a more nuanced scientific assessment of the relationship between biodiversity and disease transmission (Dunn 2010, Salkeld et al. 2013, Wood and Lafferty 2013, Young et al. 2013). In response, supporters of the dilution effect have instead increased the scope of their generalizations with review papers, press releases, and, like Levi et al. (2015), letters. These responses have been successful; it is not uncommon to read papers that repeat the assertion that biodiversity generally interferes with disease transmission and that conservation will therefore generally benefit human health. Here, we explain how Levi et al. (2015) and other, similar commentaries use selective interpretation and shifting definitions to argue for the generality of the dilution effect hypothesis.

  8. Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

    Science.gov (United States)

    Jang, Jiho; Yoo, Jeong-Eun; Lee, Jeong-Ah; Lee, Dongjin R; Kim, Ji Young; Huh, Yong Jun; Kim, Dae-Sung; Park, Chul-Yong; Hwang, Dong-Youn; Kim, Han-Soo; Kang, Hoon-Chul; Kim, Dong-Wook

    2012-03-31

    The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

  9. Immunomodulatory activity of interleukin-27 in human chronic periapical diseases.

    Science.gov (United States)

    Li, Juan; Wang, Rong; Huang, Shi-Guang

    2017-01-01

    This study aims to observe expression of IL-27 on different cells in periapical tissues of different types of human chronic periapical diseases. Periapical tissue specimens of 60 donors, including healthy control (n=20), periapical granuloma group (n=20) and radicular cysts group (n=20), were fixed in 10% buffered formalin, stained with hematoxylin and eosin for histopathology. Then specimens were stained with double- immuno-fluorescence assay for identification of IL-27-tryptase (mast cells, MCs), IL-27-CD14 (mononuclear phagocyte cells, MPs) and IL-27-CD31 (endothelial cells, ECs) double-positive cells in periapical tissues. The results indicated that compared with healthy control, the densities (cells/mm 2 ) of IL-27-tryptase, IL-27-CD14 and IL-27-CD31 double-positive cells were significantly increased in human chronic periapical diseases (periapical granuloma group and radicular cysts group) ( P cysts group was significantly higher than those in periapical granuloma group ( P periapical granuloma group had no significant difference with those in radicular cysts group ( P =0.170 and 0.138, respectively). IL-27-CD14 double positive cells density achieved to peak among three cell groups in radicular cysts groups. In conclusion, IL-27 expressed in MCs, MPs and ECs of human chronic periapical diseases with different degrees. IL-27-tryptase double-positive cells may participate in pathogenic mechanism of chronic periapical diseases, especially for formation of fibrous in periapical cysts. IL-27-CD14 and IL-27-CD31 double-positive cells may participate in immunologic response to resist periapical infection, and they may play an dual role in pathogenesis and localization of periapical diseases.

  10. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    International Nuclear Information System (INIS)

    Ejima, Yosuke

    1988-01-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G 0 or G 1 phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases. (author)

  11. DNA repair processes and their impairment in some human diseases

    International Nuclear Information System (INIS)

    Cleaver, J.E.

    1977-01-01

    Some human diseases show enhanced sensitivity to the action of environmental mutagens, and among these several are known which are defective in the repair of damaged DNA. Xeroderma pigmentosum (XP) is mainly defective in excision repair of a large variety of damaged DNA bases caused by ultraviolet light and chemical mutagens. XP involves at least 6 distinct groups, some of which may lack cofactors required for excising damage from chromatin. As a result of these defects the sensitivity of XP cells to many mutagens is increased 5- to 10-fold. Ataxia telangiectasia and Fanconi's anemia may similarly involve defects in repair of certain DNA base damage or cross-links, respectively. But most of these and other mutagen-sensitive diseases only show increases of about 2-fold in sensitivity to mutagens, and the biochemical defects in the diseases may be more complex and less directly involved in DNA repair than in XP. (Auth.)

  12. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Ejima, Yosuke; Ikushima, Takaji (ed.)

    1988-07-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G/sub 0/ or G/sub 1/ phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases.

  13. HUMAN PAPILLOMA VIRUS. PREVENTION OF HPV-ASSOCIATED DISEASES

    Directory of Open Access Journals (Sweden)

    F. C. Shakhtakhtinskaya

    2015-01-01

    Full Text Available High prevalence of sexually transmitted diseases among the population attracts attention of specialists in all countries due to frequent development of complications resulting in reproductive dysfunction. The article presents one of the urgent issues of modern medicine — papillomavirus infection, which is the most common sexually transmitted disease. 70–80% of the sexually active persons contract human papilloma virus at one point. HPV induces a broad range of oncological reproductive diseases, including cervical, vulvar, vaginal and anal cancer and anogenital condylomae, which are observed both in men and women. The only reliable method of preventing papillomavirus infection is vaccination. The authors present new data on the use of the quadrivalent vaccine, including a new immunization pattern for 9–14-years-old girls.

  14. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B

    1989-01-01

    cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi......Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes......'s sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies....

  15. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    Science.gov (United States)

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

  16. Proteomic approach in human health and disease: Preventive and cure studies

    Directory of Open Access Journals (Sweden)

    Khaled MM Koriem

    2018-01-01

    Full Text Available Proteomic is a branch of science that deals with various numbers of proteins where proteins are essential human constituents. Proteomic has a lot of functions inside the human and animal living organisms. This review helps to make a thought on the importance of proteomic application in human health and disease with special reference to preventive and cure studies. The human health can be divided into physical and mental health. The physical health relates to keeping human body state in a good health and to nutritional type and environmental factors. The mental health correlates to human psychological state. The main factors that affect the status of human health are human diet, exercise and sleep. The healthy diet is very important and needs to maintain the human health. The training program exercise improves human fitness and overall health and wellness. The sleep is a vital factor to sustain the human health. The human disease indicates abnormal human condition which influences the specific human part or the whole human body. There are external and internal factors which induce human disease. The external factors include pathogens while internal factors include allergies and autoimmunity. There are 4 principle types of human diseases: (1 infectious disease, (2 deficiency disease, (3 genetic disease and (4 physiological disease. There are many and various external microbes' factors that induce human infectious disease and these agents include viruses, bacteria, fungi and protozoa. The lack of necessary and vital dietary rudiments such as vitamins and minerals is the main cause of human deficiency disease. The genetic disease is initiated by hereditary disturbances that occur in the human genetic map. The physiological disease occurs when the normal human function body is affected due to human organs become malfunction. In conclusion, proteomic plays a vital and significant role in human health and disease.

  17. DRUMS: a human disease related unique gene mutation search engine.

    Science.gov (United States)

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. © 2011 Wiley-Liss, Inc.

  18. IgY antibodies in human nutrition for disease prevention.

    Science.gov (United States)

    Müller, Sandra; Schubert, Andreas; Zajac, Julia; Dyck, Terry; Oelkrug, Christopher

    2015-10-20

    Oral administration of preformed specific antibodies is an attractive approach against infections of the digestive system in humans and animals in times of increasing antibiotic resistances. Previous studies showed a positive effect of egg yolk IgY antibodies on bacterial intoxications in animals and humans. Immunization of chickens with specific antigens offers the possibility to create various forms of antibodies. Research shows that orally applied IgY's isolated from egg yolks can passively cure or prevent diseases of the digestive system. The use of these alternative therapeutic drugs provides further advantages: (1) The production of IgY's is a non-invasive alternative to current methods; (2) The keeping of chickens is inexpensive; (3) The animals are easy to handle; (4) It avoids repetitive bleeding of laboratory animals; (5) It is also very cost effective regarding the high IgY concentration within the egg yolk. Novel targets of these antigen specific antibodies are Helicobacter pylori and also molecules involved in signaling pathways in gastric cancer. Furthermore, also dental caries causing bacteria like Streptococcus mutans or opportunistic Pseudomonas aeruginosa in cystic fibrosis patients are possible targets. Therefore, IgY's included in food for human consumption may be able to prevent or cure human diseases.

  19. James Joyce's Ulysses: The Search for Value

    Directory of Open Access Journals (Sweden)

    Aouda Aljohani

    2014-01-01

    Full Text Available Two chapters, "Scylla and Charybdis" and "Penelope," in James Joyce's Ulysses are crucial to an understanding of the novel as a whole. "Scylla and Charybdis" stands midway in the novel, the ninth of eighteen chapters, and is designed to serve as a kind of exegesis of the writer's methods and intentions. An analysis of that chapter helps to explain the meaning of the controversial final chapter, "Penelope," and to clarify its thematic and stylistic relation to the text as a whole. Ulysses is the story of a quest, actually of many quests that all coalesce into a single goal: the search for value in a modern world that is somehow diminished and constructed in comparison with the Homeric world where mortals strode the universe in company with gods and goddesses. How, in this dwarfed setting, can men and women redefine heroism in secular humanistic terms relevant to twentieth-century life? Almost by definition a quest narrative culminates in the attainment of the goal or in the potential for its attainment; Joyce's Ulysses affirms this possibility in "Penelope."

  20. James Moores Ball: Ophthalmologist, medical historian, bibliophile.

    Science.gov (United States)

    Feibel, Robert M

    2016-08-01

    James Moores Ball (1862-1929) was an ophthalmologist in St. Louis, Missouri, who excelled as a medical historian and collector of rare and historic books about the history of anatomy. During his lifetime, he was best known as the author of a comprehensive, authoritative, and popular textbook titled Modern Ophthalmology First published in 1904, there were five further editions. Ball was very interested in the history of anatomy and wrote two books on this subject, the first being a biography of Andreas Vesalius, one of the earliest in English, and the second a history of the resurrection men or grave robbers who sold corpses to professors of anatomy and surgery for teaching purposes. His legacy today is the 470 volumes of his personal library, which are now in the Archives and Rare Books department of the Becker Medical Library of the Washington University School of Medicine. These texts are one of their major collections, concentrating on the history of anatomy, beginning with a first edition of Vesalius's De Humani Corporis Fabrica and holding many important and beautiful landmark volumes of anatomical atlases. © The Author(s) 2016.

  1. The James Webb Space Telescope Mission

    Science.gov (United States)

    Sonneborn, George

    2010-01-01

    The James Webb Space Telescope (JWST) is a large aperture, cryogenic, infrared-optimized space observatory under development by NASA for launch in 2014. The European and Canadian Space Agencies are mission partners. JWST will find and study the first galaxies that formed in the early universe, peer through dusty clouds to see AGN environments and stars forming planetary systems at high spatial resolution. The breakthrough capabilities of JWST will enable new studies of star formation and evolution in the Milky Way, including the Galactic Center, nearby galaxies, and the early universe. JWST's instruments are designed to work primarily in the infrared range of 1 - 28 microns, with some capability in the visible. JWST will have a segmented primary mirror, approximately 6.5 meters in diameter, and will be diffraction-limited at wavelength of 2 microns (0.1 arcsec resolution). The JWST observatory will be placed in a L2 orbit by an Ariane 5 launch vehicle provided by ESA. The observatory is designed for a 5-year prime science mission, with propellant for 10 years of science operations. The instruments will provide broad- and narrow-band imaging, coronography, and multi-object and integral-field spectroscopy (spectral resolution of 100 to 3,000) across the 1 - 28 micron wavelength range. Science and mission operations will be conducted from the Space Telescope Science Institute in Baltimore, Maryland.

  2. The "Very Cool" James Webb Space Telescope!

    Science.gov (United States)

    Teague, Peter J. B.

    2018-01-01

    For over twenty years, scientists, engineers, technicians, and other personnel have been working on the next generation space telescope. As a partnership between NASA (National Aeronautics and Space Administration), CSA (Canadian Space Agency), and ESA (European Space Angency), the James Webb Space Telescope will complement the previous research performed by the Hubble by utilizing a larger primary mirror, which will also be optimized for infrared wavelengths. This combination will allow JWST to collect data and take images of light having traveled over 13.7 billion light years. This presentation will focus on the mission, as well as the contamination control challenges during the integration and testing in the NASA Goddard Spacecraft Systems Development and Integration Facility (SSDIF), one of the largest cleanrooms in the world. Additional information will be presented regarding space simulation testing down to a cool 20 degrees Kelvin [-424 degrees Fahrenheit] that will occur at Johnson Space Center in Houston, TX, and more testing and integration to happen at Northrop Grumman Corp., in Redondo Beach, CA. Launch of the JWST is currently scheduled for the spring of 2019 at Ariane Spaceport in French Guiana, South America.

  3. James F. T. Bugental (1915-2008).

    Science.gov (United States)

    Schneider, Kirk J; Greening, Tom

    2009-01-01

    James F. T. Bugental died peacefully at age 92 at his Petaluma, California, home on September 18, 2008. Jim was a leading psychotherapist and a founding father, with Abraham Maslow and others, of humanistic psychology, or the "third force" (in contrast to psychoanalysis and behaviorism). Jim was also the creator, along with Rollo May, of existential-humanistic psychotherapy. Jim was born in Fort Wayne, Indiana, on Christmas Day in 1915. Jim earned his doctorate in 1948 from Ohio State University, where he was influenced by Victor Raimy and George Kelly. After a brief time on the University of California, Los Angeles (UCLA) faculty in psychology, Jim resigned in 1953 to found the first group practice of psychotherapy, Psychological Service Associates, with Alvin Lasko. With Abraham Maslow and others, Jim was a cofounder of the Journal of Humanistic Psychology (JHP) and the Association for Humanistic Psychology in 1961. Jim also wrote many books on the topic of psychotherapy during his lifetime. Jim was a great and bold spirit--his many writings and teachings are cherished today widely, and the field of psychology is much richer for his efforts. 2009 APA, all rights reserved

  4. Watching Time: James Baldwin and Malcolm X

    Directory of Open Access Journals (Sweden)

    Mikko Tuhkanen

    2016-12-01

    Full Text Available Taking its cue from recent scholarly work on the concept of time in African American literature, this essay argues that, while both James Baldwin and Malcolm X refuse gradualism and insist on “the now” as the moment of civil rights’ fulfillment, Baldwin also remains troubled by the narrowness assumed by a life, politics, or ethics limited to the present moment. In his engagement with Malcolm’s life and legacy—most notably in One Day, When I Was Lost, his screen adaptation of Malcolm’s autobiography—he works toward a temporal mode that would be both punctual and expansive. What he proposes as the operative time of chronoethics is an “untimely now”: he seeks to replace Malcolm’s unyielding punctuality with a different nowness, one that rejects both calls for “patience,” endemic to any politics that rests on the Enlightenment notion of “perfectibility,” and the breathless urgency that prevents the subject from seeing anything beyond the oppressive system he wants overthrown. Both thinkers find the promise of such untimeliness in their sojourns beyond the United States.

  5. James Henry Greathead en die Londense Moltrein

    Directory of Open Access Journals (Sweden)

    Laurence Wright

    2017-07-01

    Full Text Available Die artikel ondersoek die oorsprong en vroeë geskiedenis van die toestel genaamd die ‘Greathead Skild’, ‘n belangrike nuwigheid in Viktoriaanse ingenieurwetenskap, wat van deurslaggewende belang was in die konstruksie van die Londense Moltrein. Die doel is om die basis te ontleed waarop, baie jare later, ‘n Suid-Afrikaanse ingenieur wye openbare erkenning in die vorm van ‘n standbeeld vir die ‘ontwerp’ van die Skild geniet het. Uit die perspektief van kulturele studies beskou, hoe moet ons uitvinding verstaan, gegewe dat ander briljante ingenieurs ook betrokke was? Hierdie vraag word ontleed met die gebruik van die konsep ‘extelligence’ (Stewart and Cohen 1997, in samehang met ander kontemporêre en geskiedkundige weergawes, insluitend Greathead se eie rekord van sy prestasies in die verrigtinge van die Instituut van Siviele Ingenieurs en voorgelê in The City and South London Railway (1896, onder redaksie van James Forrest. Hierdie artikel is die eerste keer as referaat aangebied by die konferensie oor ‘Nuuthede en Innovasie in die Negentiende Eeu’ aan die Noordwes-Universiteit, Mei 2016.

  6. Imaging neuroreceptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.; Dannals, R.F.; Frost, J.J.

    1985-01-01

    For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human brain in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, and glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On 25 May 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 N-methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine-2 receptors than in serotonin-2 receptors. Preliminary studies of patients with neuropsychiatric disorders suggest that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits a quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. (author)

  7. Drosophila as an In Vivo Model for Human Neurodegenerative Disease

    Science.gov (United States)

    McGurk, Leeanne; Berson, Amit; Bonini, Nancy M.

    2015-01-01

    With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. PMID:26447127

  8. Global Considerations in Human Immunodeficiency Virus-Associated Respiratory Disease.

    Science.gov (United States)

    Rylance, Jamie; Meghji, Jamilah; Miller, Robert F; Ferrand, Rashida A

    2016-04-01

    Respiratory tract infection, particularly tuberculosis, is a major cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Antiretroviral therapy (ART) has resulted in a dramatic increase in survival, although coverage of HIV treatment remains low in many parts of the world. There is a concurrent growing burden of chronic noninfectious respiratory disease as a result of increased survival. Many risk factors associated with the development of respiratory disease, such as cigarette smoking and intravenous drug use, are overrepresented among people living with HIV. In addition, there is emerging evidence that HIV infection may directly cause or accelerate the course of chronic lung disease. This review summarizes the clinical spectrum and epidemiology of respiratory tract infections and noninfectious pulmonary pathologies, and factors that explain the global variation in HIV-associated respiratory disease. The potential for enhancing diagnoses of noninfective chronic conditions through the use of clinical algorithms is discussed. We also consider issues in assessment and management of HIV-related respiratory disease in view of the increasing global scale up of ART. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Kuidas kõrgemale ohvitserile ettekannet teha / James Stavridis

    Index Scriptorium Estoniae

    Stavridis, James, 1955-

    2013-01-01

    Endine NATO Euroopa liitlasvägede ülemjuhataja jagab nõuandeid mõjusa ja konstruktiivse ettekande kirjutamiseks ja selle esitlemiseks. Lisatud foto, kus kujutatud James Stavridise autasustamist president Toomas Hendrik Ilvese poolt

  10. NASA 3D Models: James Webb Space Telescope

    Data.gov (United States)

    National Aeronautics and Space Administration — The James Webb Space Telescope (JWST) will be a large infrared telescope with a 6.5-meter primary mirror. The project is working to a 2018 launch date. The JWST will...

  11. Young James Madison: His Character and Civic Values.

    Science.gov (United States)

    Bennett, William J.

    1987-01-01

    Examines the life of James Madison, Founding Father and "theoretic statesman." Focuses specifically on Madison's education and character, his friendship with Thomas Jefferson, and his civic legacy: a selfless devotion to republican government and union. (JDH)

  12. Human Gut Microbiota: Toward an Ecology of Disease

    Directory of Open Access Journals (Sweden)

    Susannah Selber-Hnatiw

    2017-07-01

    Full Text Available Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.

  13. Human Gut Microbiota: Toward an Ecology of Disease

    Science.gov (United States)

    Selber-Hnatiw, Susannah; Rukundo, Belise; Ahmadi, Masoumeh; Akoubi, Hayfa; Al-Bizri, Hend; Aliu, Adelekan F.; Ambeaghen, Tanyi U.; Avetisyan, Lilit; Bahar, Irmak; Baird, Alexandra; Begum, Fatema; Ben Soussan, Hélène; Blondeau-Éthier, Virginie; Bordaries, Roxane; Bramwell, Helene; Briggs, Alicia; Bui, Richard; Carnevale, Matthew; Chancharoen, Marisa; Chevassus, Talia; Choi, Jin H.; Coulombe, Karyne; Couvrette, Florence; D'Abreau, Samantha; Davies, Meghan; Desbiens, Marie-Pier; Di Maulo, Tamara; Di Paolo, Sean-Anthony; Do Ponte, Sabrina; dos Santos Ribeiro, Priscyla; Dubuc-Kanary, Laure-Anne; Duncan, Paola K.; Dupuis, Frédérique; El-Nounou, Sara; Eyangos, Christina N.; Ferguson, Natasha K.; Flores-Chinchilla, Nancy R.; Fotakis, Tanya; Gado Oumarou H D, Mariam; Georgiev, Metodi; Ghiassy, Seyedehnazanin; Glibetic, Natalija; Grégoire Bouchard, Julien; Hassan, Tazkia; Huseen, Iman; Ibuna Quilatan, Marlon-Francis; Iozzo, Tania; Islam, Safina; Jaunky, Dilan B.; Jeyasegaram, Aniththa; Johnston, Marc-André; Kahler, Matthew R.; Kaler, Kiranpreet; Kamani, Cedric; Karimian Rad, Hessam; Konidis, Elisavet; Konieczny, Filip; Kurianowicz, Sandra; Lamothe, Philippe; Legros, Karina; Leroux, Sebastien; Li, Jun; Lozano Rodriguez, Monica E.; Luponio-Yoffe, Sean; Maalouf, Yara; Mantha, Jessica; McCormick, Melissa; Mondragon, Pamela; Narayana, Thivaedee; Neretin, Elizaveta; Nguyen, Thi T. T.; Niu, Ian; Nkemazem, Romeo B.; O'Donovan, Martin; Oueis, Matthew; Paquette, Stevens; Patel, Nehal; Pecsi, Emily; Peters, Jackie; Pettorelli, Annie; Poirier, Cassandra; Pompa, Victoria R.; Rajen, Harshvardhan; Ralph, Reginald-Olivier; Rosales-Vasquez, Josué; Rubinshtein, Daria; Sakr, Surya; Sebai, Mohammad S.; Serravalle, Lisa; Sidibe, Fily; Sinnathurai, Ahnjana; Soho, Dominique; Sundarakrishnan, Adithi; Svistkova, Veronika; Ugbeye, Tsolaye E.; Vasconcelos, Megan S.; Vincelli, Michael; Voitovich, Olga; Vrabel, Pamela; Wang, Lu; Wasfi, Maryse; Zha, Cong Y.; Gamberi, Chiara

    2017-01-01

    Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics. PMID:28769880

  14. Mobile technologies for disease surveillance in humans and animals

    Directory of Open Access Journals (Sweden)

    Mpoki Mwabukusi

    2014-04-01

    Full Text Available A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara, Burundi (Muyinga and Zambia (Kazungula and Sesheke. Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server–client model. Smart phones running the Android operating system (minimum required version: Android 1.6, and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing

  15. Functional modules, mutational load and human genetic disease.

    Science.gov (United States)

    Zaghloul, Norann A; Katsanis, Nicholas

    2010-04-01

    The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Role of Lactobacillus reuteri in Human Health and Diseases

    Directory of Open Access Journals (Sweden)

    Qinghui Mu

    2018-04-01

    Full Text Available Lactobacillus reuteri (L. reuteri is a well-studied probiotic bacterium that can colonize a large number of mammals. In humans, L. reuteri is found in different body sites, including the gastrointestinal tract, urinary tract, skin, and breast milk. The abundance of L. reuteri varies among different individuals. Several beneficial effects of L. reuteri have been noted. First, L. reuteri can produce antimicrobial molecules, such as organic acids, ethanol, and reuterin. Due to its antimicrobial activity, L. reuteri is able to inhibit the colonization of pathogenic microbes and remodel the commensal microbiota composition in the host. Second, L. reuteri can benefit the host immune system. For instance, some L. reuteri strains can reduce the production of pro-inflammatory cytokines while promoting regulatory T cell development and function. Third, bearing the ability to strengthen the intestinal barrier, the colonization of L. reuteri may decrease the microbial translocation from the gut lumen to the tissues. Microbial translocation across the intestinal epithelium has been hypothesized as an initiator of inflammation. Therefore, inflammatory diseases, including those located in the gut as well as in remote tissues, may be ameliorated by increasing the colonization of L. reuteri. Notably, the decrease in the abundance of L. reuteri in humans in the past decades is correlated with an increase in the incidences of inflammatory diseases over the same period of time. Direct supplementation or prebiotic modulation of L. reuteri may be an attractive preventive and/or therapeutic avenue against inflammatory diseases.

  17. Transcriptome Profiling in Human Diseases: New Advances and Perspectives

    Directory of Open Access Journals (Sweden)

    Amelia Casamassimi

    2017-07-01

    Full Text Available In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements and TCGA (The Cancer Genome Atlas, to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  18. Transcriptome Profiling in Human Diseases: New Advances and Perspectives.

    Science.gov (United States)

    Casamassimi, Amelia; Federico, Antonio; Rienzo, Monica; Esposito, Sabrina; Ciccodicola, Alfredo

    2017-07-29

    In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements) and TCGA (The Cancer Genome Atlas), to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  19. Serological prevalence of human parvovirus B19 in diseases or disordersrelated to different human body systems.

    Science.gov (United States)

    Aktaş, Osman; Aydin, Hakan; Uslu, Hakan

    2016-02-17

    Human parvovirus B19 is a pathogen that affects different parts of the body. We planned this study because of the lack of data on B19 seroprevalence based on different body-system diseases. The prevalence of parvovirus B19 antibodies was investigated retrospectively in 1239 patients by review of medical records from 2009-2012, according to their diseases classified under general titles in compliance with the International Classification of Diseases (ICD-10). Parvovirus B19-specific antibodies were detected by quantitative enzyme immunoassays. The positivity rate was 27.8% for only IgG, 8.5% for only IgM, and 2.6% for both IgG and IgM. The highest positivity for IgG alone was found in musculoskeletal system and connective tissue diseases (55.9%), while the highest positivity for IgM was found in neoplasms (16.4%). The highest positivity for IgG was seen in rheumatoid arthritis (72.2%) and pregnancy (52.6%), and the highest positivity for total IgM was found in upper respiratory tract disease (21.0%) and hepatic failure (17.1%). Parvovirus B19 seroprevalence was relatively low in northeastern Anatolia compared to most serological studies conducted in other regions. We think that this study has provided the first wide-ranging information on the seroprevalence of B19 in diseases and disorders of the major human body systems.

  20. Exploring the potential relevance of human-specific genes to complex disease

    Directory of Open Access Journals (Sweden)

    Cooper David N

    2011-01-01

    Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

  1. Mutations that Cause Human Disease: A Computational/Experimental Approach

    Energy Technology Data Exchange (ETDEWEB)

    Beernink, P; Barsky, D; Pesavento, B

    2006-01-11

    International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximately half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which

  2. Mitochondrial regulation of epigenetics and its role in human diseases

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Tollefsbol, Trygve O; Singh, Keshav K

    2012-01-01

    as the sole pathogenic factor suggesting that additional mechanisms contribute to lack of genotype and clinical phenotype correlationship. An increasing number of studies have identified a possible effect on the epigenetic landscape of the nuclear genome as a consequence of mitochondrial dysfunction....... In particular, these studies demonstrate reversible or irreversible changes in genomic DNA methylation profiles of the nuclear genome. Here we review how mitochondria damage checkpoint (mitocheckpoint) induces epigenetic changes in the nucleus. Persistent pathogenic mutations in mtDNA may also lead...... to epigenetic changes causing genomic instability in the nuclear genome. We propose that "mitocheckpoint" mediated epigenetic and genetic changes may play key roles in phenotypic variation related to mitochondrial diseases or host of human diseases in which mitochondrial defect plays a primary role....

  3. Crossed wires: 3D genome misfolding in human disease.

    Science.gov (United States)

    Norton, Heidi K; Phillips-Cremins, Jennifer E

    2017-11-06

    Mammalian genomes are folded into unique topological structures that undergo precise spatiotemporal restructuring during healthy development. Here, we highlight recent advances in our understanding of how the genome folds inside the 3D nucleus and how these folding patterns are miswired during the onset and progression of mammalian disease states. We discuss potential mechanisms underlying the link among genome misfolding, genome dysregulation, and aberrant cellular phenotypes. We also discuss cases in which the endogenous 3D genome configurations in healthy cells might be particularly susceptible to mutation or translocation. Together, these data support an emerging model in which genome folding and misfolding is critically linked to the onset and progression of a broad range of human diseases. © 2017 Norton and Phillips-Cremins.

  4. Use of rodents as models of human diseases

    Directory of Open Access Journals (Sweden)

    Thierry F Vandamme

    2014-01-01

    Full Text Available Advances in molecular biology have significantly increased the understanding of the biology of different diseases. However, these discoveries have not yet been fully translated into improved treatments for patients with diseases such as cancers. One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. In this brief review, we will discuss the advantages and disadvantages of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM models, we will review some of the current genetic strategies for modeling diseases in the mouse and the preclinical studies that have already been undertaken. We will also discuss how recent improvements in imaging technologies may increase the information derived from using these GEMs during early assessments of potential therapeutic pathways. Furthermore, it is interesting to note that one of the values of using a mouse model is the very rapid turnover rate of the animal, going through the process of birth to death in a very short timeframe relative to that of larger mammalian species.

  5. Molecular mechanisms of acrolein toxicity: relevance to human disease.

    Science.gov (United States)

    Moghe, Akshata; Ghare, Smita; Lamoreau, Bryan; Mohammad, Mohammad; Barve, Shirish; McClain, Craig; Joshi-Barve, Swati

    2015-02-01

    Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. [Unconventional disease agents--a danger for humans and animals?].

    Science.gov (United States)

    Kaaden, O R

    1994-02-01

    The occurrence of bovine spongiform encephalopathy (BSE) in Great Britain in 1985/86, has focused again the public concern as well as scientific interest to the Scrapie disease of sheep and goat known more than 150 years. The agents of scrapie and BSE are characterized by unusual biological and physical-chemical properties, especially their high tenacity. Therefore, they are also designated "unconventional agents of viruses". Different theories have been proposed about their infectious characteristics--especially because of the apparent or real missing of an agent-specific nucleic acid--which are named Virinos, Prions or Nemavirus. The broad host range of Scrapie respective BSE, which includes domestic and wild ruminants, Suidae, Felidae, Mustelidae, small rodents, birds and non-primates, has created some concern since there might be an aetiological correlation between the transmissible spongiform encephalopathies of man (Creutzfeld-Jakob- and Gerstmann-Sträussler-Scheinker-Disease) and that of animals. Although at present neither epidemiological nor molecular biological evidence whatsoever was proved, the hypothesis cannot be completely disproved. The probability of infection through digestive tract seems to be rather unlikely but special precautions should be taken as far as production, investigation and application of human medicine drugs of animal origin. Furthermore, research about the aetiology of "unconventional agents" and pathogenesis of resulting diseases is necessary and should be intensified in Germany. Finally, only an early intra vitam-Diagnose and in vitro detection can avoid an further spread of this new category of diseases.

  7. James Bay Development Corporation annual report, 1986. Societe de Developpement de la Baie James et entites affiliees rapport annuel, 1986

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    The James Bay Development Corporation is a paragovernmental body whose objective is to promote the development and exploitation of those natural resources, other than hydroelectric, which are found in the James Bay region of Quebec. It also oversees the administration and infrastructure management in the territory. This report reviews the year's activities of the Corporation and its affiliates involved in tourism, native development, mining, and municipal affairs. Most of the report consists of financial statements.

  8. Bioprinted three dimensional human tissues for toxicology and disease modeling.

    Science.gov (United States)

    Nguyen, Deborah G; Pentoney, Stephen L

    2017-03-01

    The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Melanopsin-expressing retinal ganglion cells: implications for human diseases

    DEFF Research Database (Denmark)

    La Morgia, Chiara; Ross-Cisneros, Fred N; Hannibal, Jens

    2011-01-01

    In the last decade, there was the seminal discovery of melanopsin-expressing retinal ganglion cells (mRGCs) as a new class of photoreceptors that subserve the photoentrainment of circadian rhythms and other non-image forming functions of the eye. Since then, there has been a growing research...... interest on these cells, mainly focused on animal models. Only recently, a few studies have started to address the relevance of the mRGC system in humans and related diseases. We recently discovered that mRGCs resist neurodegeneration in two inherited mitochondrial disorders that cause blindness, i...

  10. Regulatory Role of Small Nucleolar RNAs in Human Diseases

    Directory of Open Access Journals (Sweden)

    Grigory A. Stepanov

    2015-01-01

    Full Text Available Small nucleolar RNAs (snoRNAs are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs, namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.

  11. Control of human parasitic diseases: Context and overview.

    Science.gov (United States)

    Molyneux, David H

    2006-01-01

    The control of parasitic diseases of humans has been undertaken since the aetiology and natural history of the infections was recognized and the deleterious effects on human health and well-being appreciated by policy makers, medical practitioners and public health specialists. However, while some parasitic infections such as malaria have proved difficult to control, as defined by a sustained reduction in incidence, others, particularly helminth infections can be effectively controlled. The different approaches to control from diagnosis, to treatment and cure of the clinically sick patient, to control the transmission within the community by preventative chemotherapy and vector control are outlined. The concepts of eradication, elimination and control are defined and examples of success summarized. Overviews of the health policy and financing environment in which programmes to control or eliminate parasitic diseases are positioned and the development of public-private partnerships as vehicles for product development or access to drugs for parasite disease control are discussed. Failure to sustain control of parasites may be due to development of drug resistance or the failure to implement proven strategies as a result of decreased resources within the health system, decentralization of health management through health-sector reform and the lack of financial and human resources in settings where per capita government expenditure on health may be less than $US 5 per year. However, success has been achieved in several large-scale programmes through sustained national government investment and/or committed donor support. It is also widely accepted that the level of investment in drug development for the parasitic diseases of poor populations is an unattractive option for pharmaceutical companies. The development of partnerships to specifically address this need provides some hope that the intractable problems of the treatment regimens for the trypanosomiases and

  12. Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

    Science.gov (United States)

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  13. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Directory of Open Access Journals (Sweden)

    Andrew Specht

    2011-01-01

    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  14. RNA FISH for detecting expanded repeats in human diseases.

    Science.gov (United States)

    Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J

    2016-04-01

    RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes. The partial or complete retention of mutant transcripts forming RNA aggregates within the nucleoplasm has been shown in multiple cellular disease models and in the tissues of patients affected with these atypical mutations. Relevant diseases include, among others, myotonic dystrophy type 1 (DM1) with CUG repeats, Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) with CAG repeats, fragile X-associated tremor/ataxia syndrome (FXTAS) with CGG repeats, myotonic dystrophy type 2 (DM2) with CCUG repeats, amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) with GGGGCC repeats and spinocerebellar ataxia type 32 (SCA32) with GGCCUG. In this article, we summarize the results obtained with FISH to examine RNA nuclear inclusions. We provide a detailed protocol for detecting RNAs containing expanded CAG and CUG repeats in different cellular models, including fibroblasts, lymphoblasts, induced pluripotent stem cells and murine and human neuronal progenitors. We also present the results of the first single-molecule FISH application in a cellular model of polyglutamine disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Economic Burden of Human Papillomavirus-Related Diseases in Italy

    Science.gov (United States)

    Baio, Gianluca; Capone, Alessandro; Marcellusi, Andrea; Mennini, Francesco Saverio; Favato, Giampiero

    2012-01-01

    Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention. PMID:23185412

  16. Obituary: Michael James Ledlow, 1964-2004

    Science.gov (United States)

    Puxley, Philip John; Grashuis, Randon M.

    2004-12-01

    Michael James Ledlow died on 5 June 2004 from a large, unsuspected brain tumor. Since 2000 he had been on the scientific staff of the Gemini Observatory in La Serena, Chile, initially as a Science Fellow and then as a tenure-track astronomer. Michael was born in Bartlesville, Oklahoma on 1 October 1964 to Jerry and Sharon Ledlow. He obtained his Bachelor Degree in astrophysics at the University of Oklahoma in 1987 and attended the University of New Mexico for his graduate work, obtaining his PhD while studying Galaxy Clusters under Frazer Owen in 1994. From 1995-1997 Michael held a postdoctoral position with Jack Burns at New Mexico State University where he used various astronomical facilities including the VLA and Apache Point Observatory to study distant galaxies. From 1998-2000 Michael rejoined the Physics and Astronomy Department at the University of New Mexico where he was a visiting professor until he moved on to Gemini. At the Gemini Observatory, Mike shared in the excitement, hard work and many long days and nights associated with bringing on-line a major new astronomical facility and its instrumentation. Following its commissioning he assisted visiting observers, supported and took data for many more remote users via the queue system, and for each he showed the same care and attention to detail evident in his own research to ensure that all got the best possible data. His research concentrated on the radio and optical properties of galaxy clusters, especially rich Abell clusters such as A2125, on luminous radio galaxies, including the detection of a powerful double radio source in the "wrong sort of galaxy," the spiral system 0313-192, and on EROs (extremely red objects), dusty galaxies barely detectable at optical wavelengths. Michael thoroughly enjoyed living in Chile and enthusiastically immersed himself in the culture of his surroundings. He and his family were actively involved with the International English Spanish Association in La Serena. He had a

  17. Modeling human diseases: an education in interactions and interdisciplinary approaches

    Directory of Open Access Journals (Sweden)

    Leonard Zon

    2016-06-01

    Full Text Available Traditionally, most investigators in the biomedical arena exploit one model system in the course of their careers. Occasionally, an investigator will switch models. The selection of a suitable model system is a crucial step in research design. Factors to consider include the accuracy of the model as a reflection of the human disease under investigation, the numbers of animals needed and ease of husbandry, its physiology and developmental biology, and the ability to apply genetics and harness the model for drug discovery. In my lab, we have primarily used the zebrafish but combined it with other animal models and provided a framework for others to consider the application of developmental biology for therapeutic discovery. Our interdisciplinary approach has led to many insights into human diseases and to the advancement of candidate drugs to clinical trials. Here, I draw on my experiences to highlight the importance of combining multiple models, establishing infrastructure and genetic tools, forming collaborations, and interfacing with the medical community for successful translation of basic findings to the clinic.

  18. Hepatic cholesterol ester hydrolase in human liver disease.

    Science.gov (United States)

    Simon, J B; Poon, R W

    1978-09-01

    Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

  19. The Spanish biology/disease initiative within the human proteome project: Application to rheumatic diseases.

    Science.gov (United States)

    Ruiz-Romero, Cristina; Calamia, Valentina; Albar, Juan Pablo; Casal, José Ignacio; Corrales, Fernando J; Fernández-Puente, Patricia; Gil, Concha; Mateos, Jesús; Vivanco, Fernando; Blanco, Francisco J

    2015-09-08

    The Spanish Chromosome 16 consortium is integrated in the global initiative Human Proteome Project, which aims to develop an entire map of the proteins encoded following a gene-centric strategy (C-HPP) in order to make progress in the understanding of human biology in health and disease (B/D-HPP). Chromosome 16 contains many genes encoding proteins involved in the development of a broad range of diseases, which have a significant impact on the health care system. The Spanish HPP consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. Proteomics strategies have enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. In this manuscript we describe how the Spanish HPP-16 consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. We show how the Proteomic strategy has enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models.

    Science.gov (United States)

    Sproul, Andrew A

    2015-01-01

    Human pluripotent stem cells (PSCs) have the capacity to revolutionize medicine by allowing the generation of functional cell types such as neurons for cell replacement therapy. However, the more immediate impact of PSCs on treatment of Alzheimer's disease (AD) will be through improved human AD model systems for mechanistic studies and therapeutic screening. This review will first briefly discuss different types of PSCs and genome-editing techniques that can be used to modify PSCs for disease modeling or for personalized medicine. This will be followed by a more in depth analysis of current AD iPSC models and a discussion of the need for more complex multicellular models, including cell types such as microglia. It will finish with a discussion on current clinical trials using PSC-derived cells and the long-term potential of such strategies for treating AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Petroleum possibilities of the James Bay Lowland area: Drilling in the James Bay Lowland

    Energy Technology Data Exchange (ETDEWEB)

    Martison, N W

    1954-12-31

    Interest in the possible occurrence of petroleum and natural gas in the James Bay lowland arises from the presence there of Palaeozoic sedimentary formations resembling those in south-western Ontario. The first part of this report reviews earlier geologic surveys conducted in the lowland and reports results of field work and drill core studies 1946-51. It describes the area`s topography, climate, stratigraphy and palaeontology (Ordovician to Lower Cretaceous, plus Pleistocene and recent glacial deposits), structural geology, and evidence of petroleum. Lists of fossils and correlations are included. The appendices include a list of fossil locations and drill logs. The second part details the drilling programs carried out in the lowland by the Ontario Dept. of Mines, including detailed logs, as well as drilling carried out by some other organisations.

  2. Obituary: James C. Kemp, 1927-1988

    Science.gov (United States)

    Milone, E. F.

    2009-01-01

    James C. Kemp was born in Detroit, Michigan on 9 February 1927, and died in Eugene, Oregon, on 29 March 1988. He went to high school in Mexico City and did undergraduate studies at the University of Michigan and University of California at Berkeley. Kemp was an active observational astronomer, having migrated from earlier interests in Slavic languages, in which he majored, electrical engineering, and physics. He obtained a PhD in electrical engineering at Berkeley in 1960 and did post-doctoral work there with Erwin Hahn on spin resonance. He went to the University of Oregon in 1961 and conducted research in magneto-optics, developing, in the process, a piezo-optical birefringence modulator to measure circular polarization. The modulator is described by Tinbergen (1996). Kemp explored new areas as he measured magnetic fields in the sunspots with polarized infrared light, and developed polarimeters and photometers to study the behavior of such astronomical sources as white dwarfs, the relativistic jets of binary SS 433, the x-ray binary Cyg X-1, and the bright eclipsing binaries Algol and e Aurigae on the 61- and, later, 81-cm telescope at the Pine Mountain Observatory, of which Kemp was director until his death from cancer. His measurement of circularly polarization in the continuum light of the white dwarf GJ 742 (Grw +70∘ 8247, Kemp et al. 1970b) was an important discovery, and through his study of Algol (Kemp et al. 1983; Wilson & Liou 1993), he appears to have been the first to discover the limb polarization in eclipsing binaries predicted by Chandrasekhar (1946ab). Although it has taken twenty years for the BAAS to publish his obituary notice, it is somewhat appropriate that his former student, Gary Henson, who provided much of the background for this article, is involved with a polarimetry team to observe and analyze data from e Aurigae, as it approaches ingress of the next primary minimum beginning summer, 2009. The author acknowledges with gratitude the

  3. RAS signalling in energy metabolism and rare human diseases.

    Science.gov (United States)

    Dard, L; Bellance, N; Lacombe, D; Rossignol, R

    2018-05-08

    The RAS pathway is a highly conserved cascade of protein-protein interactions and phosphorylation that is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Recent findings indicate that the RAS pathway plays a role in the regulation of energy metabolism via the control of mitochondrial form and function but little is known on the participation of this effect in RAS-related rare human genetic diseases. Germline mutations that hyperactivate the RAS pathway have been discovered and linked to human developmental disorders that are known as RASopathies. Individuals with RASopathies, which are estimated to affect approximately 1/1000 human birth, share many overlapping characteristics, including cardiac malformations, short stature, neurocognitive impairment, craniofacial dysmorphy, cutaneous, musculoskeletal, and ocular abnormalities, hypotonia and a predisposition to developing cancer. Since the identification of the first RASopathy, type 1 neurofibromatosis (NF1), which is caused by the inactivation of neurofibromin 1, several other syndromes have been associated with mutations in the core components of the RAS-MAPK pathway. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), which was formerly called LEOPARD syndrome, Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). Here, we review current knowledge about the bioenergetics of the RASopathies and discuss the molecular control of energy homeostasis and mitochondrial physiology by the RAS pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Simian virus 40 infection in humans and association with human diseases: results and hypotheses

    International Nuclear Information System (INIS)

    Barbanti-Brodano, Giuseppe; Sabbioni, Silvia; Martini, Fernanda; Negrini, Massimo; Corallini, Alfredo; Tognon, Mauro

    2004-01-01

    Simian virus 40 (SV40) is a monkey virus that was introduced in the human population by contaminated poliovaccines, produced in SV40-infected monkey cells, between 1955 and 1963. Epidemiological evidence now suggests that SV40 may be contagiously transmitted in humans by horizontal infection, independent of the earlier administration of SV40-contaminated poliovaccines. This evidence includes detection of SV40 DNA sequences in human tissues and of SV40 antibodies in human sera, as well as rescue of infectious SV40 from a human tumor. Detection of SV40 DNA sequences in blood and sperm and of SV40 virions in sewage points to the hematic, sexual, and orofecal routes as means of virus transmission in humans. The site of latent infection in humans is not known, but the presence of SV40 in urine suggests the kidney as a possible site of latency, as it occurs in the natural monkey host. SV40 in humans is associated with inflammatory kidney diseases and with specific tumor types: mesothelioma, lymphoma, brain, and bone. These human tumors correspond to the neoplasms that are induced by SV40 experimental inoculation in rodents and by generation of transgenic mice with the SV40 early region gene directed by its own early promoter-enhancer. The mechanisms of SV40 tumorigenesis in humans are related to the properties of the two viral oncoproteins, the large T antigen (Tag) and the small t antigen (tag). Tag acts mainly by blocking the functions of p53 and RB tumor suppressor proteins, as well as by inducing chromosomal aberrations in the host cell. These chromosome alterations may hit genes important in oncogenesis and generate genetic instability in tumor cells. The clastogenic activity of Tag, which fixes the chromosome damage in the infected cells, may explain the low viral load in SV40-positive human tumors and the observation that Tag is expressed only in a fraction of tumor cells. 'Hit and run' seems the most plausible mechanism to support this situation. The small tag

  5. G protein-coupled receptor mutations and human genetic disease.

    Science.gov (United States)

    Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

    2014-01-01

    Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

  6. Proteome analysis of human substantia nigra in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Werner Cornelius J

    2008-02-01

    Full Text Available Abstract Background Parkinson's disease (PD is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra. Results The gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin and glutathione-related redox metabolism (GST M3, GST P1, GST O1, including novel redox proteins (SH3BGRL. Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin, as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation, aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism. Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results. Conclusion Using an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many

  7. Obituary: James N. Kile, 1958-2007

    Science.gov (United States)

    Cliver, Edward W.; Lang, Kenneth R.; Willson, Robert F.

    2009-01-01

    James N. Kile, of Needham Heights, Massachusetts, died on 17 August 2007, following a brave two-year battle with cancer. One of three children of David R. Kile and Betty Jane Kile, Jim was born in Niagara Falls, New York, on 20 April 1958 and lived in the nearby village of Lewiston before his family settled in Alden, an hour east of Niagara Falls, when Jim was nine. Jim's father worked for American Telephone and Telegraph for 37 years, and his mother was a homemaker. Jim earned his Bachelor's degree in Physics from Rensselaer Polytechnic Institute in 1980, a Master's degree from Northwestern University in 1982, and a Doctorate from Tufts University in 1996 under the direction of Robert Willson. His thesis involved comparison of radio data from the Very Large Array and the Russian RATAN 600 telescope with Yohkoh soft X-ray data, with an emphasis on understanding the relationship between solar noise storms and coronal magnetic fields. While working on his thesis, Jim collaborated with one of us (EWC) at the Air Force Research Laboratory on an investigation of the 154-day periodicity in solar flares. The resulting publication (ApJ 370, 442, 1991) is his most cited work. Jim co-authored four other papers in refereed journals. Jim's professional affiliations included the American Astronomical Society, the American Institute of Aeronautics and Astronautics, the American Geophysical Union, and the Astronomical Society of the Pacific. Jim worked as a contractor in the defense industry from 1982 until the time of his death, settling in the Boston area in the early 1980s. He worked for Calspan Corporation from 1982-1989, the Ultra Corporation from 1989-1994, and the Riverside Research Institute from 1994-2007. He was a highly-respected expert in radar systems, including radar data and systems analysis, systems engineering, and planning support for radar acquisition programs and technology development. The work entailed frequent extended travel to Norway for system testing

  8. The Scientific Papers of James Clerk Maxwell

    Science.gov (United States)

    Clerk Maxwell, James; Niven, W. D.

    2011-01-01

    homogeneous quadratic functions; 57. On the focal lines of a refracted pencil; 58. An Essay on the mathematical principles of physics. By Rev. James Challis. (Review); 59. On Loschmidt's experiments on diffusion in relation to the kinetic theory of gases; 60. On the final state of a system of molecules in motion subject to forces of any kind; 61. Faraday; 62. Molecules (a lecture); 63. On double refraction in a viscous fluid in motion; 64. On Hamilton's characteristic function for a narrow beam of light; 65. On the relation of geometrical optics to other parts of mathematics and physics; 66. Plateau on soap-bubbles (Review); 67. Grove's Correlation of physical forces (Review); 68. On the application of Kirchhoff's rules for electric circuits to the solution of a geometric problem; 69. Van der Waals on the continuity of the gaseous and liquid states; 70. On the centre of motion of the eye; 71. On the dynamical evidence of the molecular constitution of bodies (a lecture); 72. On the application of Hamilton's characteristic function to the theory of an optical instrument symmetrical about its axis; 73. Atom; 74. Attraction; 75. On Bow's method of drawing diagrams in graphical statics with illustrations from Peaucellier's Linkage; 76. On the equilibrium of heterogeneous substances; 77. Diffusion of gases through absorbing substances; 78. General considerations concerning scientific apparatus; 79. Instruments connected with fluids; 80. Whewell's Writing and correspondence (Review); 81. On Ohm's Law; 82. On the protection of buildings from lightning; 83. Capillary action; 84. Hermann Ludwig Ferdinand Helmholtz; 85. On a paradox in the theory of attraction; 86. On approximate multiple integration between limits by summation; 87. On the unpublished electrical papers of the Hon. Henry Cavendish; 88. Constitution of bodies; 89. Diffusion; 90. Diagrams; 91. Tait's Thermo

  9. Impacts of environment on human diseases: a web service for the human exposome

    Science.gov (United States)

    Karssenberg, Derek; Vaartjes, Ilonca; Kamphuis, Carlijn; Strak, Maciek; Schmitz, Oliver; Soenario, Ivan; de Jong, Kor

    2017-04-01

    The exposome is the totality of human environmental exposures from conception onwards. Identifying the contribution of the exposome to human diseases and health is a key issue in health research. Examples include the effect of air pollution exposure on cardiovascular diseases, the impact of disease vectors (mosquitos) and surface hydrology exposure on malaria, and the effect of fast food restaurant exposure on obesity. Essential to health research is to disentangle the effects of the exposome and genome on health. Ultimately this requires quantifying the totality of all human exposures, for each individual in the studied human population. This poses a massive challenge to geoscientists, as environmental data are required at a high spatial and temporal resolution, with a large spatial and temporal coverage representing the area inhabited by the population studied and the time span representing several decades. Then, these data need to be combined with space-time paths of individuals to calculate personal exposures for each individual in the population. The Global and Geo Health Data Centre is taking this challenge by providing a web service capable of enriching population data with exposome information. Our web service can generate environmental information either from archived national (up to 5 m spatial and 1 h temporal resolution) and global environmental information or generated on the fly using environmental models running as microservices. On top of these environmental data services runs an individual exposure service enabling health researchers to select different spatial and temporal aggregation methods and to upload space-time paths of individuals. These are then enriched with personal exposures and eventually returned to the user. We illustrate the service in an example of individual exposures to air pollutants calculated from hyper resolution air pollution data and various approaches to estimate space-time paths of individuals.

  10. The inauguration of Robert-Bourassa Park at James Bay

    International Nuclear Information System (INIS)

    Valiquette, M.

    1997-01-01

    Robert Bourassa's contributions to the hydroelectric development at James Bay were acknowledged with the inauguration of a park in the ex-prime minister's name. Phase 1 of the James Bay hydroelectric project constituted the world's biggest construction site, employing more than 180,000 people from beginning to project completion. The James Bay project allowed Hydro-Quebec to gain one of the world's largest electric power utilities and to gain significant competitive edge over its competitors. The Robert Bourassa Park contains a picnic area and a visitor interpretation centre which describes the history of the project. A sequence of 5 signposts summarize the contributions that Robert Bourassa made to the megaproject which cost over $20.6 billion. The complex consists of 65 turbines which produce 15,235 megawatts of electricity. 1 fig

  11. Host control of human papillomavirus infection and disease.

    Science.gov (United States)

    Doorbar, John

    2018-02-01

    Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

  12. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Fifth People' s Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, 200240 (China); Zhao, Libo [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Third People' s Hospital of Chongqing, 400014 (China); Yang, Yongtao [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Bode, Liv [Bornavirus Research Group affiliated to the Free University of Berlin, Berlin (Germany); Huang, Hua [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Liu, Chengyu [Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Huang, Rongzhong [Department of Rehabilitative Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 (China); Zhang, Liang [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  13. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    International Nuclear Information System (INIS)

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang

    2014-01-01

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs

  14. James Webb Telescope's Near Infrared Camera: Making Models, Building Understanding

    Science.gov (United States)

    Lebofsky, Larry A.; McCarthy, D. W.; Higgins, M. L.; Lebofsky, N. R.

    2010-10-01

    The Astronomy Camp for Girl Scout Leaders is a science education program sponsored by NASA's next large space telescope: The James Webb Space Telescope (JWST). The E/PO team for JWST's Near Infrared Camera (NIRCam), in collaboration with the Sahuaro Girl Scout Council, has developed a long-term relationship with adult leaders from all GSUSA Councils that directly benefits troops of all ages, not only in general science education but also specifically in the astronomical and technology concepts relating to JWST. We have been training and equipping these leaders so they can in turn teach young women essential concepts in astronomy, i.e., the night sky environment. We model what astronomers do by engaging trainers in the process of scientific inquiry, and we equip them to host troop-level astronomy-related activities. It is GSUSA's goal to foster girls’ interest and creativity in Science, Technology, Engineering, and Math, creating an environment that encourages their interests early in their lives while creating a safe place for girls to try and fail, and then try again and succeed. To date, we have trained over 158 leaders in 13 camps. These leaders have come from 24 states, DC, Guam, and Japan. While many of the camp activities are related to the "First Light” theme, many of the background activities relate to two of the other JWST and NIRCam themes: "Birth of Stars and Protoplanetary Systems” and "Planetary Systems and the Origin of Life.” The latter includes our own Solar System. Our poster will highlight the Planetary Systems theme: 1. Earth and Moon: Day and Night; Rotation and Revolution. 2. Earth/Moon Comparisons. 3. Size Model: The Diameters of the Planets. 4. Macramé Planetary (Solar) Distance Model. 5.What is a Planet? 6. Planet Sorting Cards. 7. Human Orrery 8. Lookback Time in Our Daily Lives NIRCam E/PO website: http://zeus.as.arizona.edu/ dmccarthy/GSUSA

  15. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    Science.gov (United States)

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  16. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)

  17. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed

  18. [Demyelinating disease and vaccination of the human papillomavirus].

    Science.gov (United States)

    Álvarez-Soria, M Josefa; Hernández-González, Amalia; Carrasco-García de León, Sira; del Real-Francia, M Ángeles; Gallardo-Alcañiz, M José; López-Gómez, José L

    2011-04-16

    Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered. We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.

  19. Alkaptonuria is a novel human secondary amyloidogenic disease.

    Science.gov (United States)

    Millucci, Lia; Spreafico, Adriano; Tinti, Laura; Braconi, Daniela; Ghezzi, Lorenzo; Paccagnini, Eugenio; Bernardini, Giulia; Amato, Loredana; Laschi, Marcella; Selvi, Enrico; Galeazzi, Mauro; Mannoni, Alessandro; Benucci, Maurizio; Lupetti, Pietro; Chellini, Federico; Orlandini, Maurizio; Santucci, Annalisa

    2012-11-01

    Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was examined using immunofluorescence and their levels were evaluated in the patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co-localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits assessed secondary type of amyloidosis. High levels of SAA and SAP were found in AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of patients' abdominal fat and salivary gland. AKU is the second pathology after Parkinson's disease where amyloid is associated with a form of melanin. Aberrant expression of proteins involved in amyloidogenesis has been found in AKU cells. Our findings on alkaptonuria as a novel type II AA amyloidosis open new important perspectives for its therapy, since methotrexate treatment proved to significantly reduce in vitro HGA-induced A-amyloid aggregates. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Human lipodystrophies: genetic and acquired diseases of adipose tissue

    Science.gov (United States)

    Capeau, Jacqueline; Magré, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bénédicte; Béréziat, Véronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

    2010-01-01

    Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARγ. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664

  1. James Parkinson and his essay on "shaking palsy", two hundred years later.

    Science.gov (United States)

    Palacios-Sánchez, Leonardo; Torres Nupan, Martha; Botero-Meneses, Juan Sebastián

    2017-09-01

    In 1817, British physician James Parkinson published a 66-page document entitled "Essay on the Shaking Palsy". This brief text became a classical and fundamental piece in the history of medicine and, in particular, of neurology. The authors of this article wish to pay tribute to this great pioneer of neurology, 200 years after the publication of his findings, which would, in turn, immortalize his name and give rise to the renaming on the entity in 1860 by Professor Jean Martin Charcot, father of neurology. It would be known, henceforth as Parkinson's disease.

  2. Regional ventilation/perfusion mismatch pattern in patient with Swyer James (MacLeod′s syndrome

    Directory of Open Access Journals (Sweden)

    Sait Sager

    2014-01-01

    Full Text Available Swyer James (McLeod′s syndrome (SJMS is an uncommon disease, which occurs as a result of childhood bronchiolitis obliterans. Patients may not be diagnosed until later in their life. A 46-year-old man underwent ventilation/perfusion scintigraphy for acute onset of dyspnea. The scan showed markedly diminished ventilation and perfusion unilaterally on the right middle and inferior lobes. However, mismatched ventilation-perfusion pattern was shown on the upper right lobe, which was consistent with pulmonary embolism. Unilaterally matched ventilation/perfusion defect can see in SJMS in lung scintigraphy; however, when pulmoner embolism may accompany, scintigraphy should be carefully examined.

  3. James Parkinson and his essay on “shaking palsy”, two hundred years later

    Directory of Open Access Journals (Sweden)

    Leonardo Palacios-Sánchez

    Full Text Available ABSTRACT In 1817, British physician James Parkinson published a 66-page document entitled “Essay on the Shaking Palsy”. This brief text became a classical and fundamental piece in the history of medicine and, in particular, of neurology. The authors of this article wish to pay tribute to this great pioneer of neurology, 200 years after the publication of his findings, which would, in turn, immortalize his name and give rise to the renaming on the entity in 1860 by Professor Jean Martin Charcot, father of neurology. It would be known, henceforth as Parkinson’s disease.

  4. Swyer- James -MacLeod syndrome presenting as hemoptysis in an adult

    Directory of Open Access Journals (Sweden)

    Santosh Kumar

    2012-01-01

    Full Text Available Swyer-James/MacLeod syndrome is an uncommon disease with characteristic radiological feature of unilateral hyperlucency due to loss of pulmonary vasculature and air trapping. Typically, this disorder is diagnosed in childhood during evaluations for recurrent respiratory infections. Here, we report a case in a 30-year-old adult female who presented with dyspnoea, cough with expectoration and recurrent hemoptysis due to associated bronchiectasis. This case highlights the importance of computed tomography in the diagnostic workup of recurrent hemoptysis in pulmonary tuberculosis epidemic countries like India

  5. Unheard voices: James Bay II and the women of Kuujjuarapik

    International Nuclear Information System (INIS)

    Hawkes, S.

    1991-01-01

    The attitudes held by the aboriginal peoples of the James Bay region toward the James Bay II hydroelectric power development are described. These attitudes are communicated primarily through the comments of Innu women. Major concerns with the Great Whale project relate to its impact on country food, mercury contamination, and camps. The entire community of Kuujjuarapik was totally opposed to the Great Whale project. While direct impacts such as mercury contamination or reduced wildlife harvest are the most obvious impacts, indirect impacts relating to cultural damage, increased abuse and alcoholism, and influx of non-native construction workers will also have significant effects, and warrant further study

  6. Unheard voices: James Bay II and the women of Kuujjuarapik

    Energy Technology Data Exchange (ETDEWEB)

    Hawkes, S. (Waterloo Univ., ON (Canada))

    The attitudes held by the aboriginal peoples of the James Bay region toward the James Bay II hydroelectric power development are described. These attitudes are communicated primarily through the comments of Innu women. Major concerns with the Great Whale project relate to its impact on country food, mercury contamination, and camps. The entire community of Kuujjuarapik was totally opposed to the Great Whale project. While direct impacts such as mercury contamination or reduced wildlife harvest are the most obvious impacts, indirect impacts relating to cultural damage, increased abuse and alcoholism, and influx of non-native construction workers will also have significant effects, and warrant further study.

  7. Consent: a Cartesian ideal? Human neural transplantation in Parkinson's disease.

    Science.gov (United States)

    Lopes, Manuel; Meningaud, Jean-Paul; Behin, Anthony; Hervé, Christian

    2003-01-01

    The grafting of human embryonic cells in Parkinson's disease is an innovative and hopefully useful therapeutic approach. However, it still concerns a very small number of patients and is only suggested as a research protocol. We present here a study of the problems of information and consent to research within the framework of this disease in which the efficacy of medical treatment is shortlived. The only French center to use this treatment (Hôpital H. Mondor in Créteil) has received authorization from the Comité Consultatif National d'Ethique (Consultative National Committee on Ethics). Eleven patients were treated between 1991 and 1998. The study of the results of a questionnaire sent to those patients showed the difficulties met in evaluating the perception of information despite intact intellectual capacities in people "prepared to risk everything." In France, the duty to inform patients during research procedures is regulated by the Huriet Act. However, it is not easy to guarantee genuine consent when preliminary information is given to patients psychologically impaired by the slow and ineluctable course of their disease. In these borderline cases, a valid consent seems to be a myth in terms of pure autonomy when considered with the Cartesian aim of elimination of uncertainty. The relevance of this concept of genuine consent probably makes more sense as aiming at a Cartesian ideal which is perhaps more in the spirit rather than in the letter. It is in that same spirit that, from the outset, we propose to define t he practical ways of answering the patients' request for information, even sometimes after consent has been given.

  8. The medical science fiction of James White: Inside and Outside Sector General.

    Science.gov (United States)

    Howard, Richard

    2016-12-01

    James White was a Northern Irish science fiction author working in the subgenre of medical science fiction from the mid-1950s to the end of the twentieth century. The aim of this article is to introduce White to scholars working in the medical humanities, pointing to features of interest and critiquing the more excessive utopian impulses of the author. The article covers White's Sector General series, set on a vast intergalactic hospital, as well as the author's standalone fictions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  10. Effects of environmental pollutants on cellular iron homeostasis and ultimate links to human disease

    Science.gov (United States)

    Chronic disease has increased in the last several decades, and environmental pollutants have been implicated. The magnitude and variety of diseases indicate the malfunctioning of some basic mechanism underlying human health. Environmental pollutants demonstrate a capability to co...

  11. Human prion diseases in The Netherlands : clinico-pathological, genetic and molecular aspects

    NARCIS (Netherlands)

    Jansen, C.

    2011-01-01

    Prion diseases, or transmissible spongiform encephalopathies (TSEs), are invariably fatal neurodegenerative disorders that can be sporadic, inherited or acquired by infection. In humans, TSEs comprise three major groups showing a wide phenotypic heterogeneity: Creutzfeldt-Jakob disease (CJD),

  12. James Van Allen and His Namesake NASA Mission

    Science.gov (United States)

    Baker, D. N.; Hoxie, V. C.; Jaynes, A.; Kale, A.; Kanekal, S. G.; Li, X.; Reeves, G. D.; Spence, H. E.

    2013-12-01

    In many ways, James A. Van Allen defined and "invented" modern space research. His example showed the way for government-university partners to pursue basic research that also served important national and international goals. He was a tireless advocate for space exploration and for the role of space science in the spectrum of national priorities.

  13. Keening Woman and Today: James Welch's Early Unpublished Novel

    Science.gov (United States)

    Orton, Thomas

    2006-01-01

    It was most likely in the spring of 1966 that the late American Indian novelist James Welch wrote his first novel, predating his first published fiction by eight years. The titleless, hand-corrected typescript, stored in his Missoula home for many years, is 114 pages long and unfinished. The book is playful and experimental the way warm-ups…

  14. James J. Gallagher: Man in the White Hat

    Science.gov (United States)

    Jolly, Jennifer L.; Robinson, Ann

    2014-01-01

    In classic Western movies, the good guy could be frequently identified by his trademark white Stetson hat, whereas the bad guy always wore black. James J. Gallagher wore many hats during his career that spanned over six decades; he too would be known as the "man in the white hat,"--trusted to do the right thing. From 1967 to 1970,…

  15. Engineering new medicine: an interview with James Collins.

    Science.gov (United States)

    Collins, James

    2010-01-01

    At first glance, the commonality among synthetic gene networks, nerve cell response times and the emergence of antibiotic resistance is obscure. Yet, when speaking with James (Jim) Collins, the relationship becomes clear: all are applications-oriented problems, and all inspire unique approaches from this unusual engineer who is empowered by his freedom to fail.

  16. Groundbreaking Investigator of Creativity: An Interview with James C. Kaufman

    Science.gov (United States)

    Henshon, Suzanna E.

    2010-01-01

    This article presents an interview with James C. Kaufman, an associate professor of psychology at the California State University at San Bernardino, where he directs the Learning Research Institute. Kaufman received his PhD in cognitive psychology from Yale University in 2001. Dr. Kaufman's research broadly focuses on nurturing and encouraging…

  17. 75 FR 13323 - James A. Fitzpatrick Nuclear Power Plant; Exemption

    Science.gov (United States)

    2010-03-19

    ... Power Plant; Exemption 1.0 Background Entergy Nuclear Operations, Inc. (the licensee) is the holder of... nuclear power plants that were licensed before January 1, 1979, satisfy the requirements of 10 CFR Part 50...), as supplemented by letter dated March 30, 2009, ``James A. FitzPatrick Nuclear Power Plant-Response...

  18. 75 FR 16520 - James A. Fitzpatrick Nuclear Power Plant; Exemption

    Science.gov (United States)

    2010-04-01

    ... Power Plant; Exemption 1.0 Background Entergy Nuclear Operations, Inc. (the licensee) is the holder of Facility Operating License No. DPR-59, which authorizes operation of the James A. FitzPatrick Nuclear Power... date for all operating nuclear power plants, but noted that the Commission's regulations provide...

  19. James Madison High: A School at the Crossroads

    Science.gov (United States)

    Stroup, John T.; Salmonowicz, Michael J.; Broom, Christopher C.

    2007-01-01

    This case tells the story of James Madison High School, which became the epicenter of a debate over the future reorganization and control of large secondary schools in the Los Angeles Unified School District (LAUSD). The LAUSD, recently taken over by the newly elected mayor, was fighting for control of this 3,000-student high school with a charter…

  20. James Madison's "Public" As Interpreter of the Constitution.

    Science.gov (United States)

    Dewey, Donald O.

    James Madison's thoughts on various interpretations of the Constitution maintain that public opinion is the ultimate method of legitimizing the document. The Constitution must prevail against mere public opinion, but public opinion may be used to establish the meaning of the Constitution when conflicting interpretations exist. The public good and…

  1. THE JAMES MADISON WOOD QUADRANGLE, STEPHENS COLLEGE, COLUMBIA, MISSOURI.

    Science.gov (United States)

    MCBRIDE, WILMA

    THE JAMES MADISON WOOD QUADRANGLE AT STEPHENS COLLEGE IS A COMPLEX OF BUILDINGS DESIGNED TO MAKE POSSIBLE A FLEXIBLE EDUCATIONAL ENVIRONMENT. A LIBRARY HOUSES A GREAT VARIETY OF AUDIO-VISUAL RESOURCES AND BOOKS. A COMMUNICATION CENTER INCORPORATES TELEVISION AND RADIO FACILITIES, A FILM PRODUCTION STUDIO, AND AUDIO-VISUAL FACILITIES. THE LEARNING…

  2. Looking Backward: James Madison University's General Education Reform.

    Science.gov (United States)

    Reynolds, Charles W.; Allain, Violet Anselmini; Erwin, T. Dary; Halpern, Linda Cabe; McNallie, Robin; Ross, Martha K.

    1998-01-01

    Describes the new general education program at James Madison University (Virginia) and the process by which it was developed. Indicates that the program is organized by five broad areas of knowledge that are defined by interdisciplinary clusters of learning objectives, which in turn were developed using input from every academic department on…

  3. The James Madison College Student Handbook, 1970-71.

    Science.gov (United States)

    Michigan State Univ., East Lansing. James Madison Coll.

    James Madison College of Michigan State University provides a 4-year, residentially-based program devoted to the study of major social, economic, and political policy problems. It offers 5 fields of concentration: (1) Ethnic and Religious Intergroup Relations Policy Problems; (2) International Relations Policy Problems; (3) Justice, Morality and…

  4. "To Mediate Relevantly": A Response to James Simpson

    Science.gov (United States)

    Waters, Alan

    2009-01-01

    In Waters (2009), it was contended that, because of its ideological orientation, a good deal of applied linguistics for language teaching (ALLT) fails to "mediate relevantly" between academic and practitioner perspectives. James Simpson's rejoinder to my article (Simpson 2009) attempts to refute its claims. However, in my view, it fails to do so,…

  5. James Brown, Sample Culture and the Permanent Distance of Glory

    Directory of Open Access Journals (Sweden)

    Steve Jones

    2009-12-01

    Full Text Available The James Brown song ‘I’m Real’ (1988 features lyrics regaled from James Brown’s back catalogue, alongside vocal samples extracted from his earlier hits. As one of the most sampled artists of the hip-hop era, James employed sampling in order to reclaim his position as the “Godfather of Soul” and express his disatisfaction at having his work overtly plundered. The central questions I pose here focus on what the choice to sample himself reveals about Brown’s status as a Soul legend, and whether the contemporaneous James could sincerely live up to the mythic status inherent to the message of ‘I’m Real’ given its self-conscious form. This confusion appears to be an extension of Walter Benjamin’s conception of déjà vu as an acoustic effect - ‘the cool tomb of long ago, from the vault of which the present seems to return only as an echo’ (Benjamin cited in Breyley, 2009: 145 - only here the slippage between past and present is quite literal, involving the discordant imbrication of two divergent temporal states. Via a detailed investigation of the song ‘I’m Real‘, I will probe Brown’s playful employment of his own past. His gambit, I will argue, may be read simultaneously as testament to his own glory, and as a signifier that the excesses of egotistic auto-projection were always more distant than they first appeared to be.

  6. The Contributions of James Moir to Physical Chemistry | Loyson ...

    African Journals Online (AJOL)

    James Moir was a pioneering chemist in the early 1900s who played a leading role in various chemical societies in South Africa. Although he was mainly an organic chemist, he was a very good all-round chemist, whose analytical and organic activities have already been covered in this journal. This article examines his ...

  7. Astronaut James Lovell checks body temperature with oral temperature probe

    Science.gov (United States)

    1965-01-01

    Gemini 7 pilot Astronaut James A. Lovell Jr. has temperature check with oral temperature probe attached to his space suit during final preflight preparations for the Gemini 7 space mission. The temperature probe allows doctors to monitor astronauts body temperature at any time during the mission.

  8. Molecular epidemiology of human oral Chagas disease outbreaks in Colombia.

    Directory of Open Access Journals (Sweden)

    Juan David Ramírez

    Full Text Available BACKGROUND: Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI. In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing and mtMLST (mitochondrial Multilocus Sequence Typing strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. CONCLUSIONS: These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed.

  9. Vibrio cholerae Infection of Drosophilamelanogaster Mimics the Human Disease Cholera.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Cholera, the pandemic diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, continues to be a major public health challenge in the developing world. Cholera toxin, which is responsible for the voluminous stools of cholera, causes constitutive activation of adenylyl cyclase, resulting in the export of ions into the intestinal lumen. Environmental studies have demonstrated a close association between V. cholerae and many species of arthropods including insects. Here we report the susceptibility of the fruit fly, Drosophila melanogaster, to oral V. cholerae infection through a process that exhibits many of the hallmarks of human disease: (i death of the fly is dependent on the presence of cholera toxin and is preceded by rapid weight loss; (ii flies harboring mutant alleles of either adenylyl cyclase, Gsalpha, or the Gardos K channel homolog SK are resistant to V. cholerae infection; and (iii ingestion of a K channel blocker along with V. cholerae protects wild-type flies against death. In mammals, ingestion of as little as 25 mug of cholera toxin results in massive diarrhea. In contrast, we found that ingestion of cholera toxin was not lethal to the fly. However, when cholera toxin was co-administered with a pathogenic strain of V. cholerae carrying a chromosomal deletion of the genes encoding cholera toxin, death of the fly ensued. These findings suggest that additional virulence factors are required for intoxication of the fly that may not be essential for intoxication of mammals. Furthermore, we demonstrate for the first time the mechanism of action of cholera toxin in a whole organism and the utility of D. melanogaster as an accurate, inexpensive model for elucidation of host susceptibility to cholera.

  10. EML proteins in microtubule regulation and human disease.

    Science.gov (United States)

    Fry, Andrew M; O'Regan, Laura; Montgomery, Jessica; Adib, Rozita; Bayliss, Richard

    2016-10-15

    The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8: , 110; Dev. Genes Evol. (2000) 210: , 2-10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  11. Human Environmental Disease Network: A computational model to assess toxicology of contaminants.

    Science.gov (United States)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants associated with diverse human disorders. However, the relationships between diseases based on chemical exposure rarely have been studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration of systems biology and chemical toxicology using information on chemical contaminants and their disease relationships reported in the TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships, allowing inclusion of some degrees of significance in the disease-disease associations. Such a network can be used to identify uncharacterized connections between diseases. Examples are discussed for type 2 diabetes (T2D). Additionally, this computational model allows confirmation of already known links between chemicals and diseases (e.g., between bisphenol A and behavioral disorders) and also reveals unexpected associations between chemicals and diseases (e.g., between chlordane and olfactory alteration), thus predicting which chemicals may be risk factors to human health. The proposed human EDN model allows exploration of common biological mechanisms of diseases associated with chemical exposure, helping us to gain insight into disease etiology and comorbidity. This computational approach is an alternative to animal testing supporting the 3R concept.

  12. Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases.

    Science.gov (United States)

    Gundogdu, Aycan; Nalbantoglu, Ufuk

    2017-04-01

    A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome-human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis.

  13. Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases

    Science.gov (United States)

    Nalbantoglu, Ufuk

    2017-01-01

    A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome–human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis. PMID:28785422

  14. Obituary: James Alfred Van Allen, 1914-2006

    Science.gov (United States)

    Ludwig, George H.; McIlwain, Carl Edwin

    2006-12-01

    James Alfred Van Allen, world-renowned space scientist, died 9 August 2006 at the age of ninety-one. He succumbed to heart failure after a ten-week period of declining health. Van Allen served for his entire sixty-seven-year professional career as an amazingly productive researcher, space science spokesman, inspired teacher, and valued colleague. The realization by him and his associates that charged particles are trapped by the Earth's magnetic field began a whole new field of research, magnetospheric physics. Following that initial discovery, he and his associates quickly extended their observations, first to the inner planets, and then to the rest of the planets and beyond. During his tenure at Iowa, he and his group flew instruments on more than sixty successful Earth satellites and planetary spacecraft, including the first missions to the planets Venus, Mars, Jupiter, Saturn, Uranus, and Neptune. Van Allen's lifetime publication list numbers more than 275, of which many are widely-cited, seminal papers. He was the sole author of more than 125 of those papers. Beyond the research laboratory, Van Allen worked energetically throughout his career in establishing space research as a new branch of human inquiry. He was among the most sought-after as a committee member and adviser, working at the highest levels of government, including the White House and Congress, and at all levels of the national and international research establishments. Many presentations in the non-scientific arena helped to bring the exciting discoveries and challenges of space research to the attention of the general public. James Van Allen (Van to his many friends and colleagues) was born on 7 September 1914 on a small farm near Mount Pleasant, Iowa, the second of four sons of Alfred Morris Van Allen and Alma Olney Van Allen. After high school in Mount Pleasant, he entered Iowa Wesleyan College, majoring in physics and graduating summa cum laude. While there, he was introduced to geophysics

  15. Interstitial lung disease associated with human papillomavirus vaccination

    Directory of Open Access Journals (Sweden)

    Yasushi Yamamoto

    2015-01-01

    Full Text Available Vaccinations against the human papillomavirus (HPV have been recommended for the prevention of cervical cancer. HPV-16/18 AS04-adjuvanted vaccines (Cervarix are said to have favourable safety profiles. Interstitial lung diseases (ILDs can occur following exposure to a drug or a biological agent. We report a case of ILD associated with a Cervarix vaccination. A woman in her 40's, with a history of conisation, received three inoculations of Cervarix. Three months later, she presented with a cough and shortness of breath. Findings from a computed tomography of the chest and a transbronchial lung biopsy were consistent with non-specific interstitial pneumonia. Workup eliminated all other causes of the ILD, except for the vaccination. Over the 11 months of the follow-up period, her symptoms resolved without steroid therapy. The onset and spontaneous resolution of the ILD showed a chronological association with the HPV vaccination. The semi-quantitative algorithm revealed that the likelihood of an adverse drug reaction to Cervarix was “Probable”. The outcome was relatively good, but more attention should be paid to a potential risk for HPV vaccinations to cause ILDs. Wherever possible, chest radiographic examinations should be performed in order not to overlook any ILDs.

  16. Comparative Transcriptomic Profiling and Gene Expression for Myxomatous Mitral Valve Disease in the Dog and Human

    Directory of Open Access Journals (Sweden)

    Greg R. Markby

    2017-07-01

    Full Text Available Myxomatous mitral valve disease is the single most important mitral valve disease in both dogs and humans. In the case of the dog it is ubiquitous, such that all aged dogs will have some evidence of the disease, and for humans it is known as Barlow’s disease and affects up to 3% of the population, with an expected increase in prevalence as the population ages. Disease in the two species show many similarities and while both have the classic myxomatous degeneration only in humans is there extensive fibrosis. This dual pathology of the human disease markedly affects the valve transcriptome and the difference between the dog and human is dominated by changes in genes associated with fibrosis. This review will briefly examine the comparative valve pathology and then, in more detail, the transcriptomic profiling and gene expression reported so far for both species.

  17. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    , oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human...... for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  18. Information to prevent human exposure to disease agents associated with wildlife—U.S. Geological Survey circulars on zoonotic disease

    Science.gov (United States)

    Meteyer, Carol U.; Moede Rogall, Gail

    2018-03-05

    The U.S. Geological Survey in collaboration with the U.S. Fish and Wildlife Service and others have published reports with information about geographic distribution, specific pathogens, disease ecology, and strategies to avoid exposure and infection for a selection of zoonotic diseases. Zoonotic diseases are diseases that can be passed from animals to humans, such as rabies and plague. This summary factsheet highlights the reports on plague, bat rabies, and raccoon roundworm with links to all seven zoonotic diseases covered in this series.

  19. Recombinant Newcastle disease virus-vectored vaccines against human and animal infectious diseases.

    Science.gov (United States)

    Duan, Zhiqiang; Xu, Houqiang; Ji, Xinqin; Zhao, Jiafu

    2015-01-01

    Recent advances in recombinant genetic engineering techniques have brought forward a leap in designing new vaccines in modern medicine. One attractive strategy is the application of reverse genetics technology to make recombinant Newcastle disease virus (rNDV) deliver protective antigens of pathogens. In recent years, numerous studies have demonstrated that rNDV-vectored vaccines can induce quicker and better humoral and mucosal immune responses than conventional vaccines and are protective against pathogen challenges. With deeper understanding of NDV molecular biology, it is feasible to develop gene-modified rNDV vaccines accompanied by good safety, high efficacy, low toxicity and better immunogenicity. This review summarizes the development of reverse genetics technology in using NDV as a promising vaccine vector to design new vaccines for human and animal use.

  20. Attributing the human disease burden of foodborne infections to specific sources.

    NARCIS (Netherlands)

    Pires, S.M.; Evers, E.G.; van Pelt, W.; Ayers, T.; Scallan, E.; Angulo, F.J.; Havelaar, A.H.; Hald, T.

    2009-01-01

    Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However, information

  1. Attributing the Human Disease Burden of Foodborne Infections to Specific Sources

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Evers, Eric E.; Van Pely, Wilfrid

    2009-01-01

    Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However...

  2. Global burden of human papillomavirus and related diseases.

    Science.gov (United States)

    Forman, David; de Martel, Catherine; Lacey, Charles J; Soerjomataram, Isabelle; Lortet-Tieulent, Joannie; Bruni, Laia; Vignat, Jerome; Ferlay, Jacques; Bray, Freddie; Plummer, Martyn; Franceschi, Silvia

    2012-11-20

    The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival-less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be

  3. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

    Directory of Open Access Journals (Sweden)

    Amr T. M. Saeb

    2016-01-01

    Full Text Available Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.

  4. Die Another Day, James Bond's smoking over six decades.

    Science.gov (United States)

    Wilson, Nick; Tucker, Anne

    2016-09-01

    We aimed to examine smoking-related content in all 24 James Bond movies in the Eon Productions series from 1962 to 2015. There were favourable downward trends for any smoking by James Bond (p=0.015 for trend), and for tobacco-related spy-gadgetry (p=0.009). Around 20% of Bond's 60 sexual partners smoked in each decade, and most recently in 2012. There were regular mentions of smoking risks to health (starting from 1967) and product placement of branded packs was present in two movies. Overall, the persisting smoking content remains problematic from a public health perspective, especially given the popularity of this movie series. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. James Madison and a Shift in Precipitation Seasonality

    Science.gov (United States)

    Druckenbrod, D. L.; Mann, M. E.; Stahle, D. W.; Cleaveland, M. K.; Therrell, M. D.; Shugart, H. H.

    2001-12-01

    An eighteen-year meteorological diary and tree ring data from James Madison's Montpelier plantation provide a consistent reconstruction of early summer and prior fall rainfall for the 18th Century Virginia piedmont. The Madison meteorological diary suggests a seasonal shift in monthly rainfall towards an earlier wet season relative to 20th Century norms. Furthermore, dendroclimatic reconstructions of early summer and prior fall rainfall reflect this shift in the seasonality of summer rainfall. The most pronounced early summer drought during the Madison diary period is presented as a case study. This 1792 drought occurs during one of the strongest El Niño events on record and is highlighted in the correspondence of James Madison.

  6. 1st International Symposium on Stress-Associated RNA Granules in Human Disease and Viral Infection

    Directory of Open Access Journals (Sweden)

    Bruce W. Banfield

    2014-09-01

    Full Text Available In recent years, important linkages have been made between RNA granules and human disease processes. On June 8-10 of this year, we hosted a new symposium, dubbed the 1st International Symposium on Stress-Associated RNA Granules in Human Disease and Viral Infection. This symposium brought together experts from diverse research disciplines ranging from cancer and neuroscience to infectious disease. This report summarizes speaker presentations and highlights current challenges in the field.

  7. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

    OpenAIRE

    Shroff, Geeta

    2016-01-01

    Case series Patient: Male, 42 ? Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue ? weakness in limbs Medication: ? Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause dela...

  8. Human genetics of infectious diseases: between proof of principle and paradigm

    OpenAIRE

    Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2009-01-01

    The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proo...

  9. 76 FR 7862 - Implementation of the James Zadroga 9/11 Health and Compensation Act of 2010 (Pub. L. 111-347)

    Science.gov (United States)

    2011-02-11

    ... brief introduction by Federal officials, followed by presentations from attendees who register to speak...), Department of Health and Human Services (HHS) announces a public meeting for receiving comments from the public on implementing the provisions of the James Zadroga 9/11 Health and Compensation Act of 2010 (Pub...

  10. Solar System Observations with the James Webb Space Telescope

    OpenAIRE

    Norwood, James; Hammel, Heidi; Milam, Stefanie; Stansberry, John; Lunine, Jonathan; Chanover, Nancy; Hines, Dean; Sonneborn, George; Tiscareno, Matthew; Brown, Michael; Ferruit, Pierre

    2014-01-01

    The James Webb Space Telescope will enable a wealth of new scientific investigations in the near- and mid-infrared, with sensitivity and spatial/spectral resolution greatly surpassing its predecessors. In this paper, we focus upon Solar System science facilitated by JWST, discussing the most current information available concerning JWST instrument properties and observing techniques relevant to planetary science. We also present numerous example observing scenarios for a wide variety of Solar...

  11. La racionalidad imperialista en la monumental obra de James Mill

    Directory of Open Access Journals (Sweden)

    Homero Cuevas

    2011-06-01

    Full Text Available Este ensayo, parte de un trabajo más extenso sobre la dominación internacional en la economía mundial, revisa los procesos más relevantes para el análisis teórico tomando como referencia La historia de la India británica de James Mill, obra que es un hito en este campo y es la base de todas las teorías posteriores

  12. The consequences of human actions on risks for infectious diseases: a review

    OpenAIRE

    Lindahl, Johanna F.; Grace, Delia

    2015-01-01

    The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating ...

  13. Human drivers of ecological and evolutionary dynamics in emerging and disappearing infectious disease systems.

    Science.gov (United States)

    Rogalski, Mary A; Gowler, Camden D; Shaw, Clara L; Hufbauer, Ruth A; Duffy, Meghan A

    2017-01-19

    Humans have contributed to the increased frequency and severity of emerging infectious diseases, which pose a significant threat to wild and domestic species, as well as human health. This review examines major pathways by which humans influence parasitism by altering (co)evolutionary interactions between hosts and parasites on ecological timescales. There is still much to learn about these interactions, but a few well-studied cases show that humans influence disease emergence every step of the way. Human actions significantly increase dispersal of host, parasite and vector species, enabling greater frequency of infection in naive host populations and host switches. Very dense host populations resulting from urbanization and agriculture can drive the evolution of more virulent parasites and, in some cases, more resistant host populations. Human activities that reduce host genetic diversity or impose abiotic stress can impair the ability of hosts to adapt to disease threats. Further, evolutionary responses of hosts and parasites can thwart disease management and biocontrol efforts. Finally, in rare cases, humans influence evolution by eradicating an infectious disease. If we hope to fully understand the factors driving disease emergence and potentially control these epidemics we must consider the widespread influence of humans on host and parasite evolutionary trajectories.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

  14. [A brief history of the natural causes of human disease].

    Science.gov (United States)

    Lips-Castro, Walter

    2015-01-01

    In the study of the causes of disease that have arisen during the development of humankind, one can distinguish three major perspectives: the natural, the supernatural, and the artificial. In this paper we distinguish the rational natural causes of disease from the irrational natural causes. Within the natural and rational causal approaches of disease, we can highlight the Egyptian theory of putrid intestinal materials called "wechdu", the humoral theory, the atomistic theory, the contagious theory, the cellular theory, the molecular (genetic) theory, and the ecogenetic theory. Regarding the irrational, esoteric, and mystic causal approaches to disease, we highlight the astrological, the alchemical, the iatrochemical, the iatromechanical, and others (irritability, solidism, brownism, and mesmerism).

  15. Human papillomavirus vaccine uptake among individuals with systemic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Candace H Feldman

    Full Text Available The human papillomavirus (HPV vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients.Using a U.S. insurance claims database (2006-2012, we identified individuals 9-26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date. We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11-26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization.We identified 5,642 patients 9-26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9. We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1. Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77-0.98 compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83-1.26. The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts.In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk.

  16. Human Papillomavirus Vaccine Uptake among Individuals with Systemic Inflammatory Diseases

    Science.gov (United States)

    Feldman, Candace H.; Hiraki, Linda T.; Lii, Huichuan; Seeger, John D.; Kim, Seoyoung C.

    2015-01-01

    Objectives The human papillomavirus (HPV) vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID) who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients. Methods Using a U.S. insurance claims database (2006–2012), we identified individuals 9–26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date). We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11–26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization. Results We identified 5,642 patients 9–26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9). We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1). Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77–0.98) compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83–1.26). The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts. Conclusions In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk. PMID:25692470

  17. Epidemiological studies on Johne’s disease in ruminants and Crohn’s disease in humans in Egypt

    Directory of Open Access Journals (Sweden)

    A. Fawzy

    2013-12-01

    Full Text Available The correlation between Johne’s disease (JD and Crohn’s disease (CD in Egypt was investigated. A total of 371 human and 435 animal sera were collected from the same Egyptian governorates that had a known history of paratuberculosis infection and were subjected to screening for paratuberculosis using ELISA to assess the human/animal risk at a single time point. Five CD patients and five JD clinically infected dairy cattle were also included. Out of 435 animal serum samples, 196 (45.2% were MAP-ELISA positive. Twenty three (6.1% out of 371 human serum samples were MAP-ELISA positive, while 37 (9.9% were positive for anti-Saccharomyces cerevisiae antibodies (ASCA ELISAs. There was a very poor agreement between human MAP and ASCA ELISAs (0.036 by kappa statistics. The prevalence of MAP antibodies among humans is clearly lower than in animals. In conclusion there is an increase in Johne’s disease incidence in animals and a very weak relationship between MAP and Crohn’s disease in humans in Egypt.

  18. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

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    Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

    2014-11-18

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

  19. Best Practices for Preventing Vector-Borne Diseases in Dogs and Humans.

    Science.gov (United States)

    Dantas-Torres, Filipe; Otranto, Domenico

    2016-01-01

    Vector-borne diseases constitute a diversified group of illnesses, which are caused by a multitude of pathogens transmitted by arthropod vectors, such as mosquitoes, fleas, ticks, and sand flies. Proper management of these diseases is important from both human and veterinary medicine standpoints, given that many of these pathogens are transmissible to humans and dogs, which often live in close contact. In this review, we summarize the most important vector-borne diseases of dogs and humans and the best practices for their prevention. The control of these diseases would ultimately improve animal and human health and wellbeing, particularly in developing countries in the tropics, where the risk of these diseases is high and access to health care is poor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

    Science.gov (United States)

    Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

    2015-10-01

    Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

  1. Religious Experience and its Essentialism in William James and Ghazzali’s Views

    Directory of Open Access Journals (Sweden)

    Ahmad Ebadi

    2016-03-01

    religious experience and mystical experience can be identified. The article begins with an introduction to the nature of religious experience, perspective and context of the rise of religious experience and goes on to describe the religious experience from the perspectives of Ghazali and William James and will deal with the differences between religious and mystical experiences. The comparative study of the similarities and differences between the views constitutes the last part of this study. This comparative study can be examined from several perspectives: 1. Concurrence of the two thinkers in the fact that religious experience is indefinable: William James and Ghazali both believe that religious experience are neither falsifiable nor unfalsifiable. No adequate conception of mystical experience can be expressed in words. Mystical experience is immediate and direct and cannot be transferred to others. 2. The differences in the origin of mystical experiences: William James believes in the effectiveness of alcoholic drinks in the creation of gnostic status. Then mystical manners can be achieved through this way as well. Unlike al-Ghazali, who believes the apocalyptical condition is only dependent on the grace of God and human attempt plays no role in its occurrence. 3. The vicious circle in the theory of James: The criterion by which William James would test the truth of a Religious Experience is the vision and experience, while the truth of religious propositions depends on and metaphysical and rational statements and not empirical proofs. Therefor their truth must be proven elsewhere. As a result, the only way to prove is the self-dependent criterion which will lead to a vicious circle. 4. Believing in the essentiality of religious experience: In this approach, sides and dimensions of religion are reduced to just one dimension and that is the essentiality of religious experience. From the perspective of William James, religious experience is the essence of religion in the

  2. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    Directory of Open Access Journals (Sweden)

    He Liu

    2016-01-01

    Full Text Available Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors.

  3. Mitochondrial DNA sequence variation in human evolution and disease.

    Science.gov (United States)

    Wallace, D C

    1994-09-13

    Germ-line and somatic mtDNA mutations are hypothesized to act together to shape our history and our health. Germ-line mtDNA mutations, both ancient and recent, have been associated with a variety of degenerative diseases. Mildly to moderately deleterious germ-line mutations, like neutral polymorphisms, have become established in the distant past through genetic drift but now may predispose certain individuals to late-onset degenerative diseases. As an example, a homoplasmic, Caucasian, tRNA(Gln) mutation at nucleotide pair (np) 4336 has been observed in 5% of Alzheimer disease and Parkinson disease patients and may contribute to the multifactorial etiology of these diseases. Moderately to severely deleterious germ-line mutations, on the other hand, appear repeatedly but are eliminated by selection. Hence, all extant mutations of this class are recent and associated with more devastating diseases of young adults and children. Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. To the inherited mutations are added somatic mtDNA mutations which accumulate in random arrays within stable tissues. These mutations provide a molecular clock that measures our age and may cause a progressive decline in tissue energy output that could precipitate the onset of degenerative diseases in individuals harboring inherited deleterious mutations.

  4. Human genetics of infectious diseases: between proof of principle and paradigm.

    Science.gov (United States)

    Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2009-09-01

    The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proof of principle that infectious diseases may result from various types of inborn errors of immunity, the genetic determinism of most infectious diseases in most patients remains unclear. However, in the future, studies in human genetics are likely to establish a new paradigm for infectious diseases.

  5. How to become a top model: impact of animal experimentation on human Salmonella disease research.

    Science.gov (United States)

    Tsolis, Renée M; Xavier, Mariana N; Santos, Renato L; Bäumler, Andreas J

    2011-05-01

    Salmonella serotypes are a major cause of human morbidity and mortality worldwide. Over the past decades, a series of animal models have been developed to advance vaccine development, provide insights into immunity to infection, and study the pathogenesis of human Salmonella disease. The successive introduction of new animal models, each suited to interrogate previously neglected aspects of Salmonella disease, has ushered in important conceptual advances that continue to have a strong and sustained influence on the ideas driving research on Salmonella serotypes. This article reviews important milestones in the use of animal models to study human Salmonella disease and identify research needs to guide future work.

  6. Insights into the human gut microbiome and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Soumalya Sarkar

    2018-01-01

    Full Text Available The microbiome comprises all of the genetic materials within a microbiota. This can also be referred to as the metagenome of the microbiota. Dysbiosis, a change in the composition of the gut microbiota, has been associated with pathology, including cardiovascular diseases (CVDs. The recently discovered contribution of gut microbiota-derived molecules in the development of heart disease and its risk factors has significantly increased attention toward the connection between our gut and heart. The gut microbiome is virtually an endocrine organ, capable of contributing to and reacting to circulating signaling molecules within the host. Gut microbiota-host interactions occur through many pathways, including trimethylamine-N-oxide and short-chain fatty acids. These molecules and others have been linked to chronic kidney disease, atherosclerosis, and hypertension. Dysbiosis has been implicated in CVD as well as many aspects of obesity, hypertension, chronic kidney disease, and diabetes.

  7. An atlas of genetic correlations across human diseases and traits

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are t...

  8. 'Who is wise and understanding among you' (James 3: 13? An analysis of wisdom, eschatology and apocalypticism in the epistle of James

    Directory of Open Access Journals (Sweden)

    Patrick J. Hartin

    1997-12-01

    Full Text Available Three questions form the basis of this analysis of the relationship of the Epistle of James to the traditions of wisdom, eschatology and apocalypticism. What kind of traditions are involved in James? What is the world view of James? What audience or community is presupposed by this writing? Foremost is the connection that James demonstrates to the wisdom tradition evident in the Old Testament and extratestamental literature. In particular two types of wisdom tradition are noted in James: practical wisdom advice as expressed in short sayings, wisdom instructions and admonitions and reflection on the nature of wisdom (1:5-8; 2:1-7; and 3:13-18 as coming from God. Finally, the question of how much apocalyptic symbolism is evident in the eschatological world view of the epistle is addressed.

  9. Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

    International Nuclear Information System (INIS)

    Mostafalou, Sara; Abdollahi, Mohammad

    2013-01-01

    Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. - Highlights: ► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up

  10. Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Mostafalou, Sara; Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca

    2013-04-15

    Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. - Highlights: ► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up.

  11. Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

    Science.gov (United States)

    Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

    2015-04-01

    Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Annotating Diseases Using Human Phenotype Ontology Improves Prediction of Disease-Associated Long Non-coding RNAs.

    Science.gov (United States)

    Le, Duc-Hau; Dao, Lan T M

    2018-05-23

    Recently, many long non-coding RNAs (lncRNAs) have been identified and their biological function has been characterized; however, our understanding of their underlying molecular mechanisms related to disease is still limited. To overcome the limitation in experimentally identifying disease-lncRNA associations, computational methods have been proposed as a powerful tool to predict such associations. These methods are usually based on the similarities between diseases or lncRNAs since it was reported that similar diseases are associated with functionally similar lncRNAs. Therefore, prediction performance is highly dependent on how well the similarities can be captured. Previous studies have calculated the similarity between two diseases by mapping exactly each disease to a single Disease Ontology (DO) term, and then use a semantic similarity measure to calculate the similarity between them. However, the problem of this approach is that a disease can be described by more than one DO terms. Until now, there is no annotation database of DO terms for diseases except for genes. In contrast, Human Phenotype Ontology (HPO) is designed to fully annotate human disease phenotypes. Therefore, in this study, we constructed disease similarity networks/matrices using HPO instead of DO. Then, we used these networks/matrices as inputs of two representative machine learning-based and network-based ranking algorithms, that is, regularized least square and heterogeneous graph-based inference, respectively. The results showed that the prediction performance of the two algorithms on HPO-based is better than that on DO-based networks/matrices. In addition, our method can predict 11 novel cancer-associated lncRNAs, which are supported by literature evidence. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Disease induction by human microbial pathogens in plant-model systems: potential, problems and prospects.

    Science.gov (United States)

    van Baarlen, Peter; van Belkum, Alex; Thomma, Bart P H J

    2007-02-01

    Relatively simple eukaryotic model organisms such as the genetic model weed plant Arabidopsis thaliana possess an innate immune system that shares important similarities with its mammalian counterpart. In fact, some human pathogens infect Arabidopsis and cause overt disease with human symptomology. In such cases, decisive elements of the plant's immune system are likely to be targeted by the same microbial factors that are necessary for causing disease in humans. These similarities can be exploited to identify elementary microbial pathogenicity factors and their corresponding targets in a green host. This circumvents important cost aspects that often frustrate studies in humans or animal models and, in addition, results in facile ethical clearance.

  14. Disease modeling using human induced pluripotent stem cells: lessons from the liver.

    Science.gov (United States)

    Gieseck, Richard L; Colquhoun, Jennifer; Hannan, Nicholas R F

    2015-01-01

    Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  15. [Oral microbiota: a promising predictor of human oral and systemic diseases].

    Science.gov (United States)

    Xin, Xu; Junzhi, He; Xuedong, Zhou

    2015-12-01

    A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.

  16. Human Embryonic Stem Cell Therapy in Crohn’s Disease: A Case Report

    Science.gov (United States)

    Shroff, Geeta

    2016-01-01

    Patient: Male, 21 Final Diagnosis: Crohn’s disease Symptoms: Intolerance to specific foods • abdominal pain and diarrhea Medication: Human embryonic stem cell therapy Clinical Procedure: Human embryonic stem cell transplantation Specialty: Gastroenterology Objective: Unusual or unexpected effect of treatment Background: Crohn’s disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565 000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn’s disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn’s disease. Case Report: A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Conclusions: Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn’s disease. PMID:26923312

  17. Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

    Science.gov (United States)

    Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

    2013-01-01

    Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

  18. Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond.

    Science.gov (United States)

    Liu, Chun; Oikonomopoulos, Angelos; Sayed, Nazish; Wu, Joseph C

    2018-03-08

    The advent of human induced pluripotent stem cells (iPSCs) presents unprecedented opportunities to model human diseases. Differentiated cells derived from iPSCs in two-dimensional (2D) monolayers have proven to be a relatively simple tool for exploring disease pathogenesis and underlying mechanisms. In this Spotlight article, we discuss the progress and limitations of the current 2D iPSC disease-modeling platform, as well as recent advancements in the development of human iPSC models that mimic in vivo tissues and organs at the three-dimensional (3D) level. Recent bioengineering approaches have begun to combine different 3D organoid types into a single '4D multi-organ system'. We summarize the advantages of this approach and speculate on the future role of 4D multi-organ systems in human disease modeling. © 2018. Published by The Company of Biologists Ltd.

  19. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients

    Directory of Open Access Journals (Sweden)

    Meng-Lu Liu

    2016-01-01

    Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  20. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  1. Discovering and Developing Successful Cardiovascular Therapeutics: A Conversation With James N. Topper, MD, PhD.

    Science.gov (United States)

    Topper, James N; Rutherford, John D

    2016-11-15

    Dr James (also known as Jamie) N. Topper, MD, PhD, serves as Managing General Partner at Frazier Healthcare Partners, where he leads the Life Science Venture practice. In 2011, and 2016, he was named to the Midas List of leading venture capitalists, and, in 2013, he was recognized by Forbes as one of the top 10 healthcare investors. He has >25 years of experience working with entrepreneurs to found and build successful therapeutics-focused companies. Dr Topper holds a BS from the University of Michigan. He received an MD and PhD (in biophysics) from Stanford University School of Medicine. He completed postgraduate training in internal medicine and cardiovascular disease at the Brigham and Women's Hospital in Boston and is board certified in both disciplines. © 2016 American Heart Association, Inc.

  2. Interstitial cells of Cajal in human gut and gastrointestinal disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J

    1999-01-01

    This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their fun......This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective...

  3. Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...Heterogeneity in Metabolic Disease Using Single- Cell RNA-Seq 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Linus Tzu-Yen...ABSTRACT We have developed a robust protocol to generate single cell transcriptional profiles from subcutaneous adipose tissue samples of both human

  4. Human Chagas Disease and Migration in the Context of Globalization: Some Particular Aspects

    Directory of Open Access Journals (Sweden)

    João Carlos Pinto Dias

    2013-01-01

    Full Text Available Human Chagas disease originated in Latin America, being spread around the world in relation with multiple bioecological, sociocultural, and political factors. The process of the disease production and dispersion is discussed, emphasizing the human migration and correlated aspects, in the context of globalization. Positive and negative consequences concern the future of this trypanosomiasis, mainly in terms of the ecologic and sociopolitical characteristics of the endemic and nonendemic countries.

  5. Soil, grain and water chemistry in relation to human selenium responsive diseases in Enshi District, China

    OpenAIRE

    Fordyce, F.M.; Zhang, Guangdi; Green, K.; Xinping, Liu

    2000-01-01

    Selenium deficiency (Keshan Disease) and toxicity diseases in humans occur within 20 km of each other in Enshi District in China and have been linked to environmental levels of Se. Low concentrations of Se are associated with Jurassic siltstones and sandstones, whereas high concentrations occur in areas underlain by Permian carbonaceous strata. Although these broad relationships between Se in the environment and the human population have been established previously, not all villages underlain...

  6. Diseases of Poverty and Lifestyle, Well-Being and Human Development

    OpenAIRE

    Singh, Ajai R.; Singh, Shakuntala A.

    2008-01-01

    The problems of the haves differ substantially from those of the have-nots. Individuals in developing societies have to fight mainly against infectious and communicable diseases, while in the developed world the battles are mainly against lifestyle diseases. Yet, at a very fundamental level, the problems are the same-the fight is against distress, disability, and premature death; against human exploitation and for human development and self-actualisation; against the callousness to critical c...

  7. Bollasina Receives 2013 James R. Holton Junior Scientist Award: Response

    Science.gov (United States)

    Bollasina, Massimo A.

    2014-08-01

    I am deeply honored to have been selected as this year's recipient of the James R. Holton Junior Scientist Award, and I receive it with heartfelt gratitude and humility. I clearly remember Peter Webster's call announcing the amazing news and how I literally remained speechless and overwhelmed. I would like to express my sincere appreciation to the Atmospheric Sciences section of AGU and the members of the award committee. I am even more appreciative to have been presented this award handed by two outstanding scientists—Peter Webster and Bill Lau—who have remarkably contributed to our understanding of the Asian monsoon and tropical climate, my area of expertise.

  8. James Van Allen The First Eight Billion Miles

    CERN Document Server

    Foerstner, Abigail

    2009-01-01

    Astrophysicist and space pioneer James Van Allen (1914-2006), for whom the Van Allen radiation belts were named, was among the principal scientific investigators for twenty-four space missions, including Explorer I in 1958, the first successful U.S. satellite; Mariner 2's 1962 flyby of Venus, the first successful mission to another planet; and the 1970's Pioneer 10 and Pioneer 11, missions that surveyed Jupiter and Saturn. Abigail Foerstner blends space science, drama, military agenda's, cold war politics, and the events of Van Allen's lengthy career to create the first biography of this highl

  9. James Baldwin: Biographical Dispatches on a Freedom Writer

    Directory of Open Access Journals (Sweden)

    Phillip Luke Sinitiere

    2016-12-01

    Full Text Available This essay presents the idea of James Baldwin as a freedom writer, the organizing idea of my biography in progress. As a freedom writer, Baldwin was a revolutionary intellectual, an essayist and novelist committed unfailingly to the realization of racial justice, interracial political equality, and economic democracy. While the book is still in process, this short essay narrates autobiographically how I came to meet and know Baldwin’s work, explains in critical fashion my work in relation to existing biographies, and reflects interpretively my thoughts-in- progress on this fascinating and captivating figure of immense historical and social consequence.

  10. Compensation and translation: James Ellroy’s White Jazz

    Directory of Open Access Journals (Sweden)

    Daria Protopopescu

    2008-01-01

    Full Text Available The current paper explores the Romanian translation of James Ellroy’s text “White Jazz”, with a view to explaining away the translator’s choices. The main issues at hand are the solutions provided for the ellipsis present throughout the novel and the slang used by the author, which is typical of L.A.’s ’60’s. The paper provides theoretical data supporting the translator’s choice of rendering certain slang expressions by paraphrase, explanation or even coinage of new words. We also look into how much has been compensated for and what was lost during the process of translation.

  11. Just how literal is the King James Version?

    OpenAIRE

    Jan (JH) Kroeze; Manie (CM) van den Heever; Bertus (AJ) van Rooy

    2010-01-01

    Many scholars have the perception that the King James Version (KJV) is a literal translation. However, it is not so easy to define the concept of "literal translation". The simplest definition may be to regard it as word-for-word translation. However, when one compares the KJV carefully with the original Hebrew Bible, there are numerous instances where lexical items are changed to adapt the idiom to that of the target language. In this article, a measuring instrument will be proposed and u...

  12. Thomas James Walker (1835-1916): Surgeon and general practitioner.

    Science.gov (United States)

    Thomas, Martyn

    2018-02-01

    Thomas James Walker was a surgeon and general practitioner who worked in the city of Peterborough at a time when there were changes and innovations in the practice of medicine. After training in medicine and surgery at Edinburgh University, he qualified in London in 1857. He was a pioneer of laryngoscopy. He played an important role in introducing antiseptic surgery to the Peterborough Infirmary and was instrumental in the development of the operating theatre which opened in 1894. He was a philanthropist and collector of Roman and Saxon artefacts. In 1915, he was recognized as an outstanding member of the Peterborough community when he was offered the Freedom of the City.

  13. Kynurenine Pathway Metabolites in Humans: Disease and Healthy States

    Directory of Open Access Journals (Sweden)

    Yiquan Chen

    2009-01-01

    Full Text Available Tryptophan is an essential amino acid that can be metabolised through different pathways, a major route being the kynurenine pathway. The first enzyme of the pathway, indoleamine-2,3-dioxygenase, is strongly stimulated by inflammatory molecules, particularly interferon gamma. Thus, the kynurenine pathway is often systematically up-regulated when the immune response is activated. The biological significance is that 1 the depletion of tryptophan and generation of kynurenines play a key modulatory role in the immune response; and 2 some of the kynurenines, such as quinolinic acid, 3-hydroxykynurenine and kynurenic acid, are neuroactive. The kynurenine pathway has been demonstrated to be involved in many diseases and disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found. This review compiles most of these studies and provides an overview of how the kynurenine pathway might be contributing to disease development, and the concentrations of tryptophan and kynurenines in the serum, cerebrospinal fluid and brain tissues in control and patient subjects.

  14. Linking disease associations with regulatory information in the human genome

    KAUST Repository

    Schaub, M. A.; Boyle, A. P.; Kundaje, A.; Batzoglou, S.; Snyder, M.

    2012-01-01

    Genome-wide association studies have been successful in identifying single nucleotide polymorphisms (SNPs) associated with a large number of phenotypes. However, an associated SNP is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the SNPs that have a biological link with the phenotype. We have systematically investigated the association of multiple types of ENCODE data with disease-associated SNPs and show that there is significant enrichment for functional SNPs among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated SNPs are used. We propose an approach that integrates multiple types of functional data generated by the ENCODE Consortium to help identify "functional SNPs" that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80% of all previously reported associations. We show that for most associations, the functional SNP most strongly supported by experimental evidence is a SNP in linkage disequilibrium with the reported association rather than the reported SNP itself. Our results show that the experimental data sets generated by the ENCODE Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.

  15. Emerging human infectious diseases: anthroponoses, zoonoses, and sapronoses

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk

    2003-01-01

    Roč. 9, č. 3 (2003), s. 403-404 ISSN 1080-6040 R&D Projects: GA AV ČR KSK6005114 Keywords : zoonoses Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 5.340, year: 2003 http://www.cdc.gov.ncidod/EID/vol9no3/02-0208-app.htm

  16. Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

    Science.gov (United States)

    Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.

    2014-01-01

    Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (pLyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099

  17. Effects of Forest Fragmentation on Human Risk of Lyme Disease

    Science.gov (United States)

    Percent forest-herbaceous edge repeatedly explained most of the variability in reported Lyme disease rates within a rural-to-urban study gradient across central Maryland and southeastern Pennsylvania. A one-percent increase in forest-herbaceous edge was associated with an increas...

  18. Positions of human dwellings affect few tropical diseases near ...

    African Journals Online (AJOL)

    user

    for the sandflies which is the vector of visceral leishmaniasis. It seems that the effect of microclimate was not on the considerations of villagers to build their dwellings as the very dense of date palms trees, vegetable farms and irrigation canals which are a determinant factors in the prevalence of diseases. Some dwellings ...

  19. Linking disease associations with regulatory information in the human genome

    KAUST Repository

    Schaub, M. A.

    2012-09-01

    Genome-wide association studies have been successful in identifying single nucleotide polymorphisms (SNPs) associated with a large number of phenotypes. However, an associated SNP is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the SNPs that have a biological link with the phenotype. We have systematically investigated the association of multiple types of ENCODE data with disease-associated SNPs and show that there is significant enrichment for functional SNPs among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated SNPs are used. We propose an approach that integrates multiple types of functional data generated by the ENCODE Consortium to help identify "functional SNPs" that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80% of all previously reported associations. We show that for most associations, the functional SNP most strongly supported by experimental evidence is a SNP in linkage disequilibrium with the reported association rather than the reported SNP itself. Our results show that the experimental data sets generated by the ENCODE Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.

  20. Teaching Methods in Nutrition: Free Radicals, Antioxidants, and Human Disease.

    Science.gov (United States)

    Janowiak, John J.

    This article presents a teaching methodology for free radical theory and discusses the role of antioxidants in human health. Free radicals are a normal byproduct of respiration, which allows the body to use oxygen, liberate energy, and dispose of harmful substances. The body's antioxidants and nutritional antioxidants quench most of the free…

  1. Integrated Human and Animal Disease Control for Tanzanian ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The research focuses on two agro-ecological zones of the cattle corridor in Tanzania - Ngorongoro and Kibaha/Kilosa districts - and will be led by a regional scientific network, the ... They will look at interactions between human and animal health, environmental change, gender, and other socio-economic conditions.

  2. Food safety. [chemical contaminants and human toxic diseases

    Science.gov (United States)

    Pier, S. M.; Valentine, J. L.

    1975-01-01

    Illness induced by unsafe food is a problem of great public health significance. This study relates exclusively to the occurrence of chemical agents which will result in food unsafe for human consumption since the matter of food safety is of paramount importance in the mission and operation of the manned spacecraft program of the National Aeronautics and Space Administration.

  3. The role of airborne mineral dusts in human disease

    Science.gov (United States)

    Morman, Suzette A.; Plumlee, Geoffrey S.

    2013-01-01

    Exposure to fine particulate matter (PM) is generally acknowledged to increase risk for human morbidity and mortality. However, particulate matter (PM) research has generally examined anthropogenic (industry and combustion by-products) sources with few studies considering contributions from geogenic PM (produced from the Earth by natural processes, e.g., volcanic ash, windborne ash from wildfires, and mineral dusts) or geoanthropogenic PM (produced from natural sources by processes that are modified or enhanced by human activities, e.g., dusts from lakebeds dried by human removal of water, dusts produced from areas that have undergone desertification as a result of human practices). Globally, public health concerns are mounting, related to potential increases in dust emission from climate related changes such as desertification and the associated long range as well as local health effects. Recent epidemiological studies have identified associations between far-traveled dusts from primary sources and increased morbidity and mortality in Europe and Asia. This paper provides an outline of public health research and history as it relates to naturally occurring inorganic mineral dusts. We summarize results of current public health research and describe some of the many challenges related to understanding health effects from exposures to dust aerosols.

  4. Human rabies: Still a neglected preventable disease in Nigeria | Eke ...

    African Journals Online (AJOL)

    Background/Objectives: Adequate surveillance and monitoring of dog bite incidents are veritable tools in the determination of the epidemiology of human rabies infections. There is a paucity of data with regards to rabies in Nigeria. Hence, this study was aimed at describing the pattern and outcomes of dog bites and rabies ...

  5. North Atlantic weather oscillation and human infectious diseases in the Czech Republic, 1951-2003

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk

    2005-01-01

    Roč. 20, č. 3 (2005), s. 263-270 ISSN 0393-2990 R&D Projects: GA ČR(CZ) GA206/03/0726 Institutional research plan: CEZ:AV0Z60930519 Keywords : climate change * cluster analysis * human infectious diseases Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 1.361, year: 2005

  6. Barcoding heat shock proteins to human diseases : looking beyond the heat shock response

    NARCIS (Netherlands)

    Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H.

    There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR) - and thus generally restoring the disturbed protein homeostasis associated with such diseases - has often been suggested as a

  7. Modelling the influence of human behaviour on the spread of infectious diseases: a review.

    Science.gov (United States)

    Funk, Sebastian; Salathé, Marcel; Jansen, Vincent A A

    2010-09-06

    Human behaviour plays an important role in the spread of infectious diseases, and understanding the influence of behaviour on the spread of diseases can be key to improving control efforts. While behavioural responses to the spread of a disease have often been reported anecdotally, there has been relatively little systematic investigation into how behavioural changes can affect disease dynamics. Mathematical models for the spread of infectious diseases are an important tool for investigating and quantifying such effects, not least because the spread of a disease among humans is not amenable to direct experimental study. Here, we review recent efforts to incorporate human behaviour into disease models, and propose that such models can be broadly classified according to the type and source of information which individuals are assumed to base their behaviour on, and according to the assumed effects of such behaviour. We highlight recent advances as well as gaps in our understanding of the interplay between infectious disease dynamics and human behaviour, and suggest what kind of data taking efforts would be helpful in filling these gaps.

  8. DNA replication stress: from molecular mechanisms to human disease.

    Science.gov (United States)

    Muñoz, Sergio; Méndez, Juan

    2017-02-01

    The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of "replicative stress" (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.

  9. Acetylome in Human Fibroblasts From Parkinson's Disease Patients

    Directory of Open Access Journals (Sweden)

    Sokhna M. S. Yakhine-Diop

    2018-04-01

    Full Text Available Parkinson's disease (PD is a multifactorial neurodegenerative disorder. The pathogenesis of this disease is associated with gene and environmental factors. Mutations in leucine-rich repeat kinase 2 (LRRK2 are the most frequent genetic cause of familial and sporadic PD. Moreover, posttranslational modifications, including protein acetylation, are involved in the molecular mechanism of PD. Acetylation of lysine proteins is a dynamic process that is modulated in PD. In this descriptive study, we characterized the acetylated proteins and peptides in primary fibroblasts from idiopathic PD (IPD and genetic PD harboring G2019S or R1441G LRRK2 mutations. Identified acetylated peptides are modulated between individuals' groups. Although acetylated nuclear proteins are the most represented in cells, they are hypoacetylated in IPD. Results display that the level of hyperacetylated and hypoacetylated peptides are, respectively, enhanced in genetic PD and in IPD cells.

  10. Human Genetic Variation and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sun Ju Chung

    2010-05-01

    Full Text Available Parkinson’s disease (PD is a chronic neurodegenerative disorder with multifactorial etiology. In the past decade, the genetic causes of monogenic forms of familial PD have been defined. However, the etiology and pathogenesis of the majority of sporadic PD cases that occur in outbred populations have yet to be clarified. The recent development of resources such as the International HapMap Project and technological advances in high-throughput genotyping have provided new basis for genetic association studies of common complex diseases, including PD. A new generation of genome-wide association studies will soon offer a potentially powerful approach for mapping causal genes and will likely change treatment and alter our perception of the genetic determinants of PD. However, the execution and analysis of such studies will require great care.

  11. Application of high-throughput sequencing in understanding human oral microbiome related with health and disease

    OpenAIRE

    Chen, Hui; Jiang, Wen

    2014-01-01

    The oral microbiome is one of most diversity habitat in the human body and they are closely related with oral health and disease. As the technique developing,, high throughput sequencing has become a popular approach applied for oral microbial analysis. Oral bacterial profiles have been studied to explore the relationship between microbial diversity and oral diseases such as caries and periodontal disease. This review describes the application of high-throughput sequencing for characterizati...

  12. Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes

    Directory of Open Access Journals (Sweden)

    Duda Marlena

    2012-11-01

    Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better

  13. Serum inflammatory mediators as markers of human Lyme disease activity.

    Directory of Open Access Journals (Sweden)

    Mark J Soloski

    Full Text Available Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005 in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG, CXCL10 (IP-10 and CCL19 (MIP3B were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively. There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01 and the decrease correlates with chemokine levels (p = 0.0375. The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

  14. The dopamine transporter: role in neurotoxicity and human disease

    International Nuclear Information System (INIS)

    Bannon, Michael J.

    2005-01-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  15. The dopamine transporter: role in neurotoxicity and human disease

    Energy Technology Data Exchange (ETDEWEB)

    Bannon, Michael J [Department of Psychiatry and Behavioral Neuroscience, Pharmacology, and Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2005-05-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  16. Human genetics of infectious diseases: Unique insights into immunological redundancy.

    Science.gov (United States)

    Casanova, Jean-Laurent; Abel, Laurent

    2018-04-01

    For almost any given human-tropic virus, bacterium, fungus, or parasite, the clinical outcome of primary infection is enormously variable, ranging from asymptomatic to lethal infection. This variability has long been thought to be largely determined by the germline genetics of the human host, and this is increasingly being demonstrated to be the case. The number and diversity of known inborn errors of immunity is continually increasing, and we focus here on autosomal and X-linked recessive traits underlying complete deficiencies of the encoded protein. Schematically, four types of infectious phenotype have been observed in individuals with such deficiencies, each providing information about the redundancy of the corresponding human gene, in terms of host defense in natural conditions. The lack of a protein can confer vulnerability to a broad range of microbes in most, if not all patients, through the disruption of a key immunological component. In such cases, the gene concerned is of low redundancy. However, the lack of a protein may also confer vulnerability to a narrow range of microbes, sometimes a single pathogen, and not necessarily in all patients. In such cases, the gene concerned is highly redundant. Conversely, the deficiency may be apparently neutral, conferring no detectable predisposition to infection in any individual. In such cases, the gene concerned is completely redundant. Finally, the lack of a protein may, paradoxically, be advantageous to the host, conferring resistance to one or more infections. In such cases, the gene is considered to display beneficial redundancy. These findings reflect the current state of evolution of humans and microbes, and should not be considered predictive of redundancy, or of a lack of redundancy, in the distant future. Nevertheless, these observations are of potential interest to present-day biologists testing immunological hypotheses experimentally and physicians managing patients with immunological or infectious

  17. James Weldon Johnson and the Speech Lab Recordings

    Directory of Open Access Journals (Sweden)

    Chris Mustazza

    2016-03-01

    Full Text Available On December 24, 1935, James Weldon Johnson read thirteen of his poems at Columbia University, in a recording session engineered by Columbia Professor of Speech George W. Hibbitt and Barnard colleague Professor W. Cabell Greet, pioneers in the field that became sociolinguistics. Interested in American dialects, Greet and Hibbitt used early sound recording technologies to preserve dialect samples. In the same lab where they recorded T.S. Eliot, Gertrude Stein, and others, James Weldon Johnson read a selection of poems that included several from his seminal collection God’s Trombones and some dialect poems. Mustazza has digitized these and made them publicly available in the PennSound archive. In this essay, Mustazza contextualizes the collection, considering the recordings as sonic inscriptions alongside their textual manifestations. He argues that the collection must be heard within the frames of its production conditions—especially its recording in a speech lab—and that the sound recordings are essential elements in an hermeneutic analysis of the poems. He reasons that the poems’ original topics are reframed and refocused when historicized and contextualized within the frame of The Speech Lab Recordings.

  18. Film-Induced Tourism in the Way of Saint James

    Directory of Open Access Journals (Sweden)

    Lucrezia Lopez

    2015-03-01

    Full Text Available This research paper proposes an analytical approach to the study of the phenomenon of the film-induced pilgrimage tourism, along one of the most historical and relevant European cultural route: the Way of St. James or Camino de Santiago.In the present study, and in order to point out the relation between film broadcast and film-induced tourism, we combine the review of the Jacobean cinema with the statistical analysis of the pilgrims arrived to Santiago de Compostela during the last decade. So, our main aim is to analyse the repercussion of the Jacobean Cinema in the attractiveness of the Way of St. James as tourism destination. We take into consideration the role of the film producers and we also ponder on the marketing policies of the Autonomous Community, which are aimed at promoting the pilgrim’s routes, the Cathedral and the city of Santiago de Compostela. The cinema has played a less important role until now, in comparison with the impact of travel guides and the Jacobean literature, but it is increasing its impact in the international tourism markets. Recently, the American film The Way can be considered to be the first promoter of the film-induced tourism, because the arrivals of pilgrims from USA have been increased after the broadcast of this film since 2010.

  19. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert

    2015-06-08

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  20. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    Science.gov (United States)

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-06-01

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  1. Quadrivalent human papillomavirus vaccination in boys and risk of autoimmune diseases, neurological diseases and venous thromboembolism

    DEFF Research Database (Denmark)

    Frisch, Morten; Besson, Andréa; Clemmensen, Kim Katrine Bjerring

    2018-01-01

    following HPV vaccination in this group. We investigated if quadrivalent HPV (qHPV) vaccination of 10-17-year-old boys is associated with any unusual risk of autoimmune diseases, neurological diseases or venous thromboembolism. Methods: We conducted a national cohort study of 568 410 boys born in Denmark...... 1988-2006 and followed for 4 million person-years during 2006-16, using nationwide registers to obtain individual-level information about received doses of the qHPV vaccine and hospital records for 39 autoimmune diseases, 12 neurological diseases and venous thromboembolism. For each outcome, we...... estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) according to qHPV vaccination status. Results: Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10-17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96; 95% CI...

  2. Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection

    Directory of Open Access Journals (Sweden)

    J. Njeru

    2016-08-01

    Full Text Available Abstract Background Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. Methods A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. Results The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B. abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine

  3. Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection.

    Science.gov (United States)

    Njeru, J; Wareth, G; Melzer, F; Henning, K; Pletz, M W; Heller, R; Neubauer, H

    2016-08-22

    Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B.) abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine disease underreporting. We found no studies of disease

  4. Metabolomics in plants and humans: applications in the prevention and diagnosis of diseases.

    Science.gov (United States)

    Gomez-Casati, Diego F; Zanor, Maria I; Busi, María V

    2013-01-01

    In the recent years, there has been an increase in the number of metabolomic approaches used, in parallel with proteomic and functional genomic studies. The wide variety of chemical types of metabolites available has also accelerated the use of different techniques in the investigation of the metabolome. At present, metabolomics is applied to investigate several human diseases, to improve their diagnosis and prevention, and to design better therapeutic strategies. In addition, metabolomic studies are also being carried out in areas such as toxicology and pharmacology, crop breeding, and plant biotechnology. In this review, we emphasize the use and application of metabolomics in human diseases and plant research to improve human health.

  5. Advances in metal-induced oxidative stress and human disease

    International Nuclear Information System (INIS)

    Jomova, Klaudia; Valko, Marian

    2011-01-01

    Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha

  6. Human organoids: a model system for intestinal diseases

    OpenAIRE

    Wiegerinck, C.L.

    2015-01-01

    You are what you eat. A common saying that indicates that your physical or mental state can be influenced by your choice of food. Unfortunately, not all people have the luxury to choose what to eat; this can be related to place of birth, social, economic state, or the physical inability of the diseased intestine to take up certain food. A cell layer, the epithelium, covers the intestine, and harbors the main functions of the intestine: uptake, digestion of food, and a barrier against unwanted...

  7. X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

    Science.gov (United States)

    Chia, L S; Thompson, J E; Moscarello, M A

    1984-09-05

    Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

  8. Trends in population-based studies of human genetics in infectious diseases.

    Science.gov (United States)

    Rowell, Jessica L; Dowling, Nicole F; Yu, Wei; Yesupriya, Ajay; Zhang, Lyna; Gwinn, Marta

    2012-01-01

    Pathogen genetics is already a mainstay of public health investigation and control efforts; now advances in technology make it possible to investigate the role of human genetic variation in the epidemiology of infectious diseases. To describe trends in this field, we analyzed articles that were published from 2001 through 2010 and indexed by the HuGE Navigator, a curated online database of PubMed abstracts in human genome epidemiology. We extracted the principal findings from all meta-analyses and genome-wide association studies (GWAS) with an infectious disease-related outcome. Finally, we compared the representation of diseases in HuGE Navigator with their contributions to morbidity worldwide. We identified 3,730 articles on infectious diseases, including 27 meta-analyses and 23 GWAS. The number published each year increased from 148 in 2001 to 543 in 2010 but remained a small fraction (about 7%) of all studies in human genome epidemiology. Most articles were by authors from developed countries, but the percentage by authors from resource-limited countries increased from 9% to 25% during the period studied. The most commonly studied diseases were HIV/AIDS, tuberculosis, hepatitis B infection, hepatitis C infection, sepsis, and malaria. As genomic research methods become more affordable and accessible, population-based research on infectious diseases will be able to examine the role of variation in human as well as pathogen genomes. This approach offers new opportunities for understanding infectious disease susceptibility, severity, treatment, control, and prevention.

  9. Mechanistic modeling of aberrant energy metabolism in human disease

    Directory of Open Access Journals (Sweden)

    Vineet eSangar

    2012-10-01

    Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

  10. Borna disease virus and its role in the pathology of animals and humans

    Directory of Open Access Journals (Sweden)

    A. O. Mikheev

    2017-12-01

    Full Text Available Infectious diseases that are caused by numerous pathogenic microorganisms – bacteria, viruses, protozoa or fungi – can be transmitted from patients or carriers to healthy people or animals. A large group of infectious disease is caused by pathogens of animal infections – zoonoses. The issue of zoonoses is of great significance in human pathology and requires comprehensive study. This is of particular relevance to Ukraine, as the question of prevalence, level within the population and threats to human life and health from zoonoses, though highly important, has remained insufficiently studied. Information about many of these pathogens is absent in the existing scientific literature accessible in Ukraine – both veterinary and medical. This applies, in particular, to a causative agent of viral zoonoses the Borna disease virus or Bornavirus. For this purpose, an analysis of the literature concerning the role of the Bornavirus in the pathology of animals and humans was conducted. It is well known that a large number of pathogens of animal infections (zoonoses, including viral, pose a potential threat to human health. Among these potential threats is the Borna disease virus belonging to the family of Bornaviridae, order Mononegavirales. This order includes representatives of deadly human diseases like rabies (family Rhabdoviridae, Ebola virus (family Filoviridae and Nipah virus (family Paramyxoviridae. Borna virus disease affects mainly mammals, but can infect birds and even reptiles (Aspid bornavirus. It is established that Bornaviruses have a wide range of natural hosts (horses, sheeps, cats, bats and various birds, including domestic animals, which poses a potential threat to human health. This is evidenced by numerous, although contradictory, research into the role of the Borna disease virus in human pathologies such as schizophrenia, depression, prolonged fatigue syndrome, multiple sclerosis and others. Analysis of the literature clearly

  11. [Detection of human parvovirus B19, human bocavirus and human parvovirus 4 infections in blood samples among 95 patients with liver disease in Nanjing by nested PCR].

    Science.gov (United States)

    Tong, Rui; Zhou, Wei-Min; Liu, Xi-Jun; Wang, Yue; Lou, Yong-Liang; Tan, Wen-Jie

    2013-04-01

    To analyze the infection of human parvovirus B19, human bocavirus (HBoV) and human parvovirus 4 (PARV4) in blood samples among patients with liver disease in Nanjing by molecular detection. Nested PCR assays were designed and validated to detect B19, HBoV and PARV4, respectively. The assays were used to screen three parvoviruses in blood samples from 95 patients with different liver disease in Nanjing. The parvovirus infection was analyzed statistically. The detection limits were 10 copies of genomic DNA equivalents per reaction for each assays and the good specificity were observed. The frequency of B19 and HBoV were 2/95 (2.1%) and 9/95 (9.5%) in blood samples respectively. No PARV4 was detected. HBoV was detected in 3/5 patients with drug-induced hepatitis. Both B19 and HBoV infection were detected in blood from patients with liver disease.

  12. Using therapeutic cloning to fight human disease: a conundrum or reality?

    Science.gov (United States)

    Hall, Vanessa J; Stojkovic, Petra; Stojkovic, Miodrag

    2006-07-01

    The development and transplantation of autologous cells derived from nuclear transfer embryonic stem cell (NT-ESC) lines to treat patients suffering from disease has been termed therapeutic cloning. Human NT is still a developing field, with further research required to improve somatic cell NT and human embryonic stem cell differentiation to deliver safe and effective cell replacement therapies. Furthermore, the implications of transferring mitochondrial heteroplasmic cells, which may harbor aberrant epigenetic gene expression profiles, are of concern. The production of human NT-ESC lines also remains plagued by ethical dilemmas, societal concerns, and controversies. Recently, a number of alternate therapeutic strategies have been proposed to circumvent the moral implications surrounding human nuclear transfer. It will be critical to overcome these biological, legislative, and moral restraints to maximize the potential of this therapeutic strategy and to alleviate human disease.

  13. The human RNase MRP complex : composition, assembly and role in human disease

    NARCIS (Netherlands)

    Eenennaam, Hans van

    2002-01-01

    Not all RNA molecules in human cells are being translated into proteins. Some of them function in binding proteins, thereby forming so-called RNA-protein complexes. The RNase MRP complex is an example of such an RNA-protein complex. In this thesis two new protein components of the human RNase MRP

  14. Targeting ADAM12 in human disease: head, body or tail?

    DEFF Research Database (Denmark)

    Jacobsen, J; Wewer, U M

    2009-01-01

    ) and insulin-like growth factor receptor signaling. The body of the protein (consisting of the disintegrin, cysteine-rich, and EGF-like domains) is involved in contacts with the extracellular matrix and other cells through interactions with integrins and syndecans. Finally, the tail of the protein (consisting......ADAM12/meltrin alpha is a type I transmembrane multidomain protein involved in tumor progression and other severe diseases, including osteoarthritis, and as such could be considered as a potential drug target. In addition to protease activity, ADAM12 possesses cell binding and cell signaling...... properties. This functional trinity is reflected in the structure of ADAM12, which can be divided into head, body, and tail. The head of the protein (consisting of the pro and catalytic domains) mediates processing of growth factors and cytokines and has been implicated in epidermal growth factor (EGF...

  15. Climate change and Ixodes tick-borne diseases of humans.

    Science.gov (United States)

    Ostfeld, Richard S; Brunner, Jesse L

    2015-04-05

    The evidence that climate warming is changing the distribution of Ixodes ticks and the pathogens they transmit is reviewed and evaluated. The primary approaches are either phenomenological, which typically assume that climate alone limits current and future distributions, or mechanistic, asking which tick-demographic parameters are affected by specific abiotic conditions. Both approaches have promise but are severely limited when applied separately. For instance, phenomenological approaches (e.g. climate envelope models) often select abiotic variables arbitrarily and produce results that can be hard to interpret biologically. On the other hand, although laboratory studies demonstrate strict temperature and humidity thresholds for tick survival, these limits rarely apply to field situations. Similarly, no studies address the influence of abiotic conditions on more than a few life stages, transitions or demographic processes, preventing comprehensive assessments. Nevertheless, despite their divergent approaches, both mechanistic and phenomenological models suggest dramatic range expansions of Ixodes ticks and tick-borne disease as the climate warms. The predicted distributions, however, vary strongly with the models' assumptions, which are rarely tested against reasonable alternatives. These inconsistencies, limited data about key tick-demographic and climatic processes and only limited incorporation of non-climatic processes have weakened the application of this rich area of research to public health policy or actions. We urge further investigation of the influence of climate on vertebrate hosts and tick-borne pathogen dynamics. In addition, testing model assumptions and mechanisms in a range of natural contexts and comparing their relative importance as competing models in a rigorous statistical framework will significantly advance our understanding of how climate change will alter the distribution, dynamics and risk of tick-borne disease.

  16. The suggestion of common cause of disease, characteristics of human body, and medical treatment

    Directory of Open Access Journals (Sweden)

    Byung-Jun Cho

    2011-06-01

    Full Text Available Objectives & Methods: This suggestion was attempted to be elevated the recognition of common characteristics in disease. So, we performed to analyze the correlation of common cause of disease, characteristics of human body, and medical treatment. And the results are as follows. Results: 1. The cause of disease is consist of genetic factor, aging, habit, food of not good in health, weather, environment, deficit of the physical activity, stress and so on. 2. Generally, human has common and individual weakness. Individual weakness is appeared similar to the occurrence of volcano and lapse. 3. The correlation of disease and medical treatments is possible to explain using the quotation of the law of motion made by Isaac Newton, the great physicist. 4. When the process of the medical treatment was not progressed, the prognosis is determined by the correlation of the homeostasis(H' in human body and the homeostasis(H of disease. 5. The prognosis of disease is determined by the relationship between the energy of disease(F and medical treatment(F'. 6. The exact diagnosis is possible to predict the treatment sequence, and the facts that homeostasis in human body and disease, relationship between the energy of disease(F and medical treatment(F', action and reaction are important to determine the prognosis. 7. The careful observation of improving response and worsening action of disease becomes available for exact prognosis. Conclusion: The above described contents may be useful in clinical studies, and the concrete clinical reports about this will be made afterward.

  17. Rapidly progressive periodontal disease associated with human immunodeficiency virus

    International Nuclear Information System (INIS)

    Hezaim, K.A.; Javed, F.; Askar, A.; Rasheed, A.A.

    2012-01-01

    Severe periodontal inflammation with generalized dental plaque accumulation, spontaneous and severe gingival bleeding, fungal infection, and inter dental papillae necrosis are presented in a patient infected with human immunodeficiency virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on the gingival mucosa in both jaws. DNA testing was performed to identify the periodontopathogens. The patient had no signs or symptoms of acquired immunodeficiency syndrome. This case-report presents the massive periodontal destruction that occurred in a patient infected with HIV. Therefore, it is highly recommended that patients infected with HIV should be regularly monitored to aid in early detection and to provide proper management of periodontal inflammatory conditions to minimize its destruction. (author)

  18. Human Fascioliasis: A Re-emerging Disease in Upper Egypt

    Science.gov (United States)

    Mekky, Mohamed A.; Tolba, Mohammed; Abdel-Malek, Mohamed O.; Abbas, Wael A.; Zidan, Mohamed

    2015-01-01

    In recent years, the number of humans infected with Fasciola has risen rapidly. Diagnosis is based mainly on detection of eggs in stool analysis. The rate of infection in Egypt is unknown. In this retrospective study, we describe 23 cases of hepatic fascioliasis, and only 2 of these cases showed eggs in stools. The symptoms of infection, such as pyrexia of unknown origin, epigastric pain, and abdominal distension, were suggestive. Imaging techniques, including abdominal ultrasonography and computed tomography, were very helpful in detecting hepatic changes. An indirect hemagglutination assay proved to be of value for diagnosis. Treatment using a 2-day triclabendazole regimen cured the infection and signs of hepatic involvement disappeared. Combining both imaging techniques and laboratory tests is essential for diagnosis of fascioliasis in the early stage. PMID:25870421

  19. Human fascioliasis: a re-emerging disease in upper Egypt.

    Science.gov (United States)

    Mekky, Mohamed A; Tolba, Mohammed; Abdel-Malek, Mohamed O; Abbas, Wael A; Zidan, Mohamed

    2015-07-01

    In recent years, the number of humans infected with Fasciola has risen rapidly. Diagnosis is based mainly on detection of eggs in stool analysis. The rate of infection in Egypt is unknown. In this retrospective study, we describe 23 cases of hepatic fascioliasis, and only 2 of these cases showed eggs in stools. The symptoms of infection, such as pyrexia of unknown origin, epigastric pain, and abdominal distension, were suggestive. Imaging techniques, including abdominal ultrasonography and computed tomography, were very helpful in detecting hepatic changes. An indirect hemagglutination assay proved to be of value for diagnosis. Treatment using a 2-day triclabendazole regimen cured the infection and signs of hepatic involvement disappeared. Combining both imaging techniques and laboratory tests is essential for diagnosis of fascioliasis in the early stage. © The American Society of Tropical Medicine and Hygiene.

  20. Human rabies: still a neglected preventable disease in Nigeria.

    Science.gov (United States)

    Eke, C B; Omotowo, I B; Ukoha, O M; Ibe, B C

    2015-01-01

    Adequate surveillance and monitoring of dog bite incidents are veritable tools in the determination of the epidemiology of human rabies infections. There is a paucity of data with regards to rabies in Nigeria. Hence, this study was aimed at describing the pattern and outcomes of dog bites and rabies infections among patients presenting to University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. This was a 10-year (January 1, 2004 to December 31, 2013) observational retrospective study. Case definition of rabies was based on ICD 10 criteria, while relevant clinical data were retrieved from individual folders of registered victims using a semi-structured questionnaire. Data were analyzed using SPSS version 17.0 while the level of statistical significance was set at P cases of dog bites were reported during the period under review, of which 6 (4.0%) had confirmed rabies. Ninety-six (64.4%) cases presented more than 24 h after the bites. Majority of the offending dogs were stray dogs 86 (57.7%), which attacked their victims unprovoked, in 54.6% of cases. Furthermore, most of the bites were from dogs with unknown history of rabies vaccination 72 (52.3%), while the case fatality rate was 100%. All the cases of rabies reported were as a result of bites from stray dogs with unknown history of rabies vaccinations, and the outcome was 100% fatality in all cases. Efforts should be made to create and strengthen awareness campaigns on control of rabies infections through responsible dog ownership including their regular vaccinations as well as provision and use of prompt postexposure prophylaxis in human cases of dog bites at all levels of health care.

  1. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

    Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

  2. Genetic human prion disease modelled in PrP transgenic Drosophila.

    Science.gov (United States)

    Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

    2017-09-20

    Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

  3. Human Embryonic Stem Cell Therapy in Crohn's Disease: A Case Report.

    Science.gov (United States)

    Shroff, Geeta

    2016-02-29

    Crohn's disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565,000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn's disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn's disease. A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn's disease.

  4. New variant of Creutzfeldt-Jakob (vCJD) disease and other human prion diseases under epidemiological surveillance in Brazil

    OpenAIRE

    Gattás, Vera Lúcia; Lima Neto, Antonio Silva; Dimech, George Santiago; Mancini, Denise; Cantarino, Ligia Maria; Marins, José Ricardo Pio; Luna, Expedito José Albuquerque

    2007-01-01

    Abstract To increase the timeliness of detection of human cases of the new variant of Creutzfeldt-Jakob disease (vCJD) and to reduce the risk of transmission, the Brazilian Ministry of Health has established and standardized rules and control measures. These include the definition of criteria for suspect cases, reporting, monitoring, and control measures for illness prevention and transmission. Guidelines to be used by the team of health care staff were published and distributed to health wor...

  5. Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

    Science.gov (United States)

    Bergman, P; Seyedoleslami Esfahani, S; Engström, Y

    2017-01-01

    Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila. This review describes the current knowledge on Drosophila as a model for human diseases, with a special focus on innate immune-related disorders of the gut, lung, and skin. The discovery of antimicrobial peptides, the crucial role of Toll and Toll-like receptors, and the evolutionary conservation of signaling to the immune systems of both human and Drosophila are described in a historical perspective. Similarities and differences between human and Drosophila are discussed; current knowledge on receptors, signaling pathways, and effectors are reviewed, including antimicrobial peptides, reactive oxygen species, as well as autophagy. We also give examples of human diseases for which Drosophila appears to be a useful model. In addition, the limitations of the Drosophila model are mentioned. Finally, we propose areas for future research, which include using the Drosophila model for drug screening, as a validation tool for novel genetic mutations in humans and for exploratory research of microbiota-host interactions, with relevance for infection, wound healing, and cancer. © 2017 Elsevier Inc. All rights reserved.

  6. Human Genome Epidemiology : A scientific foundation for using genetic information to improve health and prevent disease

    Directory of Open Access Journals (Sweden)

    Stefania Boccia

    2005-03-01

    Full Text Available

    Human health is determined by the interplay of genetic factors and the environment. In this context the recent advances in human genomics are expected to play a central role in medicine and public health by providing genetic information for disease prediction and prevention.

    After the completion of the human genome sequencing, a fundamental step will be represented by the translation of these discoveries into meaningful actions to improve health and prevent diseases, and the field of epidemiology plays a central role in this effort. These are some of the issues addressed by Human Genome Epidemiology –A scientific foundation for using genetic information to improve health and prevent disease, a volume edited by Prof. M. Khoury, Prof. J. Little, Prof.W. Burke and published by Oxford university Press 2004.

    This book describes the important role that epidemiological methods play in the continuum from gene discovery to the development and application of genetic tests. The Authors calls this continuum human genome epidemiology (HuGE to denote an evolving field of inquiry that uses systematic applications of epidemiological methods to assess the impact of human genetic variation on health and disease.

    The book is divided into four sections and it is structured to allow readers to proceed systematically from the fundamentals of genome technology and discovery, to the epidemiological approaches, to gene characterisation, to the evaluation of genetic tests and their use in health services and public health.

  7. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

    Science.gov (United States)

    Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; Vasant, Drashtti; Brookes, Anthony J.; Zankl, Andreas; Washington, Nicole L.; Mungall, Christopher J.; Lewis, Suzanna E.; Haendel, Melissa A.; Parkinson, Helen; Robinson, Peter N.

    2015-01-01

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available. PMID:26119816

  8. Steroid synthesis by primary human keratinocytes; implications for skin disease

    Energy Technology Data Exchange (ETDEWEB)

    Hannen, Rosalind F., E-mail: r.f.hannen@qmul.ac.uk [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Michael, Anthony E. [Centre for Developmental and Endocrine Signalling, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, 3rd Floor, Lanesborough Wing, St. George' s, University of London, Cranmer Terrace, Tooting, London SW17 0RE (United Kingdom); Jaulim, Adil [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Bhogal, Ranjit [Life Science, Unilever R and D Colworth House, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Burrin, Jacky M. [Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ (United Kingdom); Philpott, Michael P. [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom)

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  9. Steroid synthesis by primary human keratinocytes; implications for skin disease

    International Nuclear Information System (INIS)

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-01

    Research highlights: → Primary keratinocytes express the steroid enzymes required for cortisol synthesis. → Normal primary human keratinocytes can synthesise cortisol. → Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. → StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3βHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7- 3 H]-pregnenolone through each steroid intermediate to [7- 3 H]-cortisol in cultured PHK. Trilostane (a 3βHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra

  10. The King James Bible and the Politics of Religious Education: Secular State and Sacred Scripture

    Science.gov (United States)

    Gearon, Liam

    2013-01-01

    This article provides an outline historical-educational analysis of the King James Bible from its 1611 publication through to its four-hundredth anniversary commemoration in 2011. With particular focus on England, the article traces the educational impact of the King James Bible and charts, in the country of its origin, its progressive decline in…

  11. Op zoek naar James Bond: media-pelgrimages, fans en masculiniteit

    NARCIS (Netherlands)

    Reijnders, S.

    2009-01-01

    Visiting the settings of popular films and tv series has become a growing niche in the tourist market. Little is known about what makes these visits so appealing. This question is explored on the basis of the case of James Bond. Twenty-three interviews were conducted with James Bond fans who had

  12. 78 FR 50458 - Entergy Nuclear Operations, Inc., James A. Fitzpatrick Nuclear Power Plant, Vermont Yankee...

    Science.gov (United States)

    2013-08-19

    ... Nuclear Operations, Inc., James A. Fitzpatrick Nuclear Power Plant, Vermont Yankee Nuclear Power Station... that the NRC take action with regard to James A. Fitzpatrick Nuclear Power Plant, Vermont Yankee.... Fitzpatrick Nuclear Power Plant (Fitzpatrick), Vermont Yankee Nuclear Power Station (Vermont Yankee), and...

  13. 75 FR 11575 - James A. Fitzpatrick Nuclear Power Plant Environmental Assessment and Finding of No Significant...

    Science.gov (United States)

    2010-03-11

    ... Power Plant Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear Regulatory...), for the operation of the James A. FitzPatrick Nuclear Power Plant (JAFNPP) located in Oswego County... the Final Environmental Statement for the James A. FitzPatrick Nuclear Power Plant, Docket No. 50-333...

  14. James Joyce kui religiooni subjekt ja objekt / Kalle Käsper

    Index Scriptorium Estoniae

    Käsper, Kalle, 1952-

    2003-01-01

    Arvustus: Joyce, James. Dublinlased : [novellid] / inglise keelest tõlkinud Jaak Rähesoo. 2. tr. [Tallinn] : Varrak, 2003 ; Joyce, James. Kunstniku noorpõlveportree : [romaan] / inglise keelest tõlkinud [ja järelsõna:] Jaak Rähesoo. [Tallinn] : Varrak, 2003; vt ka vastukaja: Raudam, Toomas. Kontra Käsper // Sirp (2003) 20. juuni, lk. 5

  15. 75 FR 49994 - James Stephen Ferguson, D.M.D.; Revocation of Registration

    Science.gov (United States)

    2010-08-16

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 09-64] James Stephen Ferguson, D.M.D.; Revocation of Registration On July 24, 2009, the Deputy Assistant Administrator, Office of Diversion Control, Drug Enforcement Administration (DEA), issued an Order to Show Cause to James Stephen...

  16. Pathogenesis of human papillomavirus-associated mucosal disease.

    Science.gov (United States)

    Groves, Ian J; Coleman, Nicholas

    2015-03-01

    Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  17. Bloomsday: James Joyce's Ulysses Celebrated as Theatrical Event

    Directory of Open Access Journals (Sweden)

    Willmar Sauter

    2009-12-01

    Full Text Available James Joyce had decided that 16 June 1904 should be the one day in the life of Leopold Bloom, about which he wrote his 800 page novel Ulysses. In his book, Joyce actually followed Mr Bloom that entire day, from his getting up and having the nowadays famous kidney breakfast, to the late evening, when he had to break into his own house on 7 Eccle Street to have a drink with Stephen Dedalus, the other main figure of the novel. The centenary of that very day took, accordingly, place in 2004. I have borrowed the identity of Mr Bloom to describe some street scenes from the centennial celebrations of Bloomsday in Dublin. After this intro-ductory presentation, part two of this article will attempt to analyse Bloomsday in terms of a Theatrical Event, embedded in an unusual and striking playing culture. In a third part, Mr Bloom will once more be allowed to make some concluding comments.

  18. Launch Window Trade Analysis for the James Webb Space Telescope

    Science.gov (United States)

    Yu, Wayne H.; Richon, Karen

    2014-01-01

    The James Webb Space Telescope (JWST) is a large-scale space telescope mission designed to study fundamental astrophysical questions ranging from the formation of the universe to the origin of planetary systems and the origins of life. JWSTs orbit design is a Libration Point Orbit (LPO) around the Sun-Earth/Moon (SEM) L2 point for a planned mission lifetime of 10.5 years. The launch readiness period for JWST is from Oct 1st, 2018 November 30th, 2018. This paper presents the first launch window analysis for the JWST observatory using finite-burn modeling; previous analysis assumed a single impulsive midcourse correction to achieve the mission orbit. The physical limitations of the JWST hardware stemming primarily from propulsion, communication and thermal requirements alongside updated mission design requirements result in significant launch window within the launch readiness period. Future plans are also discussed.

  19. Solar System Observations with the James Webb Space Telescope

    Science.gov (United States)

    Norwood, James; Hammel, Heidi; Milam, Stefanie; Stansberry, John; Lunine, Jonathan; Chanover, Nancy; Hines, Dean; Sonneborn, George; Tiscareno, Matthew; Brown, Michael; hide

    2016-01-01

    The James Webb Space Telescope (JWST) will enable a wealth of new scientific investigations in the near- and mid-infrared, with sensitivity and spatial/spectral resolution greatly surpassing its predecessors. In this paper, we focus upon Solar System science facilitated by JWST, discussing the most current information available concerning JWST instrument properties and observing techniques relevant to planetary science. We also present numerous example observing scenarios for a wide variety of Solar System targets to illustrate the potential of JWST science to the Solar System community. This paper updates and supersedes the Solar System white paper published by the JWST Project in 2010. It is based both on that paper and on a workshop held at the annual meeting of the Division for Planetary Sciences in Reno, NV, in 2012.

  20. The scientific papers of James Clerk Maxwell, vol.I

    CERN Document Server

    Maxwell, James Clerk

    2014-01-01

    One of the greatest theoretical physicists of the 19th century, James Clerk Maxwell is best known for his studies of the electromagnetic field. The 101 scientific papers of this two-volume set, arranged chronologically, testify to Maxwell's profound scientific legacy and include the preliminary explorations that culminated in his most famous work, A Treatise on Electricity and Magnetism. One of the nineteenth century's most significant papers, "A Dynamical Theory of the Electromagnetic Field," appears here, along with similarly influential expositions of Maxwell's dynamical theory of gases. The author's extensive range of interests is well represented, from his discussions of color blindness and the composition of Saturn's rings to his essays on geometrical optics, ether, and protecting buildings from lightning. His less technical writings are featured as well, including items written for the Encyclopedia Britannica and Nature magazine, book reviews, and popular lectures. Striking in their originality, these ...

  1. Astronaut James S. Voss Performs Tasks in the Destiny Laboratory

    Science.gov (United States)

    2001-01-01

    Astronaut James S. Voss, Expedition Two flight engineer, works with a series of cables on the EXPRESS Rack in the United State's Destiny laboratory on the International Space Station (ISS). The EXPRESS Rack is a standardized payload rack system that transports, stores, and supports experiments aboard the ISS. EXPRESS stands for EXpedite the PRocessing of Experiments to the Space Station, reflecting the fact that this system was developed specifically to maximize the Station's research capabilities. The EXPRESS Rack system supports science payloads in several disciplines, including biology, chemistry, physics, ecology, and medicine. With the EXPRESS Rack, getting experiments to space has never been easier or more affordable. With its standardized hardware interfaces and streamlined approach, the EXPRESS Rack enables quick, simple integration of multiple payloads aboard the ISS. The system is comprised of elements that remain on the ISS, as well as elements that travel back and forth between the ISS and Earth via the Space Shuttle.

  2. Swyer-James-Macleod's syndrome. A case report

    International Nuclear Information System (INIS)

    Pacheco C, Dario; Ojeda Leon, Paulina; Varo Acosta, Humberto; Salcedo Veles, Patricia; Salazar Juan Carlos

    1998-01-01

    This is a case report about a 67 years-old female patient with respiratory syndrome of 8 years with cough and dyspnoea. End-inspiration crackles in the pulmonary auscultation were found in left hemi thorax. Chest x-ray in expiration and inspiration showed hyperluscency and air trapping in the same hemi-thorax. Chest high-resolution CT revealed a low sized, oligohemic left lung with cylindrical bronchiectasis. Perfusion scintigraphy 99Tc labeled showed markedly left lung hypo-perfusion. Mild obstructive process was found in pulmonary function test. Lung biopsy of lingula reported bronchiolitis obliterans. Considered all the results that were obtained from clinical, x-ray and histopathology, a diagnosis of Swyer-James-Macleods syndrome was made

  3. Assimilating American Indians in James Fenimore Cooper’s Novels?

    Directory of Open Access Journals (Sweden)

    Peprník Michal

    2016-07-01

    Full Text Available The article employs critical concepts from sociology and anthropology to examine the stereotype of the Vanishing Indian and disclose its contradictory character. The article argues that in James Fenimore Cooper’s late novels from the 1840s a type of American Indian appears who can be regarded as a Vanishing Indian in many respects as he displays some slight degree of assimilation but at the same time he can be found to reveal a surprising amount of resistance to the process of vanishing and marginalization. His peculiar mode of survival and his mode of living demonstrate a certain degree of acculturation, which comes close to Gerald Vizenor’s survivance and for which I propose a term critical integration. I base my study on Susquesus (alias Trackless, Cooper’s less well-known character from The Littlepage Manuscripts, a three-book family saga.

  4. The case of James A. Garfield: a historical perspective.

    Science.gov (United States)

    Weiner, Bradley K

    2003-05-15

    In 1881, President James A. Garfield was shot in the back and died 79 days later. During this time, many controversies arose that had repercussions for years to come. Who was to manage the President's care? A prominent local physician took on the case, but after Garfield's death, he was highly criticized for inappropriate care and for excluding more highly qualified surgeons. Where was the bullet? Multiple opinions were given including that of Alexander Graham Bell. The correct suggestion turned out to be that of a young, unknown assistant demonstrator of anatomy. What was the proper treatment? Local wound care, removal of the bullet, and laparotomy all were considered. Many have felt that the choice of treatment may have proved to be worse than the injury itself. What did the autopsy show? Even this was controversial, with different observers claiming different results. This historical perspective reviews the case as well the controversies that surrounded it.

  5. Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.

    Science.gov (United States)

    Sanders, Angela; Hemmelgarn, Harmony; Melrose, Heather L; Hein, Leanne; Fuller, Maria; Clarke, Lorne A

    2013-08-01

    Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid β-glucosidase. The disease manifestations seen in Gaucher patients are highly heterogeneous as is the responsiveness to therapy. The elucidation of the precise factors responsible for this heterogeneity has been challenging as the development of clinically relevant animal models of Gaucher disease has been problematic. Although numerous murine models for Gaucher disease have been described each has limitations in their specific utility. We describe here, transgenic murine models of Gaucher disease that will be particularly useful for the study of pharmacological chaperones. We have produced stable transgenic mouse strains that individually express wild type, N370S and L444P containing human acid β-glucosidase and show that each of these transgenic lines rescues the lethal phenotype characteristic of acid β-glucosidase null mice. Both the N370S and L444P transgenic models show early and progressive elevations of tissue sphingolipids with L444P mice developing progressive splenic Gaucher cell infiltration. We demonstrate the potential utility of these new transgenic models for the study of Gaucher disease pathogenesis. In addition, since these mice produce only human enzyme, they are particularly relevant for the study of pharmacological chaperones that are specifically targeted to human acid β-glucosidase and the common mutations underlying Gaucher disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Dog as a model in studies on human hereditary diseases and their gene therapy.

    Science.gov (United States)

    Switonski, Marek

    2014-03-01

    During the last 15 years spectacular progress has been achieved in knowledge on the dog genome organization and the molecular background of hereditary diseases in this species. A majority of canine genetic diseases have their counterparts in humans and thus dogs are considered as a very important large animal model in human biomedicine. Among canine monogenic diseases with known causative gene mutations there are two large groups classified as retinal dystrophies and lysosomal storage diseases. Specific types of these diseases are usually diagnosed in a single or several breeds. A well known disorder, restricted to a single breed, is congenital stationary night blindness described in Briards. This disease is a counterpart of Leber amaurosis in children. On the other hand, one of the most common monogenic human diseases (Duchenne muscular dystrophy), has its canine counterparts in several breeds (e.g., the Golden retriever, Beagle and German short-haired pointer). For some of the canine diseases gene therapy strategy was successfully applied, e.g., for congenital stationary night blindness, rod-cone dystrophy and muccopolysaccharydoses type I, IIIB and VII. Since phenotypic variability between the breeds is exceptionally high, the dog is an interesting model to study the molecular background of congenital malformations (e.g., dwarfism and osteoporosis imperfecta). Also disorders of sexual development (DSD), especially testicular or ovotesticular DSD (78,XX; SRY-negative), which is widely distributed across dozens of breeds, are of particular interest. Studies on the genetic background of canine cancers, a major health problem in this species, are also quite advanced. On the other hand, genetic studies on canine counterparts of major human complex diseases (e.g., obesity, the metabolic syndrome and diabetes mellitus) are still in their infancy. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish

  7. [Dr James Lovelock and story about GAIA hypothesis].

    Science.gov (United States)

    Gajić, Vladimir

    2011-01-01

    Gaia is the Anglo-Saxon term for the Hellenic term Gea or Ge, which means Earth. The GAIA hypothesis was launched almost 40 years ago by the famous chemist James Lovelock, who was engaged by the National Aeronautics and Space Administration (NASA) to create a sensitive instrument for searching forms of extraterrestrial life on other planets. Then he published the book The ages of GAIA, which perturbed the world's scientific public of those days. Lovelock struck upon this idea in the late sixties of the past century, during the space race with Russians, when he was hired hy the National Aeronautics and Space Administration to conduct a series of experiments to find and explore life forms on the planet Mars. Experiments executed by the American module Viking failed to trace any life form, as Lovelock had predicted. He called it a dead equilibrium. Then he turned to Earth, whose perspective is totally different from its first neighbors. Venus and Mars, and is far from a dead equilibrium. DAISYWORLD: In this hypothesis. Lovelock represents Earth as one living, giant super organism, composed of all living creatures and its material environnent. In that super organisnm, the level of oxygen, weather conditions, ocean salinity and so on are under constant influence of physical, chemical and biological processes, which provide the existence for such life forms on Earth. Dr James Lovelock represents a pioneer of climatology, and his hypothesis gives a unique insight into the correlation of dynamic processes on our planet, no matter whether they are of physical or biological nature.

  8. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches.

    Science.gov (United States)

    Belizário, José E; Napolitano, Mauro

    2015-01-01

    The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body's microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.

  9. HUMAN MICROBIOMES AND THEIR ROLES IN DYSBIOSIS, COMMON DISEASES AND NOVEL THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    Jose Ernesto Belizario

    2015-10-01

    Full Text Available The human body is the residence of a large number of commensal (non-pathogenic and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics as well as phages engineered with CRISPR/cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community and common diseases (e.g. diabetes and obesity. The designing and production of pharmaceuticals based on our own body’s microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.

  10. Ethical issues in Alzheimer's disease research involving human subjects.

    Science.gov (United States)

    Davis, Dena S

    2017-12-01

    As we aggressively pursue research to cure and prevent Alzheimer's disease, we encounter important ethical challenges. None of these challenges, if handled thoughtfully, would pose insurmountable barriers to research. But if they are ignored, they could slow the research process, alienate potential study subjects and do damage to research recruits and others. These challenges are (1) the necessity of very large cohorts of research subjects, recruited for lengthy studies, probably ending only in the subjects' death; (2) the creation of cohorts of 'study ready' volunteers, many of whom will be competent to consent at the beginning of the process, but move into cognitive impairment later; (3) reliance on adaptive trial design, creating challenges for informed consent, equipoise and justice; (4) the use of biomarkers and predictive tests that describe risk rather than certainty, and that can threaten participants' welfare if the information is obtained by insurance companies or long-term care providers; (5) the use of study partners that creates unique risks of harm to the relationship of subject and study partner. We need greater attention, at all levels, to these complex ethical issues. Work on these issues should be included in research plans, from the federal to the local, and should be supported through NIH in the same way that it supported work on the ethical, legal and social implications of genetic research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Mineral density volume gradients in normal and diseased human tissues.

    Directory of Open Access Journals (Sweden)

    Sabra I Djomehri

    Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  12. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    Science.gov (United States)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  13. Automation Diagnosis of Skin Disease in Humans using Dempster-Shafer Method

    Science.gov (United States)

    Khairina, Dyna Marisa; Hatta, Heliza Rahmania; Rustam; Maharani, Septya

    2018-02-01

    Skin disease is an infectious disease that is common in people of all ages. Disorders of the skin often occur because there are factors, among others, are climate, environment, shelter, unhealthy living habits, allergies and others. Skin diseases in Indonesia are mostly caused by bacterial, fungal, parasitic, and allergies. The objective of the research is to diagnose skin diseases in humans by using the method of making decision tree then performing the search by forward chaining and calculating the probability value of Dempster-Shafer method. The results of research in the form of an automated system that can resemble an expert in diagnosing skin disease accurately and can help in overcoming the problem of skin diseases.

  14. Biodiversity loss, emerging infectious diseases and impact on human and crops

    International Nuclear Information System (INIS)

    Shinwari, Z.K.; Gilani, S.A.; Khan, A.L.

    2012-01-01

    We are losing biodiversity through several factors ranging from global warming, climatic change, unsustainable use of natural resources, human settlements, demand for food, medicine etc. Consequently, the biodiversity losses are causing emergence of infectious diseases (EIDs) which are making them more virulent than the past. Both biodiversity loss and emergence of diseases significantly impact the human derived benefits in-terms of economy and food. Ecological stability, productivity and food-web interactions are indirectly correlated with biodiversity and any change in these will cause losses in biodiversity that would certainly influence the human derived benefits and crops. The current article reviews the biodiversity losses and emerging infectious diseases at various levels reported by recent literature which will help in current status of EIDs and future recommendations. (author)

  15. Analysis of the genetic basis of disease in the context of worldwide human relationships and migration.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    2013-05-01

    Full Text Available Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.

  16. Perturbation of the Human Microbiome as a Contributor to Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Bayan Missaghi

    2014-06-01

    Full Text Available The human microbiome consist of the composite genome of native flora that have evolved with humanity over millennia and which contains 150-fold more genes than the human genome. A “healthy” microbiome plays an important role in the maintenance of health and prevention of illness, inclusive of autoimmune disease such as inflammatory bowel disease (IBD. IBD is a prevalent spectrum of disorders, most notably defined by Crohn’s disease (CD and ulcerative colitis (UC, which are associated with considerable suffering, morbidity, and cost. This review presents an outline of the loss of a normal microbiome as an etiology of immune dysregulation and IBD pathogenesis initiation. We, furthermore, summarize the knowledge on the role of a healthy microbiome in terms of its diversity and important functional elements and, lastly, conclude with some of the therapeutic interventions and modalities that are now being explored as potential applications of microbiome-host interactions.

  17. Circular RNAs: Biogenesis, Function and Role in Human Diseases

    Directory of Open Access Journals (Sweden)

    John Greene

    2017-06-01

    potential disease biomarkers and therapeutic targets in cancer.

  18. Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

    Science.gov (United States)

    Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

    2017-09-15

    Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

  19. Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases.

    Science.gov (United States)

    Lian, Qizhou; Chow, Yenyen; Esteban, Miguel Angel; Pei, Duanqing; Tse, Hung-Fat

    2010-07-01

    Recent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

  20. New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease.

    Science.gov (United States)

    Rühli, Frank Jakobus; Henneberg, Maciej

    2013-04-29

    Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations.

  1. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    Directory of Open Access Journals (Sweden)

    Daniel R. Bayzigitov

    2016-01-01

    Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

  2. Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans.

    Science.gov (United States)

    Li, Shan; Ganguli-Indra, Gitali; Indra, Arup K

    2016-05-01

    Lipidomics is the large-scale profiling and characterization of lipid species in a biological system using mass spectrometry. The skin barrier is mainly comprised of corneocytes and a lipid-enriched extracellular matrix. The major skin lipids are ceramides, cholesterol and free fatty acids (FFA). Lipid compositions are altered in inflammatory skin disorders with disrupted skin barrier such as atopic dermatitis (AD). Here we discuss some of the recent applications of lipidomics in human skin biology and in inflammatory skin diseases such as AD, psoriasis and Netherton syndrome. We also review applications of lipidomics in human skin equivalent and in pre-clinical animal models of skin diseases to gain insight into the pathogenesis of the skin disease. Expert commentary: Skin lipidomics analysis could be a fast, reliable and noninvasive tool to characterize the skin lipid profile and to monitor the progression of inflammatory skin diseases such as AD.

  3. Dissecting the role of AMP-activated protein kinase in human diseases

    Institute of Scientific and Technical Information of China (English)

    Jin Li; Liping Zhong; Fengzhong Wang; Haibo Zhu

    2017-01-01

    AMP-activated protein kinase (AMPK),known as a sensor and a master of cellular energy balance,integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of genetic methods and a plethora of AMPK agonists,rapid progress has identified AMPK as an attractive therapeutic target for several human diseases,such as cancer,type 2 diabetes,atherosclerosis,myocardial ischemia/reperfusion injury and neurodegenerative disease.The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere.In the present review,we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered.Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.

  4. Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology

    Directory of Open Access Journals (Sweden)

    Jessica M Hogestyn

    2018-01-01

    Full Text Available Human herpesviruses (HVs have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS. The ability of HVs to enter a state of latency, a defining characteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease (NDD pathology by highlighting two prominent members of the HV family, herpes simplex virus 1 (HSV-1 and human herpesvirus 6 (HHV-6. We (i introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then (ii review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer's disease (AD and multiple sclerosis (MS, respectively. We then (iii highlight and discuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we (iv discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.

  5. [Current situation of human resources of parasitic disease control and prevention organizations in Henan Province].

    Science.gov (United States)

    Ya-Lan, Zhang; Yan-Kun, Zhu; Wei-Qi, Chen; Yan, Deng; Peng, Li

    2018-01-10

    To understand the current status of human resources of parasitic disease control and prevention organizations in Henan Province, so as to provide the reference for promoting the integrative ability of the prevention and control of parasitic diseases in Henan Province. The questionnaires were designed and the method of census was adopted. The information, such as the amounts, majors, education background, technical titles, working years, and turnover in each parasitic disease control and prevention organization was collected by the centers for disease control and prevention (CDCs) at all levels. The data were descriptively analyzed. Totally 179 CDCs were investigated, in which only 19.0% (34/179) had the independent parasitic diseases control institution (department) . There were only 258 full-time staffs working on parasitic disease control and prevention in the whole province, in which only 61.9% (159/258) were health professionals. Those with junior college degree or below in the health professionals accounted for 60.3% (96/159) . Most of them (42.1%) had over 20 years of experience, but 57.9% (92/159) of their technical post titles were at primary level or below. The proportion of the health professionals is low in the parasitic disease control and prevention organizations in Henan Province. The human resource construction for parasitic disease control and prevention at all levels should be strengthened.

  6. Mice, humans and haplotypes--the hunt for disease genes in SLE.

    Science.gov (United States)

    Rigby, R J; Fernando, M M A; Vyse, T J

    2006-09-01

    Defining the polymorphisms that contribute to the development of complex genetic disease traits is a challenging, although increasingly tractable problem. Historically, the technical difficulties in conducting association studies across the entire human genome are such that murine models have been used to generate candidate genes for analysis in human complex diseases, such as SLE. In this article we discuss the advantages and disadvantages of this approach and specifically address some assumptions made in the transition from studying one species to another, using lupus as an example. These issues include differences in genetic structure and genetic organisation which are a reflection on the population history. Clearly there are major differences in the histories of the human population and inbred laboratory strains of mice. Both human and murine genomes do exhibit structure at the genetic level. That is to say, they comprise haplotypes which are genomic regions that carry runs of polymorphisms that are not independently inherited. Haplotypes therefore reduce the number of combinations of the polymorphisms in the DNA in that region and facilitate the identification of disease susceptibility genes in both mice and humans. There are now novel means of generating candidate genes in SLE using mutagenesis (with ENU) in mice and identifying mice that generate antinuclear autoimmunity. In addition, murine models still provide a valuable means of exploring the functional consequences of genetic variation. However, advances in technology are such that human geneticists can now screen large fractions of the human genome for disease associations using microchip technologies that provide information on upwards of 100,000 different polymorphisms. These approaches are aimed at identifying haplotypes that carry disease susceptibility mutations and rely less on the generation of candidate genes.

  7. Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

    Science.gov (United States)

    Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

    2014-01-01

    Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

  8. Noninvasive analysis of volatile biomarkers in human emanations for health and early disease diagnosis.

    Science.gov (United States)

    Kataoka, Hiroyuki; Saito, Keita; Kato, Hisato; Masuda, Kazufumi

    2013-06-01

    Early disease diagnosis is crucial for human healthcare and successful therapy. Since any changes in homeostatic balance can alter human emanations, the components of breath exhalations and skin emissions may be diagnostic biomarkers for various diseases and metabolic disorders. Since hundreds of endogenous and exogenous volatile organic compounds (VOCs) are released from the human body, analysis of these VOCs may be a noninvasive, painless, and easy diagnostic tool. Sampling and preconcentration by sorbent tubes/traps and solid-phase microextraction, in combination with GC or GC-MS, are usually used to analyze VOCs. In addition, GC-MS-olfactometry is useful for simultaneous analysis of odorants and odor quality. Direct MS techniques are also useful for the online real-time detection of VOCs. This review focuses on recent developments in sampling and analysis of volatile biomarkers in human odors and/or emanations, and discusses future use of VOC analysis.

  9. Haplotype association analysis of human disease traits using genotype data of unrelated individuals

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Christensen, Kaare

    2005-01-01

    unphased multi-locus genotype data, ranging from the early approach by the simple gene-counting method to the recent work using the generalized linear model. However, these methods are either confined to case – control design or unable to yield unbiased point and interval estimates of haplotype effects....... Based on the popular logistic regression model, we present a new approach for haplotype association analysis of human disease traits. Using haplotype-based parameterization, our model infers the effects of specific haplotypes (point estimation) and constructs confidence interval for the risks...... on the well-known logistic regression model is a useful tool for haplotype association analysis of human disease traits....

  10. Global and disease-associated genetic variation in the human Fanconi anemia gene family

    OpenAIRE

    Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

    2014-01-01

    Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population gen...

  11. Gamma-ray excision repair in normal and diseased human cells

    International Nuclear Information System (INIS)

    Cerutti, P.A.; Remsen, J.F.

    1976-01-01

    Radiation products of the 5,6-dihydroxy-dihydrothymine type (t') are efficiently removed from the DNA during postirradiation incubation of bacterial and mammalian cells. In this chapter we describe the t'-excision system contained in normal human cells, in human carcinoma HeLa S-3 cells, and in skin fibroblasts from xeroderma pigmentosum (XP) and Fanconi's anemia (FA) patients. The latter diseases are characterized among other symptoms by a genetically increased susceptibility for the development of cancer

  12. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    Energy Technology Data Exchange (ETDEWEB)

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  13. Genetic variation in lipid desaturases and its impact on the development of human disease.

    Science.gov (United States)

    Merino, Diana M; Ma, David W L; Mutch, David M

    2010-06-18

    Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.

  14. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    International Nuclear Information System (INIS)

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro

    2014-01-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

  15. Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases

    Directory of Open Access Journals (Sweden)

    Ivana Antonucci

    2016-04-01

    Full Text Available In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

  16. Human infectious disease burdens decrease with urbanization but not with biodiversity.

    Science.gov (United States)

    Wood, Chelsea L; McInturff, Alex; Young, Hillary S; Kim, DoHyung; Lafferty, Kevin D

    2017-06-05

    Infectious disease burdens vary from country to country and year to year due to ecological and economic drivers. Recently, Murray et al. (Murray CJ et al 2012 Lancet 380 , 2197-2223. (doi:10.1016/S0140-6736(12)61689-4)) estimated country-level morbidity and mortality associated with a variety of factors, including infectious diseases, for the years 1990 and 2010. Unlike other databases that report disease prevalence or count outbreaks per country, Murray et al. report health impacts in per-person disability-adjusted life years (DALYs), allowing comparison across diseases with lethal and sublethal health effects. We investigated the spatial and temporal relationships between DALYs lost to infectious disease and potential demographic, economic, environmental and biotic drivers, for the 60 intermediate-sized countries where data were available and comparable. Most drivers had unique associations with each disease. For example, temperature was positively associated with some diseases and negatively associated with others, perhaps due to differences in disease agent thermal optima, transmission modes and host species identities. Biodiverse countries tended to have high disease burdens, consistent with the expectation that high diversity of potential hosts should support high disease transmission. Contrary to the dilution effect hypothesis, increases in biodiversity over time were not correlated with improvements in human health, and increases in forestation over time were actually associated with increased disease burden. Urbanization and wealth were associated with lower burdens for many diseases, a pattern that could arise from increased access to sanitation and healthcare in cities and increased investment in healthcare. The importance of urbanization and wealth helps to explain why most infectious diseases have become less burdensome over the past three decades, and points to possible levers for further progress in improving global public health.This article is part

  17. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  18. Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Simone Thomas

    2015-07-01

    Full Text Available Reactivation of human cytomegalovirus (HCMV can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease.

  19. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

    Directory of Open Access Journals (Sweden)

    Matthew B Greenblatt

    Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

  20. Can the silkworm (Bombyx mori) be used as a human disease model?

    Science.gov (United States)

    Tabunoki, Hiroko; Bono, Hidemasa; Ito, Katsuhiko; Yokoyama, Takeshi

    2016-02-01

    Bombyx mori (silkworm) is the most famous lepidopteran in Japan. B. mori has long been used in the silk industry and also as a model insect for agricultural research. In recent years, B. mori has attracted interest in its potential for use in pathological analysis of model animals. For example, the human macular carotenoid transporter was discovered using information of B. mori carotenoid transporter derived from yellow-cocoon strain. The B. mori carotenoid transport system is useful in human studies. To develop a human disease model, we characterized the human homologs of B. mori, and by constructing KAIKO functional annotation pipeline, and to analyze gene expression profile of a unique B. mori mutant strain using microarray analysis. As a result, we identified a novel molecular network involved in Parkinson's disease. Here we describe the potential use of a spontaneous mutant silkworm strain as a human disease model. We also summarize recent progress in the application of genomic information for annotation of human homologs in B. mori. The B. mori mutant will provide a clue to pathological mechanisms, and the findings will be helpful for the development of therapies and for medical drug discovery.

  1. Prioritizing Zoonotic Diseases: Differences in Perspectives Between Human and Animal Health Professionals in North America.

    Science.gov (United States)

    Ng, V; Sargeant, J M

    2016-05-01

    Zoonoses pose a significant burden of illness in North America. Zoonoses represent an additional threat to public health because the natural reservoirs are often animals, particularly wildlife, thus eluding control efforts such as quarantine, vaccination and social distancing. As there are limited resources available, it is necessary to prioritize diseases in order to allocate resources to those posing the greatest public health threat. Many studies have attempted to prioritize zoonoses, but challenges exist. This study uses a quantitative approach, conjoint analysis (CA), to overcome some limitations of traditional disease prioritization exercises. We used CA to conduct a zoonoses prioritization study involving a range of human and animal health professionals across North America; these included epidemiologists, public health practitioners, research scientists, physicians, veterinarians, laboratory technicians and nurses. A total of 699 human health professionals (HHP) and 585 animal health professionals (AHP) participated in this study. We used CA to prioritize 62 zoonotic diseases using 21 criteria. Our findings suggest CA can be used to produce reasonable criteria scores for disease prioritization. The fitted models were satisfactory for both groups with a slightly better fit for AHP compared to HHP (84.4% certainty fit versus 83.6%). Human-related criteria were more influential for HHP in their decision to prioritize zoonoses, while animal-related criteria were more influential for AHP resulting in different disease priority lists. While the differences were not statistically significant, a difference of one or two ranks could be considered important for some individuals. A potential solution to address the varying opinions is discussed. The scientific framework for disease prioritization presented can be revised on a regular basis by updating disease criteria to reflect diseases as they evolve over time; such a framework is of value allowing diseases of

  2. Prevalence of Hookworm infection and Strongyloidiasis in Cats and Potential Risk Factor of Human Diseases

    Science.gov (United States)

    Sedionoto, Blego; Anamnart, Witthaya

    2018-02-01

    Hookworm infection and Stronyloidiasis are public health problem in the worldwide which both of them could infective in human by penetrated on skin and they have potential risk from Gastrointestinal zoonotic helminths of pets, including cats. We investigated the prevalence soil transmitted helminths infection in human and cats used modified Formal-Ether Concentration and agar plate culture. Fecal samples of 23 cats and human from Naitung and Subua Villages (area study 1), and fecal samples of 15 cats and 17 humans from Thasala Beach villages (area study 2) were collected. Result of study in area study 1 showed prevalence of infection in human was not hookworm and strongyloidiasis but 10% humans have infected Ascaris and Tricuris, and in cats have infected by hookworm 75.2% and S. strercoralis 8.5%, toxocara 13%, spirometra 13% and overall prevalence 82.5%. In area study 2 showed in human has infected by Trichuris 100% and S. stercoralis 29.4% and in cats have infected by hookworm 100% and S. strercoralis 40%, toxocora 20%, and spirometra 20%. Helminth infection found in both humans in two areas study are S. strercoralis. Hookworms were the most common helminth in cats but did not connection with infection in human, while S. strercoralis was helminth infection in cats which has potential zoonotic disease to human.

  3. [SWOT Analysis of the National Survey on Current Status of Major Human Parasitic Diseases in China].

    Science.gov (United States)

    ZHU, Hui-hui; ZHOU, Chang-hai; CHEN, Ying-dan; ZANG, Wei; XIAO, Ning; ZHOU, Xiao-nong

    2015-10-01

    The National Survey on Current Status of Major Human Parasitic Diseases in China has been carried out since 2014 under the organization of the National Health and Family Planning Commission of the People's Republic of China. The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (NIPD, China CDC) provided technical support and was responsible for quality control in this survey. This study used SWOT method to analyze the strengths, weaknesses, opportunities and threats that were encountered by he NIPD, China CDC during the completion of the survey. Accordingly, working strategies were proposed to facilitate the future field work.

  4. A New Face of Cardiac Emergencies: Human Immunodeficiency Virus-Related Cardiac Disease.

    Science.gov (United States)

    Tsabedze, Nqoba; Vachiat, Ahmed; Zachariah, Don; Manga, Pravin

    2018-02-01

    The human immunodeficiency virus epidemic is a major health challenge of the twenty-first century as the transition from infectious complications to noncommunicable disease becomes more evident. These patients may present to the emergency department with a variety of cardiovascular diseases, such as acute coronary syndromes, heart failure, pericardial disease, infective endocarditis, venothromboembolism, and other conditions. Increased awareness is needed among health care professionals to enhance adequate identification and promote prompt management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Metagenomic analysis of planktonic microbial consortia from a non-tidal urban-impacted segment of James River.

    Science.gov (United States)

    Brown, Bonnie L; LePrell, Rebecca V; Franklin, Rima B; Rivera, Maria C; Cabral, Francine M; Eaves, Hugh L; Gardiakos, Vicki; Keegan, Kevin P; King, Timothy L

    2015-01-01

    effects, and revealed the noteworthy presence of 22 human-pathogenic bacterial genera (e.g., Enterobacteriaceae, pathogenic Pseudomonadaceae, and 'Vibrionales') and 6 pathogenic eukaryotic genera (e.g., Trypanosomatidae and Vahlkampfiidae). This information about pathogen diversity may be used to promote human epidemiological studies, enhance existing water quality monitoring efforts, and increase awareness of the possible health risks associated with recreational use of James River.

  6. PHD fingers in human diseases: Disorders arising from misinterpreting epigenetic marks

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Lindsey A. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States); Allis, C. David [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: alliscd@rockefeller.edu; Wang, Gang G. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: gwang@rockefeller.edu

    2008-12-01

    Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved 'reader/effector' modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized 'reader' modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., 'writers' and 'erasers') are already known to be involved in various human diseases, mutations in the modification-specific 'reader' proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies

  7. PHD fingers in human diseases: Disorders arising from misinterpreting epigenetic marks

    International Nuclear Information System (INIS)

    Baker, Lindsey A.; Allis, C. David; Wang, Gang G.

    2008-01-01

    Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved 'reader/effector' modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized 'reader' modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., 'writers' and 'erasers') are already known to be involved in various human diseases, mutations in the modification-specific 'reader' proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies wherein 'chromatin readers' stand as potential drug

  8. Linking human diseases to animal models using ontology-based phenotype annotation.

    Directory of Open Access Journals (Sweden)

    Nicole L Washington

    2009-11-01

    Full Text Available Scientists and clinicians who study genetic alterations and disease have traditionally described phenotypes in natural language. The considerable variation in these free-text descriptions has posed a hindrance to the important task of identifying candidate genes and models for human diseases and indicates the need for a computationally tractable method to mine data resources for mutant phenotypes. In this study, we tested the hypothesis that ontological annotation of disease phenotypes will facilitate the discovery of new genotype-phenotype relationships within and across species. To describe phenotypes using ontologies, we used an Entity-Quality (EQ methodology, wherein the affected entity (E and how it is affected (Q are recorded using terms from a variety of ontologies. Using this EQ method, we annotated the phenotypes of 11 gene-linked human diseases described in Online Mendelian Inheritance in Man (OMIM. These human annotations were loaded into our Ontology-Based Database (OBD along with other ontology-based phenotype descriptions of mutants from various model organism databases. Phenotypes recorded with this EQ method can be computationally compared based on the hierarchy of terms in the ontologies and the frequency of annotation. We utilized four similarity metrics to compare phenotypes and developed an ontology of homologous and analogous anatomical structures to compare phenotypes between species. Using these tools, we demonstrate that we can identify, through the similarity of the recorded phenotypes, other alleles of the same gene, other members of a signaling pathway, and orthologous genes and pathway members across species. We conclude that EQ-based annotation of phenotypes, in conjunction with a cross-species ontology, and a variety of similarity metrics can identify biologically meaningful similarities between genes by comparing phenotypes alone. This annotation and search method provides a novel and efficient means to identify

  9. 75 FR 59237 - TRICARE Co-Pay Waiver at Captain James A. Lovell Federal Health Care Center Demonstration Project

    Science.gov (United States)

    2010-09-27

    ... DEPARTMENT OF DEFENSE Office of the Secretary TRICARE Co-Pay Waiver at Captain James A. Lovell.... ACTION: Notice of TRICARE Co-Pay waiver at Captain James A. Lovell Federal Health Care Center... ``TRICARE Co-Pay Waiver at Captain James A. Lovell Federal Health Care (FHCC) Demonstration Project.'' Under...

  10. The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases.

    Science.gov (United States)

    Brodziak, Andrzej; Ziółko, Ewa; Muc-Wierzgoń, Małgorzata; Nowakowska-Zajdel, Ewa; Kokot, Teresa; Klakla, Katarzyna

    2012-06-01

    This paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants "vertically" by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.

  11. Computational study of ‘HUB’ microRNA in human cardiac diseases

    Science.gov (United States)

    Krishnan, Remya; Nair, Achuthsankar S.; Dhar, Pawan K.

    2017-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs ~22 nucleotides long that do not encode for proteins but have been reported to influence gene expression in normal and abnormal health conditions. Though a large body of scientific literature on miRNAs exists, their network level profile linking molecules with their corresponding phenotypes, is less explored. Here, we studied a network of 191 human miRNAs reported to play a role in 30 human cardiac diseases. Our aim was to study miRNA network properties like hubness and preferred associations, using data mining, network graph theory and statistical analysis. A total of 16 miRNAs were found to have a disease node connectivity of >5 edges (i.e., they were linked to more than 5 diseases) and were considered hubs in the miRNAcardiac disease network. Alternatively, when diseases were considered as hubs, >10 of miRNAs showed up on each ‘disease hub node’. Of all the miRNAs associated with diseases, 19 miRNAs (19/24= 79.1% of upregulated events) were found to be upregulated in atherosclerosis. The data suggest micro RNAs as early stage biological markers in cardiac conditions with potential towards microRNA based therapeutics. PMID:28479745

  12. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    Directory of Open Access Journals (Sweden)

    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  13. Global burden of human brucellosis: a systematic review of disease frequency.

    Directory of Open Access Journals (Sweden)

    Anna S Dean

    Full Text Available BACKGROUND: This report presents a systematic review of scientific literature published between 1990-2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY estimate for brucellosis. METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden. CONCLUSIONS: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a

  14. A knowledge based approach to matching human neurodegenerative disease and animal models

    Directory of Open Access Journals (Sweden)

    Maryann E Martone

    2013-05-01

    Full Text Available Neurodegenerative diseases present a wide and complex range of biological and clinical features. Animal models are key to translational research, yet typically only exhibit a subset of disease features rather than being precise replicas of the disease. Consequently, connecting animal to human conditions using direct data-mining strategies has proven challenging, particularly for diseases of the nervous system, with its complicated anatomy and physiology. To address this challenge we have explored the use of ontologies to create formal descriptions of structural phenotypes across scales that are machine processable and amenable to logical inference. As proof of concept, we built a Neurodegenerative Disease Phenotype Ontology and an associated Phenotype Knowledge Base using an entity-quality model that incorporates descriptions for both human disease phenotypes and those of animal models. Entities are drawn from community ontologies made available through the Neuroscience Information Framework and qualities are drawn from the Phenotype and Trait Ontology. We generated ~1200 structured phenotype statements describing structural alterations at the subcellular, cellular and gross anatomical levels observed in 11 human neurodegenerative conditions and associated animal models. PhenoSim, an open source tool for comparing phenotypes, was used to issue a series of competency questions to compare individual phenotypes among organisms and to determine which animal models recapitulate phenotypic aspects of the human disease in aggregate. Overall, the system was able to use relationships within the ontology to bridge phenotypes across scales, returning non-trivial matches based on common subsumers that were meaningful to a neuroscientist with an advanced knowledge of neuroanatomy. The system can be used both to compare individual phenotypes and also phenotypes in aggregate. This proof of concept suggests that expressing complex phenotypes using formal

  15. High Leptospira Diversity in Animals and Humans Complicates the Search for Common Reservoirs of Human Disease in Rural Ecuador.

    Science.gov (United States)

    Barragan, Veronica; Chiriboga, Jorge; Miller, Erin; Olivas, Sonora; Birdsell, Dawn; Hepp, Crystal; Hornstra, Heidie; Schupp, James M; Morales, Melba; Gonzalez, Manuel; Reyes, Soraya; de la Cruz, Carmen; Keim, Paul; Hartskeerl, Rudy; Trueba, Gabriel; Pearson, Talima

    2016-09-01

    Leptospirosis is a zoonotic disease responsible for high morbidity around the world, especially in tropical and low income countries. Rats are thought to be the main vector of human leptospirosis in urban settings. However, differences between urban and low-income rural communities provide additional insights into the epidemiology of the disease. Our study was conducted in two low-income rural communities near the coast of Ecuador. We detected and characterized infectious leptospira DNA in a wide variety of samples using new real time quantitative PCR assays and amplicon sequencing. We detected infectious leptospira in a high percentage of febrile patients (14.7%). In contrast to previous studies on leptospirosis risk factors, higher positivity was not found in rats (3.0%) but rather in cows (35.8%) and pigs (21.1%). Six leptospira species were identified (L. borgpetersenii, L kirschnerii, L santarosai, L. interrogans, L noguchii, and an intermediate species within the L. licerasiae and L. wolffii clade) and no significant differences in the species of leptospira present in each animal species was detected (χ2 = 9.89, adj.p-value = 0.27). A large portion of the world's human population lives in low-income, rural communities, however, there is limited information about leptospirosis transmission dynamics in these settings. In these areas, exposure to peridomestic livestock is particularly common and high prevalence of infectious leptospira in cows and pigs suggest that they may be the most important reservoir for human transmission. Genotyping clinical samples show that multiple species of leptospira are involved in human disease. As these genotypes were also detected in samples from a variety of animals, genotype data must be used in conjunction with epidemiological data to provide evidence of transmission and the importance of different potential leptospirosis reservoirs.

  16. Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Nicola Gaetano Gatta

    2016-11-01

    Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or –OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review describes the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

  17. Zoonotic Infections in Communities of the James Bay Cree Territory: An Overview of Seroprevalence

    Directory of Open Access Journals (Sweden)

    Hugues Sampasa-Kanyinga

    2013-01-01

    Full Text Available The Cree communities of James Bay are at risk for contracting infectious diseases transmitted by wildlife. Data from serological testing for a range of zoonotic infections performed in the general population (six communities, or trappers and their spouses (one community, were abstracted from four population-based studies conducted in Cree territory (Quebec between 2005 and 2009. Evidence of exposure to Trichinella species, Toxoplasma gondii, Toxocara canis, Echinococcus granulosus, Leptospira species, Coxiella burnetii and Francisella tularensis was verified in all communities, whereas antibodies against Sin Nombre virus and California serogroup viruses (Jamestown Canyon and snowshoe hare viruses were evaluated in three and six communities, respectively. Seroprevalence varied widely among communities: snowshoe hare virus (1% to 42%, F tularensis (14% to 37%, Leptospira species (10% to 27%, Jamestown Canyon virus (9% to 24%, C burnetii (0% to 18%, T gondii (4% to 12%, T canis (0% to 10%, E granulosus (0% to 4% and Trichinella species (0% to 1%. No subject had serological evidence of Sin Nombre virus exposure. These data suggest that large proportions of the Cree population have been exposed to at least one of the targeted zoonotic agents. The Cree population, particularly those most heavily exposed to fauna, as well as the medical staff living in these regions, should be aware of these diseases. Greater awareness would not only help to decrease exposures but would also increase the chance of appropriate diagnostic testing.

  18. Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies

    Science.gov (United States)

    Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.

    2011-01-01

    Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

  19. Analysis of indel variations in the human disease-associated genes ...

    Indian Academy of Sciences (India)

    Keywords. insertion–deletion variations; haematological disease; tumours; human genetics. Journal of Genetics ... domly selected healthy Korean individuals using a blood genomic DNA ... Bioinformatics annotation and 3-D protein structure analysis. In this study ..... 2009 A genome-wide meta-analysis identifies. Journal of ...

  20. The Expression of DJ-1 (PARK7) in Normal Human CNS and Idiopathic Parkinson's Disease

    Science.gov (United States)

    Bandopadhyay, Rina; Kingsbury, Ann E.; Cookson, Mark R.; Reid, Andrew R.; Evans, Ian M.; Hope, Andrew D.; Pittman, Alan M.; Lashley, Tammaryn; Canet-Aviles, Rosa; Miller, David W.; McLendon, Chris; Strand, Catherine; Leonard, Andrew J.; Abou-Sleiman, Patrick M.; Healy, Daniel G.; Ariga, Hiroyashi; Wood, Nicholas W.; de Silva, Rohan; Revesz, Tamas; Hardy, John A.; Lees, Andrew J.

    2004-01-01

    Two mutations in the DJ-1 gene on chromosome1p36 have been identified recently to cause early-onset, autosomal recessive Parkinson's disease. As no information is available regarding the distribution of DJ-1 protein in the human brain, in this study we used a monoclonal antibody for DJ-1 to map its distribution in frontal cortex and substantia…

  1. Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

    NARCIS (Netherlands)

    E.A. Croes (Esther); F. Forey; G.H. Jansen; P.C. Nijssen; C.M. van Duijn (Cornelia)

    2002-01-01

    textabstractA 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic

  2. Bacteria, Yeast, Worms, and Flies: Exploiting Simple Model Organisms to Investigate Human Mitochondrial Diseases

    Science.gov (United States)

    Rea, Shane L.; Graham, Brett H.; Nakamaru-Ogiso, Eiko; Kar, Adwitiya; Falk, Marni J.

    2010-01-01

    The extensive conservation of mitochondrial structure, composition, and function across evolution offers a unique opportunity to expand our understanding of human mitochondrial biology and disease. By investigating the biology of much simpler model organisms, it is often possible to answer questions that are unreachable at the clinical level.…

  3. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    DEFF Research Database (Denmark)

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single ...

  4. Human Induced Pluripotent stem cells and their derivatives for disease modeling and therapeutic applications in Alzheimer's disease

    DEFF Research Database (Denmark)

    Pires, C.; Hall, V.; Freude, K. K.

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) have recently been generated for various inherited diseases. These hiPSC have the capacity to differentiate into any given cell type withthe help of small compounds and growth factors aiding the process. In Alzheimer’s disease (AD) several specific...... neural subpopulations in the brain are more susceptible to degeneration and apoptosis and hiPSCs can be used in order to generate these subpopulations in cell culture dishes via directed differentiation. Subsequently these cells can be used to optimize small compound screens to identify novel drug......, followed by a description of the methods used to generate isogenic controls. We will also discuss the possibilities and limitations of current neural differentiation protocols for AD to obtain relevant neuronal subtypes. In the end we will elaborate on the possibilities and current issues of hiPSC for cell...

  5. New variant of Creutzfeldt-Jakob (vCJD disease and other human prion diseases under epidemiological surveillance in Brazil

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Gattás

    Full Text Available Abstract To increase the timeliness of detection of human cases of the new variant of Creutzfeldt-Jakob disease (vCJD and to reduce the risk of transmission, the Brazilian Ministry of Health has established and standardized rules and control measures. These include the definition of criteria for suspect cases, reporting, monitoring, and control measures for illness prevention and transmission. Guidelines to be used by the team of health care staff were published and distributed to health workers. A detailed proposal for a simplified system of surveillance for prion diseases was developed and mandatory reporting introduced. Additional effort is necessary to increase vCJD case detection, thus making it necessary to establish a partnership with health care services for best identification of suspected cases and dissemination of information to all involved in the service dealing with vCJD investigation.

  6. Estimating the global burden of thalassogenic diseases: human infectious diseases caused by wastewater pollution of the marine environment.

    Science.gov (United States)

    Shuval, Hillel

    2003-06-01

    This paper presents a preliminary attempt at obtaining an order-of-magnitude estimate of the global burden of disease (GBD) of human infectious diseases associated with swimming/bathing in coastal waters polluted by wastewater, and eating raw or lightly steamed filter-feeding shellfish harvested from such waters. Such diseases will be termed thalassogenic--caused by the sea. Until recently these human health effects have been viewed primarily as local phenomena, not generally included in the world agenda of marine scientists dealing with global marine pollution problems. The massive global scale of the problem can be visualized when one considers that the wastewater and human body wastes of a significant portion of the world's population who reside along the coastline or in the vicinity of the sea are discharged daily, directly or indirectly, into the marine coastal waters, much of it with little or no treatment. Every cubic metre of raw domestic wastewater discharged into the sea can carry millions of infectious doses of pathogenic microorganisms. It is estimated that globally, foreign and local tourists together spend some 2 billion man-days annually at coastal recreational resorts and many are often exposed there to coastal waters polluted by wastewater. Annually some 800 million meals of potentially contaminated filter-feeding shellfish/bivalves and other sea foods, harvested in polluted waters are consumed, much of it raw or lightly steamed. A number of scientific studies have shown that swimmers swallow significant amounts of polluted seawater and can become ill with gastrointestinal and respiratory diseases from the pathogens they ingest. Based on risk assessments from the World Health Organization (WHO) and academic research sources the present study has made an estimate that globally, each year, there are in excess of 120 million cases of gastrointestinal disease and in excess of 50 million cases of more severe respiratory diseases caused by swimming and

  7. Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

    Science.gov (United States)

    Bakker, Barbara M; van Eunen, Karen; Jeneson, Jeroen A L; van Riel, Natal A W; Bruggeman, Frank J; Teusink, Bas

    2010-10-01

    Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

  8. The emerging paradigm of network medicine in the study of human disease.

    Science.gov (United States)

    Chan, Stephen Y; Loscalzo, Joseph

    2012-07-20

    The molecular pathways that govern human disease consist of molecular circuits that coalesce into complex, overlapping networks. These network pathways are presumably regulated in a coordinated fashion, but such regulation has been difficult to decipher using only reductionistic principles. The emerging paradigm of "network medicine" proposes to utilize insights garnered from network topology (eg, the static position of molecules in relation to their neighbors) as well as network dynamics (eg, the unique flux of information through the network) to understand better the pathogenic behavior of complex molecular interconnections that traditional methods fail to recognize. As methodologies evolve, network medicine has the potential to capture the molecular complexity of human disease while offering computational methods to discern how such complexity controls disease manifestations, prognosis, and therapy. This review introduces the fundamental concepts of network medicine and explores the feasibility and potential impact of network-based methods for predicting individual manifestations of human disease and designing rational therapies. Wherever possible, we emphasize the application of these principles to cardiovascular disease.

  9. CCR8 signaling influences Toll-like receptor 4 responses in human macrophages in inflammatory diseases.

    Science.gov (United States)

    Reimer, Martina Kvist; Brange, Charlotte; Rosendahl, Alexander

    2011-12-01

    CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients.

  10. Non-communicable diseases and human rights: Global synergies, gaps and opportunities.

    Science.gov (United States)

    Ferguson, Laura; Tarantola, Daniel; Hoffmann, Michael; Gruskin, Sofia

    2017-10-01

    The incorporation of human rights in health policy and programmes is known to strengthen responses to health problems and help address disparities created or exacerbated by illness yet this remains underexplored in relation to non-communicable diseases (NCDs). Aiming to understand existing synergies and how they might be further strengthened, we assessed the extent to which human rights are considered in global NCD policies and strategies and the degree of attention given to NCDs by select United Nations human rights mechanisms. Across global NCD policies and strategies, rhetorical assertions regarding human rights appear more often than actionable statements, thus limiting their implementation and impact. Although no human rights treaty explicitly mentions NCDs, some human rights monitoring mechanisms have been paying increasing attention to NCDs. This provides important avenues for promoting the incorporation of human rights norms and standards into NCD responses as well as for accountability. Linking NCDs and human rights at the global level is critical for encouraging national-level action to promote better outcomes relating to both health and human rights. The post-2015 development agenda constitutes a key entry point for highlighting these synergies and strengthening opportunities for health and rights action at global, national and local levels.

  11. Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies

    Directory of Open Access Journals (Sweden)

    Karina O. Brandão

    2017-09-01

    Full Text Available It is now a decade since human induced pluripotent stem cells (hiPSCs were first described. The reprogramming of adult somatic cells to a pluripotent state has become a robust technology that has revolutionised our ability to study human diseases. Crucially, these cells capture all the genetic aspects of the patient from which they were derived. Combined with advances in generating the different cell types present in the human heart, this has opened up new avenues to study cardiac disease in humans and investigate novel therapeutic approaches to treat these pathologies. Here, we provide an overview of the current state of the field regarding the generation of cardiomyocytes from human pluripotent stem cells and methods to assess them functionally, an essential requirement when investigating disease and therapeutic outcomes. We critically evaluate whether treatments suggested by these in vitro models could be translated to clinical practice. Finally, we consider current shortcomings of these models and propose methods by which they could be further improved.

  12. Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis.

    Science.gov (United States)

    van 't Erve, Thomas J; Kadiiska, Maria B; London, Stephanie J; Mason, Ronald P

    2017-08-01

    The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures. In this meta-analysis, the F 2 -isoprostane, 8-iso-PGF 2α , was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges' g) in 8-iso-PGF 2α levels between affected and control populations were calculated. The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF 2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF 2α levels (ganalysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation. Copyright © 2017. Published by Elsevier B.V.

  13. Monkey-based research on human disease: the implications of genetic differences.

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.

  14. Decrease in Hurst exponent of human gait with aging and neurodegenerative diseases

    International Nuclear Information System (INIS)

    Zhauang Jianjun; Ning Xinbao; Yang Xiaodong; Huo Chengyu; Hou Fengzhen

    2008-01-01

    In this paper the decrease in the Hurst exponent of human gait with aging and neurodegenerative diseases was observed by using an improved rescaled range (R/S) analysis method. It indicates that the long-range correlations of gait rhythm from young healthy people are stronger than those from the healthy elderly and the diseased. The result further implies that fractal dynamics in human gait will be altered due to weakening or impairment of neural control on locomotion resulting from aging and neurodegenerative diseases. Due to analysing short-term data sequences rather than long datasets required by most nonlinear methods, the algorithm has the characteristics of simplicity and sensitivity, most importantly, fast calculation as well as powerful anti-noise capacities. These findings have implications for modelling locomotor control and also for quantifying gait dynamics in varying physiologic and pathologic states

  15. Receptors for sensory neuropeptides in human inflammatory diseases: Implications for the effector role of sensory neurons

    International Nuclear Information System (INIS)

    Mantyh, P.W.; Catton, M.D.; Boehmer, C.G.; Welton, M.L.; Passaro, E.P. Jr.; Maggio, J.E.; Vigna, S.R.

    1989-01-01

    Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues

  16. Mitochondrial Damage-Associated Molecular Patterns: From Inflammatory Signaling to Human Diseases

    Directory of Open Access Journals (Sweden)

    Serge Grazioli

    2018-05-01

    Full Text Available Over the recent years, much has been unraveled about the pro-inflammatory properties of various mitochondrial molecules once they are leaving the mitochondrial compartment. On entering the cytoplasm or the extracellular space, mitochondrial DAMPs (also known as mitochondrial alarmins can become pro-inflammatory and initiate innate and adaptive immune responses by activating cell surface and intracellular receptors. Current evidence indicates that uncontrolled and excessive release of mitochondrial DAMPs is associated with severity, has prognosis value in human diseases, and contributes to the dysregulated process observed in numerous inflammatory and autoimmune conditions, as well as in ischemic heart disease and cancer. Herein, we review that the expanding research field of mitochondrial DAMPs in innate immune responses and the current knowledge on the association between mitochondrial DAMPs and human diseases.

  17. Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Wadsworth, Jonathan D F; Joiner, Susan; Linehan, Jacqueline M; Balkema-Buschmann, Anne; Spiropoulos, John; Simmons, Marion M; Griffiths, Peter C; Groschup, Martin H; Hope, James; Brandner, Sebastian; Asante, Emmanuel A; Collinge, John

    2013-11-01

    Public and animal health controls to limit human exposure to animal prions are focused on bovine spongiform encephalopathy (BSE), but other prion strains in ruminants may also have zoonotic potential. One example is atypical/Nor98 scrapie, which evaded statutory diagnostic methods worldwide until the early 2000s. To investigate whether sheep infected with scrapie prions could be another source of infection, we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of classical and atypical scrapie, sheep with experimental BSE, and cattle with BSE. We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods when mice were inoculated with classical or atypical scrapie prions. These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to naturally occurring prions of sheep than after exposure to epizootic BSE prions of ruminants.

  18. Cracking the Code of Human Diseases Using Next-Generation Sequencing: Applications, Challenges, and Perspectives

    Directory of Open Access Journals (Sweden)

    Vincenza Precone

    2015-01-01

    Full Text Available Next-generation sequencing (NGS technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing. These features, together with the technology’s flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases. Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation. These approaches are now widely used in research, and they are already being used in routine molecular diagnostics. However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects. Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics.

  19. Possible pathophysiological roles of transglutaminase-catalyzed reactions in the pathogenesis of human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Enrica Serretiello

    2015-09-01

    Full Text Available Transglutaminases (TG, E.C. 2.3.2.13 are related and ubiquitous enzymes that catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other post-translational reactions important for cell life. The distribution and the physiological roles of human TGs have been widely studied in numerous cell types and tissues and recently their roles in several diseases have begun to be identified. It has been hypothesized that transglutaminase activity is directly involved in the pathogenetic mechanisms responsible for several human diseases. In particular, tissue TG (tTG, TG2, a member of the TG enzyme family, has been recently shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD, one of the most common food intolerances described in the western population. The main food agent that provokes the strong and diffuse clinical symptoms has been known for several years to be gliadin, a protein present in a very large number of human foods derived from vegetables. Recently, some biochemical and immunological aspects of this very common disease have been clarified, and “tissue” transglutaminase, a multifunctional and ubiquitous enzyme, has been identified as one of the major factors. The aim of this review is to summarize the most recent findings concerning the relationships between the biochemical properties of the transglutaminase activity and the basic molecular mechanisms responsible for some human diseases, with particular reference to neuropsychiatric disorders. Possible molecular links between CD and neuropsychiatric disorders, and the use of transglutaminase inhibitors are also discussed.

  20. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

    Directory of Open Access Journals (Sweden)

    Kathryn Patterson Sutherland

    Full Text Available Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS, a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens to a marine invertebrate (A. palmata. These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.