Will vaccination against human papillomavirus prevent eye disease? A review of the evidence.

PubMed

Hughes, D S; Powell, N; Fiander, A N

2008-04-01

The role of human papillomavirus (HPV) infection in eye disease is controversial. However, a recent case illustrates the possible role of HPV in conjunctival squamous carcinoma and the potentially devastating effects of this disease. The development of two vaccines to prevent infection with HPV types most commonly associated with anogenital cancers has led to debate about the pros and cons of a national immunisation programme to prevent cervical cancer. The introduction of such a vaccination programme may have an additional beneficial effect on the occurrence of some head and neck, including ocular, cancers. This review discusses the nature of papillomaviruses, mechanisms of infection and carcinogenesis, the possible role of HPV in eye disease, and finally the likely impact of the new prophylactic vaccines.

Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

PubMed Central

Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

2012-01-01

Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

Fungal disease and the developing story of bat white-nose syndrome

USGS Publications Warehouse

Blehert, David S.

2012-01-01

Two recently emerged cutaneous fungal diseases of wildlife, bat white-nose syndrome (WNS) and amphibian chytridiomycosis, have devastated affected populations. Fungal diseases are gaining recognition as significant causes of morbidity and mortality to plants, animals, and humans, yet fewer than 10% of fungal species are known. Furthermore, limited antifungal therapeutic drugs are available, antifungal therapeutics often have associated toxicity, and there are no approved antifungal vaccines. The unexpected emergence of WNS, the rapidity with which it has spread, and its unprecedented severity demonstrate both the impacts of novel fungal disease upon naïve host populations and challenges to effective management of such diseases.

Patient-Specific Pluripotent Stem Cells in Neurological Diseases

PubMed Central

Durnaoglu, Serpen; Genc, Sermin; Genc, Kursad

2011-01-01

Many human neurological diseases are not currently curable and result in devastating neurologic sequelae. The increasing availability of induced pluripotent stem cells (iPSCs) derived from adult human somatic cells provides new prospects for cellreplacement strategies and disease-related basic research in a broad spectrum of human neurologic diseases. Patient-specific iPSC-based modeling of neurogenetic and neurodegenerative diseases is an emerging efficient tool for in vitro modeling to understand disease and to screen for genes and drugs that modify the disease process. With the exponential increase in iPSC research in recent years, human iPSCs have been successfully derived with different technologies and from various cell types. Although there remain a great deal to learn about patient-specific iPSC safety, the reprogramming mechanisms, better ways to direct a specific reprogramming, ideal cell source for cellular grafts, and the mechanisms by which transplanted stem cells lead to an enhanced functional recovery and structural reorganization, the discovery of the therapeutic potential of iPSCs offers new opportunities for the treatment of incurable neurologic diseases. However, iPSC-based therapeutic strategies need to be thoroughly evaluated in preclinical animal models of neurological diseases before they can be applied in a clinical setting. PMID:21776279

Developing injectable immunoglobulins to treat cognitive impairment in Alzheimer's disease.

PubMed

Steinitz, Michael

2008-05-01

Alzheimer's disease is a devastating disorder, clinically characterized by a comprehensive cognitive decline. The novel strategy of anti-amyloid-beta immunotherapy has been suggested following encouraging results obtained in murine models of Alzheimer's disease, in non-human primates, and in small-scale clinical trials. To examine the choice between active or passive anti-amyloid-beta immunization and the choice of the molecule to which the immune machinery should be targeted, which are central issues in future immune therapy of Alzheimer's disease. Research into the new area of Alzheimer's disease immune therapy is primarily based on in vivo and in vitro studies of murine models of Alzheimer's disease. The studies are hence limited to defined genetic deficiencies. In humans, infusion of anti-amyloid-beta antibodies is considered a safer approach than active anti-amyloid-beta vaccination. Alzheimer's-disease-protective anti-amyloid-beta monoclonal antibodies should target specific epitopes within the amyloid beta(1 42) peptide, avoiding possibly harmful binding to the ubiquitous normal amyloid precursor protein. Since Alzheimer's disease immunotherapy requires repeated infusion of antibodies over a prolonged period of time, Alzheimer's disease patients will tolerate such antibodies provided the latter are exclusively of human origin. Human monoclonal antibodies that correspond to ubiquitous anti-amyloid-beta, present in all healthy humans, might bear important protective characteristics.

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy.

PubMed

Jastreboff, A M; Cymet, T

2002-04-01

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed.

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

PubMed Central

Jastreboff, A; Cymet, T

2002-01-01

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed. PMID:11930025

The missing calculation: the human cost.

PubMed

Green, Betty L

2007-01-01

The incursion of a foreign animal disease into any country produces devastating impacts on the country and on its producing industry. Although the associated financial losses to the country and its industry inevitably are calculated, the result in compensation to producers is often inadequate. Above and beyond the financial accounting calculations, however, there is a tremendously destructive and overwhelming impact that has been essentially ignored. That is the profound social impact and the real human cost to individual producers in the livestock industry and their families. Any decision to employ mass animal destruction as an animal disease control strategy must take this fundamental human element into full consideration. The author describes the consequences and depth of personal impact that the stamping-out approach has produced on affected individual livestock producers.

[Smallpox virus as biological weapon].

PubMed

Kondrusik, Maciej; Hermanowska-Szpakowicz, Teresa

2003-02-01

Smallpox, because of its high case-fatality rate, easy transmission from human to human, lack of specific treatment represents nowadays one of the main threats in bioterrorist attacks. Over the centuries, naturally occurring smallpox with its case-fatality over 30 percent and its ability to spread in any climate and season has been treated as the most dangerous infectious disease. But it is now, 25 years after the last documented case of smallpox and cessation of routine vaccination in present mobile and susceptible population, smallpox virus spread might be rapid and devastating.

Pandemic Threat Posed by Avian Influenza A Viruses

PubMed Central

Horimoto, Taisuke; Kawaoka, Yoshihiro

2001-01-01

Influenza pandemics, defined as global outbreaks of the disease due to viruses with new antigenic subtypes, have exacted high death tolls from human populations. The last two pandemics were caused by hybrid viruses, or reassortants, that harbored a combination of avian and human viral genes. Avian influenza viruses are therefore key contributors to the emergence of human influenza pandemics. In 1997, an H5N1 influenza virus was directly transmitted from birds in live poultry markets in Hong Kong to humans. Eighteen people were infected in this outbreak, six of whom died. This avian virus exhibited high virulence in both avian and mammalian species, causing systemic infection in both chickens and mice. Subsequently, another avian virus with the H9N2 subtype was directly transmitted from birds to humans in Hong Kong. Interestingly, the genes encoding the internal proteins of the H9N2 virus are genetically highly related to those of the H5N1 virus, suggesting a unique property of these gene products. The identification of avian viruses in humans underscores the potential of these and similar strains to produce devastating influenza outbreaks in major population centers. Although highly pathogenic avian influenza viruses had been identified before the 1997 outbreak in Hong Kong, their devastating effects had been confined to poultry. With the Hong Kong outbreak, it became clear that the virulence potential of these viruses extended to humans. PMID:11148006

Hypoxia as a therapy for mitochondrial disease.

PubMed

Jain, Isha H; Zazzeron, Luca; Goli, Rahul; Alexa, Kristen; Schatzman-Bone, Stephanie; Dhillon, Harveen; Goldberger, Olga; Peng, Jun; Shalem, Ophir; Sanjana, Neville E; Zhang, Feng; Goessling, Wolfram; Zapol, Warren M; Mootha, Vamsi K

2016-04-01

Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction. Copyright © 2016, American Association for the Advancement of Science.

History of Smallpox and Its Spread in Human Populations.

PubMed

Thèves, Catherine; Crubézy, Eric; Biagini, Philippe

2016-08-01

Smallpox is considered among the most devastating of human diseases. Its spread in populations, initiated for thousands of years following a probable transmission from an animal host, was concomitant with movements of people across regions and continents, trade and wars. Literature permitted to retrace the occurrence of epidemics from ancient times to recent human history, smallpox having affected all levels of past society including famous monarchs. The disease was officially declared eradicated in 1979 following intensive vaccination campaigns.Paleomicrobiology dedicated to variola virus is restricted to few studies, most unsuccessful, involving ancient material. Only one recent approach allowed the identification of viral DNA fragments from lung tissue of a 300-year-old body excavated from permafrost in Eastern Siberia; phylogenetic analysis revealed that this ancient strain was distinct from those described during the 20th century.

The Human Proteome Organization Chromosome 6 Consortium: integrating chromosome-centric and biology/disease driven strategies.

PubMed

Borchers, C H; Kast, J; Foster, L J; Siu, K W M; Overall, C M; Binkowski, T A; Hildebrand, W H; Scherer, A; Mansoor, M; Keown, P A

2014-04-04

The Human Proteome Project (HPP) is designed to generate a comprehensive map of the protein-based molecular architecture of the human body, to provide a resource to help elucidate biological and molecular function, and to advance diagnosis and treatment of diseases. Within this framework, the chromosome-based HPP (C-HPP) has allocated responsibility for mapping individual chromosomes by country or region, while the biology/disease HPP (B/D-HPP) coordinates these teams in cross-functional disease-based groups. Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins. Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences. The unique combination of genomic, proteomic, metabolomic, phenomic and health services data being drawn together within the Ch6 program has enormous potential to advance personalized medicine by promoting robust biomarkers, subunit vaccines and new drug targets. The strong liaison between the clinical and laboratory teams, and the structured framework for technology transfer and health policy decisions within Canada will increase the speed and efficacy of this transition, and the value of this translational research. Canada has been selected to play a leading role in the international Human Proteome Project, the global counterpart of the Human Genome Project designed to understand the structure and function of the human proteome in health and disease. Canada will lead an international team focusing on chromosome 6, which is functionally associated with more than 120 major human diseases, including immune and inflammatory disorders affecting the brain, skeletal system, heart and blood vessels, lungs, kidney, liver, gastrointestinal tract and endocrine system. Many of these chronic and persistent diseases have a high population prevalence, devastating clinical impact and profound societal consequences. As a result, they impose a multi-billion dollar economic burden on Canada and on all advanced societies through direct costs of patient care, the loss of health and productivity, and extensive caregiver burden. There is no definitive treatment at the present time for any of these disorders. The manuscript outlines the research which will involve a systematic assessment of all chromosome 6 genes, development of a knowledge base, and development of assays and reagents for all chromosome 6 proteins. We feel that the informatic infrastructure and MRM assays developed will place the chromosome 6 consortium in an excellent position to be a leading player in this major international research initiative. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes? © 2013.

Rift Valley Fever: An Emerging Mosquito-Borne Disease.

PubMed

Linthicum, Kenneth J; Britch, Seth C; Anyamba, Assaf

2016-01-01

Rift Valley fever (RVF), an emerging mosquito-borne zoonotic infectious viral disease caused by the RVF virus (RVFV) (Bunyaviridae: Phlebovirus), presents significant threats to global public health and agriculture in Africa and the Middle East. RVFV is listed as a select agent with significant potential for international spread and use in bioterrorism. RVFV has caused large, devastating periodic epizootics and epidemics in Africa over the past ∼60 years, with severe economic and nutritional impacts on humans from illness and livestock loss. In the past 15 years alone, RVFV caused tens of thousands of human cases, hundreds of human deaths, and more than 100,000 domestic animal deaths. Cattle, sheep, goats, and camels are particularly susceptible to RVF and serve as amplifying hosts for the virus. This review highlights recent research on RVF, focusing on vectors and their ecology, transmission dynamics, and use of environmental and climate data to predict disease outbreaks. Important directions for future research are also discussed.

Kinetoplastids: related protozoan pathogens, different diseases

PubMed Central

Stuart, Ken; Brun, Reto; Croft, Simon; Fairlamb, Alan; Gürtler, Ricardo E.; McKerrow, Jim; Reed, Steve; Tarleton, Rick

2008-01-01

Kinetoplastids are a group of flagellated protozoans that include the species Trypanosoma and Leishmania, which are human pathogens with devastating health and economic effects. The sequencing of the genomes of some of these species has highlighted their genetic relatedness and underlined differences in the diseases that they cause. As we discuss in this Review, steady progress using a combination of molecular, genetic, immunologic, and clinical approaches has substantially increased understanding of these pathogens and important aspects of the diseases that they cause. Consequently, the paths for developing additional measures to control these “neglected diseases” are becoming increasingly clear, and we believe that the opportunities for developing the drugs, diagnostics, vaccines, and other tools necessary to expand the armamentarium to combat these diseases have never been better. PMID:18382742

A universal vaccine for serogroup B meningococcus.

PubMed

Giuliani, Marzia M; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-07-18

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood.

Yellow fever: a reemerging threat.

PubMed

Gardner, Christina L; Ryman, Kate D

2010-03-01

Yellow fever (YF) is a viral disease, endemic to tropical regions of Africa and the Americas, which principally affects humans and nonhuman primates and is transmitted via the bite of infected mosquitoes. Yellow fever virus (YFV) can cause devastating epidemics of potentially fatal, hemorrhagic disease. Despite mass vaccination campaigns to prevent and control these outbreaks, the risk of major YF epidemics, especially in densely populated, poor urban settings, both in Africa and South America, has greatly increased. Consequently, YF is considered an emerging, or reemerging disease of considerable importance. This article comprehensively reviews the history, microbiology, epidemiology, clinical presentation, diagnosis, and treatment of YFV, as well as the vaccines produced to combat YF. 2010 Elsevier Inc. All rights reserved.

Lead Exposure in the Special Operations Shooter How to Prevent Cognitive Decline and Permanent Disability.

PubMed

Brandon, Jonathan W; Solarczyk, Justin K; Durrani, Timur S

Lead toxicity is an important environmental disease and its effects on the human body can be devastating. Unique exposures to Special Operations Forces personnel may include use of firing ranges, use of automotive fuels, production of ammunition, and bodily retention of bullets. Toxicity may degrade physical and psychological fitness, and cause long-term negative health outcomes. Specific effects on fine motor movements, reaction times, and global function could negatively affect shooting skills and decision-making. Biologic monitoring and chelation treatment are poor solutions for protecting this population. Through primary prevention, Special Operations Forces personnel can be protected, in any environment, from the devastating effects of lead exposure. This article offers tools to physicians, environmental service officers, and Special Operations Medics for primary prevention of lead poisoning in the conventional and the austere or forward deployed environments. 2018.

[The plague].

PubMed

Carniel, Elisabeth

2002-08-01

The plague has been one of the most devastating diseases of human history. Despite major advances in diagnosis, prevention, and treatment, it has not been possible to eradicate this infection. Plague is still active in Africa, in Asia and in the Americas, and is classified as a currently re-emerging disease. The plague is mainly a disease of rodents, which is transmitted by fleabites. Humans develop two main clinical forms: bubonic plague (following bites of infected fleas, lethal in 50-70% of the cases in less than a week if an appropriate treatment is not started rapidly), and pneumonic plague (after inhalation of infected droplets, lethal in less than three days in 100% of cases without immediate treatment). Y. pestis, the causative agent of plague, is usually sensitive to most antibiotics, but the first multi-resistant strain was recently described. No efficient and safe vaccines are currently available. The plague bacillus is one of the few organisms that could be used for biological warfare.

Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell–mediated dendrite and synapse loss

PubMed Central

Kreutzfeldt, Mario; Bergthaler, Andreas; Fernandez, Marylise; Brück, Wolfgang; Steinbach, Karin; Vorm, Mariann; Coras, Roland; Blümcke, Ingmar; Bonilla, Weldy V.; Fleige, Anne; Forman, Ruth; Müller, Werner; Becher, Burkhard; Misgeld, Thomas; Kerschensteiner, Martin; Pinschewer, Daniel D.

2013-01-01

Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8+ T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model in mice, disease depended on CTL-derived interferon-γ (IFN-γ) and neuronal IFN-γ signaling. Downstream STAT1 phosphorylation and nuclear translocation in neurons were associated with dendrite and synapse loss (deafferentation). Analogous molecular and structural alterations were also found in human Rasmussen encephalitis, a CTL-mediated human autoimmune disorder of the CNS. Importantly, therapeutic intervention by IFN-γ blocking antibody prevented neuronal deafferentation and clinical disease without reducing CTL responses or CNS infiltration. These findings identify neuronal IFN-γ signaling as a novel target for neuroprotective interventions in CTL-mediated CNS disease. PMID:23999498

The Impact of the Milk Glycobiome on the Neonate Gut Microbiota

PubMed Central

Pacheco, Alline R.; Barile, Daniela; Underwood, Mark A.; Mills, David A.

2015-01-01

Human milk is a complete source of nourishment for the infant. Exclusive breastfeeding not only sustains the infant’s development but also guides the proliferation of a protective intestinal microbiota. Among the many components of milk that modulate the infant gut microbiota, the milk glycans, which comprise free oligosaccharides, glycoproteins, and glycolipids, are increasingly recognized as drivers of microbiota development and overall gut health. These glycans may display pleiotropic functions, conferring protection against infectious diseases and also acting as prebiotics, selecting for the growth of beneficial intestinal bacteria. The prebiotic effect of milk glycans has direct application to prevention of diseases such as necrotizing enterocolitis, a common and devastating disease of preterm infants. In this article, we review the impact of the human (and bovine) milk glycome on gut health through establishment of a milk-oriented microbiota in the neonate. PMID:25387230

Determinants of initiation and progression of idiopathic pulmonary fibrosis

PubMed Central

Kottmann, Robert Matthew; Hogan, Christopher M.; Phipps, Richard P.; Sime, Patricia J.

2013-01-01

IPF is a devastating disease with few therapeutic options. The precise aetiology of IPF remains elusive. However, our understanding of the pathologic processes involved in the initiation and progression of this disease is improving. Data on the mechanisms underlying IPF have been generated from epidemiologic investigations as well as cellular and molecular studies of human tissues. Although no perfect animal model of human IPF exists, pre-clinical animal studies have helped define pathways which are likely important in human disease. Epithelial injury, fibroblast activation and repetitive cycles of injury and abnormal repair are almost certainly key events. Factors which have been associated with initiation and/or progression of IPF include viral infections, abnormal cytokine, chemokine and growth factor production, oxidant stress, autoimmunity, inhalational of toxicants and gastro-oesophageal reflux disease. Furthermore, recent evidence identifies a role for a variety of genetic and epigenetic abnormalities ranging from mutations in surfactant protein C to abnormalities in telomere length and telomerase activity. The challenge remains to identify additional inciting agents and key dysregulated pathways that lead to disease progression so that we can develop targeted therapies to treat or prevent this serious disease. PMID:19740254

Remote monitoring of the progression of primary pneumonic plague in Brown Norway rats in high-capacity, high-containment housing

PubMed Central

Coate, Eric A.; Kocsis, Andrew G.; Peters, Kristen N.; Anderson, Paul E.; Ellersieck, Mark R.; Fine, Deborah M.; Anderson, Deborah M.

2014-01-01

Development of new vaccines, diagnostics and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. To overcome this experimental gap, the U.S. Food and Drug Administration established the Animal Rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large scale clinical trials for diseases with limited natural human incidence. In this report, we evaluated the Brown Norway rat as a model for pneumonic plague and describe the natural history of clinical disease following inhalation exposure to Yersinia pestis. In high-capacity, high-containment housing, we monitored temperature, activity, heart rate and rhythm by capturing electronic impulses transmitted from abdominal telemeter implants. Using this system, we show that reduced activity and development of fever are sensitive indications of disease progression. Furthermore, we identified heart arrhythmias as contributing factors to the rapid progression to lethality following the fever response. Together these data validate the Brown Norway rat as an experimental model for human pneumonic plague and provide new insight that may ultimately lead to novel approaches in post-exposure treatment of this devastating infection. PMID:24719212

Genomics of Clostridium

NASA Astrophysics Data System (ADS)

Jacobson, Mark Joseph; Johnson, Eric A.

The clostridia have a rich history and contemporary importance in industrial, environmental, and medical microbiology. Due to their ability to form endospores, clostridia are ubiquitous in nature and are found in many environments, especially in soils and the intestinal tract of animals including humans. Many clostridia cause devastating diseases of humans and animals, such as botulism, tetanus, and gas gangrene, through the production of protein toxins. The clostridia produce more protein toxins that are lethal for humans and animals than any other bacterial genus (Johnson, 2005; Van Heyningen, 1950). Other species are important in the formation of solvents and organic acids by anaerobic fermentations or as a source of unique enzymes for biocatalysis (Bradshaw and Johnson, 2010; Hatheway and Johnson, 1998).

IRS-PCR-based genetic mapping of the huntingtin interacting protein gene (HIP1) on mouse chromosome 5.

PubMed

Himmelbauer, H; Wedemeyer, N; Haaf, T; Wanker, E E; Schalkwyk, L C; Lehrach, H

1998-01-01

Huntington's disease (HD) is a devastating central nervous system disorder. Even though the gene responsible has been positionally cloned recently, its etiology has remained largely unclear. To investigate potential disease mechanisms, we conducted a search for binding partners of the HD-protein huntingtin. With the yeast two-hybrid system, one such interacting factor, the huntingtin interacting protein-1 (HIP-1), was identified (Wanker et al. 1997; Kalchman et al. 1997) and the human gene mapped to 7q11.2. In this paper we demonstrate the localization of the HIP1 mouse homologue (Hip1) into a previously identified region of human-mouse synteny on distal mouse Chromosome (Chr) 5, both employing an IRS-PCR-based mapping strategy and traditional fluorescent in situ hybridization (FISH) mapping.

Use of digital PCR to improve early detection of CLas infection

USDA-ARS?s Scientific Manuscript database

Huanglongbing is a devastating disease of citrus caused by the bacterium Candidatus Liberibacter asiaticus. Huanglongbing has devastated the Florida citrus industry and is threatening citrus in Texas and California. Detection of Candidatus Liberibacter asiaticus infections as early as possible is ...

Human health implications of avian influenza viruses and paramyxoviruses.

PubMed

Capua, I; Alexander, D J

2004-01-01

Among avian influenza viruses and avian paramyxoviruses are the aetiological agents of two of the most devastating diseases of the animal kingdom: (i). the highly pathogenic form of avian influenza, caused by some viruses of the H5 and H7 subtypes, and (ii). Newcastle disease, caused by virulent strains of APMV type 1. Mortality rates due to these agents can exceed 50% in naïve bird populations, and, for some strains of AI, nearly 100%. These viruses may also be responsible for clinical conditions in humans. The virus responsible for Newcastle disease has been known to cause conjunctivitis in humans since the 1940s. The conjunctivitis is self-limiting and does not have any permanent consequences. Until 1997, reports of human infection with avian influenza viruses were sporadic and frequently associated with conjunctivitis. Recently, however, avian influenza virus infections have been associated with fatalities in human beings. These casualties have highlighted the potential risk that this type of infection poses to public health. In particular, the pathogenetic mechanisms of highly pathogenic avian influenza viruses in birds and the possibility of reassortment between avian and human viruses in the human host represent serious threats to human health. For this reason, any suspected case should be investigated thoroughly.

Is it worth a dam?

PubMed Central

Joyce, S

1997-01-01

Once a sign of modernization and growth, dams are often seen today as symbols of environmental and social devastation. Over 800,000 dams have been built worldwide to provide drinking water, flood control, hydropower, irrigation, navigation, and water storage. Dams do indeed provide these things,but at the cost of several adverse, unexpected effects: disruption of ecosystems, decline of fish stocks, forced human and animal resettlements, and diseases such as malaria, which are borne by vectors that thrive in quiet waters. PMID:9349830

Ferritin for the Clinician

PubMed Central

Knovich, Mary Ann; Storey, Jonathan A.; Coffman, Lan G.; Torti, Suzy V.

2009-01-01

Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage. PMID:18835072

Understanding mechanisms and seeking cures for Alzheimer's disease: why we must be "extraordinarily diverse".

PubMed

Thambisetty, Madhav

2017-10-01

After more than a century since Dr. Alois Alzheimer first described the pathological hallmarks accompanying the defining clinical features of the disease, we have yet to deliver any meaningful disease-modifying treatments to our patients. In this article, I present a rationale for the need to be "extraordinarily diverse" in seeking effective ways to treat or prevent this devastating disease. This approach is based on applying a systems-biology perspective at the population level, using a diverse array of "OMICS" methodologies to identify molecular mechanisms associated with well-established AD risk factors including systemic inflammation, obesity, and insulin resistance. We believe that applying this strategy to understand longitudinal changes in human physiology during aging is of paramount importance in identifying meaningful opportunities to intervene effectively in AD.

Novel Insights into Cell Entry of Emerging Human Pathogenic Arenaviruses.

PubMed

Fedeli, Chiara; Moreno, Héctor; Kunz, Stefan

2018-06-22

Viral hemorrhagic fevers caused by emerging RNA viruses of the Arenavirus family are among the most devastating human diseases. Climate change, global trade, and increasing urbanization promote the emergence and re-emergence of these human pathogenic viruses. Emerging pathogenic arenaviruses are of zoonotic origin and reservoir-to-human transmission is crucial for spillover into human populations. Host cell attachment and entry are the first and most fundamental steps of every virus infection and represent major barriers for zoonotic transmission. During host cell invasion, viruses critically depend on cellular factors, including receptors, co-receptors, and regulatory proteins of endocytosis. An in-depth understanding of the complex interaction of a virus with cellular factors implicated in host cell entry is therefore crucial to predict the risk of zoonotic transmission, define the tissue tropism, and assess disease potential. Over the past years, investigation of the molecular and cellular mechanisms underlying host cell invasion of human pathogenic arenaviruses uncovered remarkable viral strategies and provided novel insights into viral adaptation and virus-host co-evolution that will be covered in the present review. Copyright © 2018. Published by Elsevier Ltd.

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases

PubMed Central

Sokolow, S. H.; Ngonghala, C. N.; Jocque, M.; Lund, A.; Barry, M.; Mordecai, E. A.; Daily, G. C.; Andrews, J. R.; Bendavid, E.; Luby, S. P.; LaBeaud, A. D.; Seetah, K.; Guégan, J. F.; De Leo, G. A.

2017-01-01

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’. PMID:28438917

A universal vaccine for serogroup B meningococcus

PubMed Central

Giuliani, Marzia M.; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-01-01

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood. PMID:16825336

Microbial Vertical Transmission during Human Pregnancy.

PubMed

Arora, Nitin; Sadovsky, Yoel; Dermody, Terence S; Coyne, Carolyn B

2017-05-10

Congenital infections with pathogens such as Zika virus, Toxoplasma gondii, Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity and mortality worldwide. Despite the devastating impact of microbial infections on the developing fetus, relatively little is known about how pathogens associated with congenital disease breach the placental barrier to transit vertically during human pregnancy. In this Review, we focus on transplacental transmission of pathogens during human gestation. We introduce the structure of the human placenta and describe the innate mechanisms by which the placenta restricts microbial access to the intrauterine compartment. Based on current knowledge, we also discuss the potential pathways employed by microorganisms to overcome the placental barrier and prospects for the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Neglected parasitic infections in the United States: toxocariasis.

PubMed

Woodhall, Dana M; Eberhard, Mark L; Parise, Monica E

2014-05-01

Toxocariasis is a preventable parasitic disease that is caused by the dog and cat roundworms Toxocara cani and T. cati, respectively. Humans become infected when they accidently ingest infectious Toxocara eggs commonly found in contaminated soil; children are most often affected. Clinical manifestations of Toxocara infection in humans include ocular toxocariasis and visceral toxocariasis. Although infection with Toxocara can cause devastating disease, the burden of toxocariasis in the United States population remains unknown. In addition, risk factors for acquiring infection need to be better defined, and research needs to be conducted to better understand the pathophysiology and clinical course of toxocariasis. Development of diagnostic tests would enable clinicians to detect active infection, and determination of optimal drug regiments would ensure patients were appropriately treated. Addressing these public health gaps is necessary to understand and address the impact of toxocariasis in the United States.

The history of epidemic typhus.

PubMed

Raoult, Didier; Woodward, Theodore; Dumler, J Stephen

2004-03-01

Few infectious diseases have influenced human civilization to the same degree as louse-transmitted typhus. Rickettsia prowazekii continues to strikes tens to hundreds of thousands of persons who live with war, famine, crowding, and in squalid conditions associated with social unrest, with mortality rates in excess of 10% to 15%. Historical documents confirm that such devastation has been a continuous feature of human existence to the extent that typhus has been a major determinant in the outcome of many wars, altering human history in its wake-despite incomplete knowledge of its precise origin. In the twenty-first century, circumstances are still conductive for outbreak; the emerging threat of bioterrorism raises justifiable concerns that typhus could affect civilization just as greatly in the future as it has in the past.

The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

PubMed

Harel, Itamar; Brunet, Anne

2015-01-01

Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients

PubMed Central

Mazcko, Christina; Brown, Diane E.; Koehler, Jennifer W.; Miller, Andrew D.; Miller, C. Ryan; Bentley, R. Timothy; Packer, Rebecca A.; Breen, Matthew; Boudreau, C. Elizabeth; Levine, Jonathan M.; Simpson, R. Mark; Halsey, Charles; Kisseberth, William; Rossmeisl, John H.; Dickinson, Peter J.; Fan, Timothy M.; Corps, Kara; Aldape, Kenneth; Puduvalli, Vinay; Pluhar, G. Elizabeth; Gilbert, Mark R.

2016-01-01

On September 14–15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed. PMID:27179361

Vibrational duetting mimics to trap and disrupt mating of the devastating Asian citrus psyllid insect pest

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid (ACP) is the primary vector of a bacterium that produces a devastating disease of citrus, huanglongbing. Efficient surveillance of ACP at low population densities is essential for timely pest management programs. ACP males search for mates on tree branches by producing vibra...

[Contribution of the rapid diagnostic tests for infectious diseases to the patient management in the Great East Japan earthquake].

PubMed

Hatta, Masumitsu; Kaku, Mitsuo

2012-01-01

On 11 March 2011, an earthquake measuring 9.0 on the Richter scale off the northeast coast of Honshu Island, Japan, produced a devastating tsunami that destroyed many towns and villages near the coast in Iwate, Miyagi, and Fukushima prefectures. Miyagi Prefecture was the area most severely devastated by the tsunami, with extensive loss of life and property; hundreds of thousands of people lost their houses and were forced to move to evacuation areas. In the days and weeks following devastating natural disasters, the threat of infectious disease outbreak is high. Rapid diagnostic tests can be performed at or near the site of patient care and the tests were very useful in this disaster, because they enabled us to manage patients appropriately in the settings where medical resources were limited. Here we report actual cases where the rapid diagnostic tests for infectious diseases were useful in the patient management.

Population structure of the Chagas disease vector, Triatoma infestans, at the urban-rural interface

PubMed Central

Foley, Erica A.; Khatchikian, Camilo E.; Hwang, Josephine; Ancca-Juárez, Jenny; Borrini-Mayori, Katty; Quıspe-Machaca, Victor R.; Levy, Michael Z.; Brisson, Dustin

2013-01-01

The increasing rate of biological invasions resulting from human transport or human-mediated changes to the environment have had devastating ecologic and public health consequences. The kissing bug, Triatoma infestans, has dispersed through the Peruvian city of Arequipa. The biological invasion of this insect has resulted in a public health crisis, putting thousands of residents of this city at risk of infection by Trypanosoma cruzi and subsequent development of Chagas disease. Here we show that populations of Tria. Infestans in geographically distinct districts within and around this urban center share a common recent evolutionary history although current gene flow is restricted even between proximal sites. The population structure among the Tria. Infestans in different districts is not correlated with the geographic distance between districts. These data suggest that migration among the districts is mediated by factors beyond the short-range migratory capabilities of Tria. Infestans and that human movement has played a significant role in the structuring of the Tria. Infestans population in the region. Rapid urbanization across southern South America will continue to create suitable environments for Tria. Infestans and knowledge of its urban dispersal patterns may play a fundamental role in mitigating human disease risk. PMID:24103030

Use of a surgical helmet system to minimize splash injury during percutaneous renal surgery in high-risk patients.

PubMed

Eandi, Jonathan A; Nanigian, Dana K; Smith, William H; Low, Roger K

2008-12-01

The transmission risk to surgeons performing percutaneous renal surgery on patients who are infected with human immunodeficiency virus/acquired immunodeficiency syndrome, hepatitis B, or hepatitis C is unknown. A recent study found 55% of surgeons' masks contain evidence of blood splash contamination after percutaneous nephrolithotomy. While the risk of infectious disease transmission to the surgeon after mucocutaneous exposure is unknown, the incapacitating disease these pathogens cause can have a devastating and permanent effect on a surgeon's career. We describe our use of a surgical helmet system when performing percutaneous renal surgery on high-risk patients to minimize risk of splash injury and transmission of blood-borne pathogens.

The past, present, and future of Leishmania genomics and transcriptomics

PubMed Central

Cantacessi, Cinzia; Dantas-Torres, Filipe; Nolan, Matthew J.; Otranto, Domenico

2015-01-01

It has been nearly 10 years since the completion of the first entire genome sequence of a Leishmania parasite. Genomic and transcriptomic analyses have advanced our understanding of the biology of Leishmania, and shed new light on the complex interactions occurring within the parasite–host–vector triangle. Here, we review these advances and examine potential avenues for translation of these discoveries into treatment and control programs. In addition, we argue for a strong need to explore how disease in dogs relates to that in humans, and how an improved understanding in line with the ‘One Health’ concept may open new avenues for the control of these devastating diseases. PMID:25638444

Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

PubMed

Osheroff, Neil

2006-10-01

Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.

N-myristoyltransferase inhibitors as new leads to treat sleeping sickness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frearson, Julie A.; Brand, Stephen; McElroy, Stuart P.

2010-11-05

African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for {approx}30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target - T. brucei N-myristoyltransferase - leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis inmore » mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis.« less

[When history meets molecular medicine: molecular history of human tuberculosis].

PubMed

Ottini, Laura; Falchetti, Mario

2010-01-01

Tuberculosis represents one of the humankind's most socially devastating diseases. Despite a long history of medical research and the development of effective therapies, this disease remains a global health danger even in the 21st century. Tuberculosis may cause death but infected people with effective immunity may remain healthy for years, suggesting long-term host-pathogen co-existence. Because of its antiquity, a supposed association with human settlements and the tendency to leave typical lesions on skeletal and mummified remains, tuberculosis has been the object of intensive multidisciplinary studies, including paleo-pathological research. During the past 10 years molecular paleo-pathology developed as a new scientific discipline allowing the study of ancient pathogens by direct detection of their DNA. In this work, we reviewed evidences for tuberculosis in ancient human remains, current methods for identifying ancient mycobacterial DNA and explored current theories of Mycobacterium tuberculosis evolution and their implications in the global development of tuberculosis looking into the past and present at the same time.

Rapid evolutionary response to a transmissible cancer in Tasmanian devils

PubMed Central

Epstein, Brendan; Jones, Menna; Hamede, Rodrigo; Hendricks, Sarah; McCallum, Hamish; Murchison, Elizabeth P.; Schönfeld, Barbara; Wiench, Cody; Hohenlohe, Paul; Storfer, Andrew

2016-01-01

Although cancer rarely acts as an infectious disease, a recently emerged transmissible cancer in Tasmanian devils (Sarcophilus harrisii) is virtually 100% fatal. Devil facial tumour disease (DFTD) has swept across nearly the entire species' range, resulting in localized declines exceeding 90% and an overall species decline of more than 80% in less than 20 years. Despite epidemiological models that predict extinction, populations in long-diseased sites persist. Here we report rare genomic evidence of a rapid, parallel evolutionary response to strong selection imposed by a wildlife disease. We identify two genomic regions that contain genes related to immune function or cancer risk in humans that exhibit concordant signatures of selection across three populations. DFTD spreads between hosts by suppressing and evading the immune system, and our results suggest that hosts are evolving immune-modulated resistance that could aid in species persistence in the face of this devastating disease. PMID:27575253

Neglected Parasitic Infections in the United States: Toxocariasis

PubMed Central

Woodhall, Dana M.; Eberhard, Mark L.; Parise, Monica E.

2014-01-01

Toxocariasis is a preventable parasitic disease that is caused by the dog and cat roundworms Toxocara cani and T. cati, respectively. Humans become infected when they accidently ingest infectious Toxocara eggs commonly found in contaminated soil; children are most often affected. Clinical manifestations of Toxocara infection in humans include ocular toxocariasis and visceral toxocariasis. Although infection with Toxocara can cause devastating disease, the burden of toxocariasis in the United States population remains unknown. In addition, risk factors for acquiring infection need to be better defined, and research needs to be conducted to better understand the pathophysiology and clinical course of toxocariasis. Development of diagnostic tests would enable clinicians to detect active infection, and determination of optimal drug regiments would ensure patients were appropriately treated. Addressing these public health gaps is necessary to understand and address the impact of toxocariasis in the United States. PMID:24808249

Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases.

PubMed

Garchitorena, A; Sokolow, S H; Roche, B; Ngonghala, C N; Jocque, M; Lund, A; Barry, M; Mordecai, E A; Daily, G C; Jones, J H; Andrews, J R; Bendavid, E; Luby, S P; LaBeaud, A D; Seetah, K; Guégan, J F; Bonds, M H; De Leo, G A

2017-06-05

Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Author(s).

Genome Editing: A New Approach to Human Therapeutics.

PubMed

Porteus, Matthew

2016-01-01

The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

AIDS, Avian flu, SARS, MERS, Ebola, Zika… what next?

PubMed

Reperant, Leslie A; Osterhaus, Albert D M E

2017-08-16

Emerging infections have threatened humanity since times immemorial. The dramatic anthropogenic, behavioral and social changes that have affected humanity and the environment in the past century have accelerated the intrusion of novel pathogens into the global human population, sometimes with devastating consequences. The AIDS and influenza pandemics have claimed and will continue to claim millions of lives. The recent SARS and Ebola epidemics have threatened populations across borders. The emergence of MERS may well be warning signals of a nascent pandemic threat, while the potential for geographical spread of vector-borne diseases, such as Zika, but also Dengue and Chikungunya is unprecedented. Novel technologies and innovative approaches have multiplied to address and improve response preparedness towards the increasing yet unpredictable threat posed by emerging pathogens. Copyright © 2017. Published by Elsevier Ltd.

Host response to Brucella infection: review and future perspective.

PubMed

Elfaki, Mohamed G; Alaidan, Alwaleed Abdullah; Al-Hokail, Abdullah Abdulrahman

2015-07-30

Brucellosis is a zoonotic and contagious infectious disease caused by infection with Brucella species. The infecting brucellae are capable of causing a devastating multi-organ disease in humans with serious health complications. The pathogenesis of Brucella infection is influenced largely by host factors, Brucella species/strain, and the ability of invading brucellae to survive and replicate within mononuclear phagocytic cells, preferentially macrophages (Mf). Consequently, the course of human infection may appear as an acute fatal or progress into chronic debilitating infection with periodical episodes that leads to bacteremia and death. The existence of brucellae inside Mf represents one of the strategies used by Brucella to evade the host immune response and is responsible for treatment failure in certain human populations treated with anti-Brucella drugs. Moreover, the persistence of brucellae inside Mf complicates the diagnosis and may affect the host cell signaling pathways with consequent alterations in both innate and adaptive immune responses. Therefore, there is an urgent need to pursue the development of novel drugs and/or vaccine targets against human brucellosis using high throughput technologies in genomics, proteomics, and immunology.

Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity.

PubMed

Sorrentino, Vincenzo; Romani, Mario; Mouchiroud, Laurent; Beck, John S; Zhang, Hongbo; D'Amico, Davide; Moullan, Norman; Potenza, Francesca; Schmid, Adrien W; Rietsch, Solène; Counts, Scott E; Auwerx, Johan

2017-12-14

Alzheimer's disease is a common and devastating disease characterized by aggregation of the amyloid-β peptide. However, we know relatively little about the underlying molecular mechanisms or how to treat patients with Alzheimer's disease. Here we provide bioinformatic and experimental evidence of a conserved mitochondrial stress response signature present in diseases involving amyloid-β proteotoxicity in human, mouse and Caenorhabditis elegans that involves the mitochondrial unfolded protein response and mitophagy pathways. Using a worm model of amyloid-β proteotoxicity, GMC101, we recapitulated mitochondrial features and confirmed that the induction of this mitochondrial stress response was essential for the maintenance of mitochondrial proteostasis and health. Notably, increasing mitochondrial proteostasis by pharmacologically and genetically targeting mitochondrial translation and mitophagy increases the fitness and lifespan of GMC101 worms and reduces amyloid aggregation in cells, worms and in transgenic mouse models of Alzheimer's disease. Our data support the relevance of enhancing mitochondrial proteostasis to delay amyloid-β proteotoxic diseases, such as Alzheimer's disease.

[Cooperation and support activities of infection control after the Great East Japan Earthquake].

PubMed

Hatta, Masumitsu; Kaku, Mitsuo

2013-12-01

On 11 March 2011, an earthquake measuring 9.0 on the Richter scale occurred off the northeast coast of Honshu Island, Japan, produced a devastating tsunami that destroyed many towns and villages near the coast in Iwate, Miyagi, and Fukushima prefectures. Miyagi Prefecture was the area most severely devastated by the tsunami, with extensive loss of life and property; hundreds of thousands of people lost their houses and were forced to move to evacuation areas. In the days and weeks following devastating natural disasters, the threat of infectious disease outbreak is high. We initiated cooperation and support activities in terms of infection control at evacuation centers in the aftermath of the disaster. For example, we assessed sanitary and infectious risk factors in evacuation centers, in collaboration with Miyagi Prefectural Government and public health centers in the devastated area, to prevent the transmission of infectious diseases among evacuees. We also supported the control of two outbreaks of influenza A, which occurred in different centers in Miyagi Prefecture in the early period after the disaster. Both outbreaks subsided without any complicated or fatal cases of influenza as a result of the prompt implementation of a systemic approach with a bundle of control measures.

Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy

PubMed Central

Wang, Zhi-Bo; Zhang, Xiaoqing; Li, Xue-Jun

2013-01-01

Establishing human cell models of spinal muscular atrophy (SMA) to mimic motor neuron-specific phenotypes holds the key to understanding the pathogenesis of this devastating disease. Here, we developed a closely representative cell model of SMA by knocking down the disease-determining gene, survival motor neuron (SMN), in human embryonic stem cells (hESCs). Our study with this cell model demonstrated that knocking down of SMN does not interfere with neural induction or the initial specification of spinal motor neurons. Notably, the axonal outgrowth of spinal motor neurons was significantly impaired and these disease-mimicking neurons subsequently degenerated. Furthermore, these disease phenotypes were caused by SMN-full length (SMN-FL) but not SMN-Δ7 (lacking exon 7) knockdown, and were specific to spinal motor neurons. Restoring the expression of SMN-FL completely ameliorated all of the disease phenotypes, including specific axonal defects and motor neuron loss. Finally, knockdown of SMN-FL led to excessive mitochondrial oxidative stress in human motor neuron progenitors. The involvement of oxidative stress in the degeneration of spinal motor neurons in the SMA cell model was further confirmed by the administration of N-acetylcysteine, a potent antioxidant, which prevented disease-related apoptosis and subsequent motor neuron death. Thus, we report here the successful establishment of an hESC-based SMA model, which exhibits disease gene isoform specificity, cell type specificity, and phenotype reversibility. Our model provides a unique paradigm for studying how motor neurons specifically degenerate and highlights the potential importance of antioxidants for the treatment of SMA. PMID:23208423

Ergot: from witchcraft to biotechnology.

PubMed

Haarmann, Thomas; Rolke, Yvonne; Giesbert, Sabine; Tudzynski, Paul

2009-07-01

The ergot diseases of grasses, caused by members of the genus Claviceps, have had a severe impact on human history and agriculture, causing devastating epidemics. However, ergot alkaloids, the toxic components of Claviceps sclerotia, have been used intensively (and misused) as pharmaceutical drugs, and efficient biotechnological processes have been developed for their in vitro production. Molecular genetics has provided detailed insight into the genetic basis of ergot alkaloid biosynthesis and opened up perspectives for the design of new alkaloids and the improvement of production strains; it has also revealed the refined infection strategy of this biotrophic pathogen, opening up the way for better control. Nevertheless, Claviceps remains an important pathogen worldwide, and a source for potential new drugs for central nervous system diseases.

International collaborations to facilitate a better understanding of Newcastle disease epidemiology

USDA-ARS?s Scientific Manuscript database

Infections of poultry species with virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), worldwide one of the most economically significant and devastating diseases for poultry producers. Biological engagement programs (BEP) between the Southeast Poultry Research Laborator...

The Role of Exosomal VP40 in Ebola Virus Disease.

PubMed

Pleet, Michelle L; DeMarino, Catherine; Lepene, Benjamin; Aman, M Javad; Kashanchi, Fatah

2017-04-01

Ebola virus (EBOV) can cause a devastating hemorrhagic disease, leading to death in a short period of time. After infection, the resulting EBOV disease results in high levels of circulating cytokines, endothelial dysfunction, coagulopathy, and bystander lymphocyte apoptosis in humans and nonhuman primates. The VP40 matrix protein of EBOV is essential for viral assembly and budding from the host cell. Recent data have shown that VP40 exists in the extracellular environment, including in exosomes, and exosomal VP40 can impact the viability of recipient immune cells, including myeloid and T cells, through the regulation of the RNAi and endosomal sorting complexes required for transport pathways. In this study, we discuss the latest findings of the impact of exosomal VP40 on immune cells in vitro and its potential implications for pathogenesis in vivo.

Newcastle disease virus infection in quail

USDA-ARS?s Scientific Manuscript database

Newcastle disease (ND), caused by virulent strains of Newcastle disease virus (NDV), is a devastating disease of poultry worldwide. The pathogenesis of ND in quail is poorly documented. To characterize the ability of virulent NDV strains to replicate and cause disease in quail, groups of 14 two-week...

Progression of pathogenic events in cynomolgus macaques infected with variola virus.

PubMed

Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

Population structure of the Chagas disease vector, Triatoma infestans, at the urban-rural interface.

PubMed

Foley, Erica A; Khatchikian, Camilo E; Hwang, Josephine; Ancca-Juárez, Jenny; Borrini-Mayori, Katty; Quıspe-Machaca, Victor R; Levy, Michael Z; Brisson, Dustin

2013-10-01

The increasing rate of biological invasions resulting from human transport or human-mediated changes to the environment has had devastating ecological and public health consequences. The kissing bug, Triatoma infestans, has dispersed through the Peruvian city of Arequipa. The biological invasion of this insect has resulted in a public health crisis, putting thousands of residents of this city at risk of infection by Trypanosoma cruzi and subsequent development of Chagas disease. Here, we show that populations of Tria. infestans in geographically distinct districts within and around this urban centre share a common recent evolutionary history although current gene flow is restricted even between proximal sites. The population structure among the Tria. infestans in different districts is not correlated with the geographical distance between districts. These data suggest that migration among the districts is mediated by factors beyond the short-range migratory capabilities of Tria. infestans and that human movement has played a significant role in the structuring of the Tria. infestans population in the region. Rapid urbanization across southern South America will continue to create suitable environments for Tria. infestans, and knowledge of its urban dispersal patterns may play a fundamental role in mitigating human disease risk. © 2013 John Wiley & Sons Ltd.

Pathological and phylogenetic characterization of Newcastle disease viruses from Israel and Pakistan

USDA-ARS?s Scientific Manuscript database

Newcastle disease (ND) is a devastating disease of poultry worldwide caused by virulent strains of Newcastle disease virus (NDV). New strains of NDV frequently emerge, creating challenges for disease control. Since 2012, NDV strains of new genotype VIIi have been reported in Israel and Pakistan, b...

Subacute sclerosing panencephalitis (SSPE) the story of a vanishing disease.

PubMed

Gadoth, Natan

2012-10-01

Subacute sclerosing panencephalitis (SSPE), is a devastating "slow virus" brain disease which affects young children who had measles some 6-7 years earlier. Although, the pandemic of SSPE during 1960-1980's was almost eradicated due to mass immunization, the disease is still taking the life of young children in countries where measles immunization is incomplete and in world regions where genetic polymorphism to this particular infection is present. The present review was written for the fortunate young generation of pediatricians and pediatric neurologists who probably have not seen a case of SSPE during their career, and for those who work in counties where the disease has not been eradicated. It is also a reminder that with full coverage of measles immunization this devastating disease can be fully eradicated. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Drosophila as an In Vivo Model for Human Neurodegenerative Disease

PubMed Central

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

Drosophila as an In Vivo Model for Human Neurodegenerative Disease.

PubMed

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

2015-10-01

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. Copyright © 2015 by the Genetics Society of America.

The Soriano Award Lecture. Emerging infections of the nervous system.

PubMed

Johnson, R T

1994-06-01

The epidemic of acquired immunodeficiency disease [AIDS] has focused interest on the origins of "new" infectious agents. Great plagues are well known from the distant past, but a number of novel diseases affecting the nervous system infections have emerged in recent years. The causes of such new disorders are diverse: whereas rapid mutations of microbes allow the evolution of truly novel agents, the appearance of new diseases is more often due to changes in human or vector populations or changes in societal mores that result in dissemination of preexistent microbes. Examples of recently emerging infections that involve the nervous system include the enterovirus 70 epidemics with poliomyelitis-like disease, the appearance of California virus encephalitis in the midwestern United States, the rapid spread of Lyme disease with its many neurological complications in the eastern United States, and the outbreak of bovine spongiform encephalopathy in the United Kingdom, in addition to the devastating epidemic of human immunodeficiency virus (HIV), which will cause nervous system disease in over half of those infected. As the world population increases and modern transportation brings us closer into a "global village" more new agents will emerge and more will be sustained. Knowledge of the molecular biology and ecology of the agents and awareness of how our actions can alter their behavior are our best defense.

Network theory may explain the vulnerability of medieval human settlements to the Black Death pandemic.

PubMed

Gómez, José M; Verdú, Miguel

2017-03-06

Epidemics can spread across large regions becoming pandemics by flowing along transportation and social networks. Two network attributes, transitivity (when a node is connected to two other nodes that are also directly connected between them) and centrality (the number and intensity of connections with the other nodes in the network), are widely associated with the dynamics of transmission of pathogens. Here we investigate how network centrality and transitivity influence vulnerability to diseases of human populations by examining one of the most devastating pandemic in human history, the fourteenth century plague pandemic called Black Death. We found that, after controlling for the city spatial location and the disease arrival time, cities with higher values of both centrality and transitivity were more severely affected by the plague. A simulation study indicates that this association was due to central cities with high transitivity undergo more exogenous re-infections. Our study provides an easy method to identify hotspots in epidemic networks. Focusing our effort in those vulnerable nodes may save time and resources by improving our ability of controlling deadly epidemics.

Newcastle disease: current vaccine research

USDA-ARS?s Scientific Manuscript database

Newcastle disease (ND) is one of the most important infectious diseases that affect poultry due to its devastating economic impact and world-wide distribution and contribution towards malnutrition in countries that rely on production of village chickens as a source of animal protein. Besides biosec...

A porcine model of osteosarcoma

PubMed Central

Saalfrank, A; Janssen, K-P; Ravon, M; Flisikowski, K; Eser, S; Steiger, K; Flisikowska, T; Müller-Fliedner, P; Schulze, É; Brönner, C; Gnann, A; Kappe, E; Böhm, B; Schade, B; Certa, U; Saur, D; Esposito, I; Kind, A; Schnieke, A

2016-01-01

We previously produced pigs with a latent oncogenic TP53 mutation. Humans with TP53 germline mutations are predisposed to a wide spectrum of early-onset cancers, predominantly breast, brain, adrenal gland cancer, soft tissue sarcomas and osteosarcomas. Loss of p53 function has been observed in >50% of human cancers. Here we demonstrate that porcine mesenchymal stem cells (MSCs) convert to a transformed phenotype after activation of latent oncogenic TP53R167H and KRASG12D, and overexpression of MYC promotes tumorigenesis. The process mimics key molecular aspects of human sarcomagenesis. Transformed porcine MSCs exhibit genomic instability, with complex karyotypes, and develop into sarcomas on transplantation into immune-deficient mice. In pigs, heterozygous knockout of TP53 was sufficient for spontaneous osteosarcoma development in older animals, whereas homozygous TP53 knockout resulted in multiple large osteosarcomas in 7–8-month-old animals. This is the first report that engineered mutation of an endogenous tumour-suppressor gene leads to invasive cancer in pigs. Unlike in Trp53 mutant mice, osteosarcoma developed in the long bones and skull, closely recapitulating the human disease. These animals thus promise a model for juvenile osteosarcoma, a relatively uncommon but devastating disease. PMID:26974205

Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.

PubMed

Leroy, E M; Gonzalez, J-P; Baize, S

2011-07-01

Ebola and Marburg viruses are the only members of the Filoviridae family (order Mononegavirales), a group of viruses characterized by a linear, non-segmented, single-strand negative RNA genome. They are among the most virulent pathogens for humans and great apes, causing acute haemorrhagic fever and death within a matter of days. Since their discovery 50 years ago, filoviruses have caused only a few outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is negligible compared with the devastation caused by malnutrition and other infectious diseases prevalent in Africa (malaria, cholera, AIDS, dengue, tuberculosis …). Yet considerable human and financial resourses have been devoted to research on these viruses during the past two decades, partly because of their potential use as bioweapons. As a result, our understanding of the ecology, host interactions, and control of these viruses has improved considerably. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Mobile health: the power of wearables, sensors, and apps to transform clinical trials.

PubMed

Munos, Bernard; Baker, Pamela C; Bot, Brian M; Crouthamel, Michelle; de Vries, Glen; Ferguson, Ian; Hixson, John D; Malek, Linda A; Mastrototaro, John J; Misra, Veena; Ozcan, Aydogan; Sacks, Leonard; Wang, Pei

2016-07-01

Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies. © 2016 New York Academy of Sciences.

Climate change and animal diseases: making the case for adaptation.

PubMed

Cáceres, Sigfrido Burgos

2012-12-01

The exponential expansion of the human population has led to overexploitation of resources and overproduction of items that have caused a series of potentially devastating effects, including ocean acidification, ozone depletion, biodiversity loss, the spread of invasive flora and fauna and climatic changes - along with the emergence of new diseases in animals and humans. Climate change occurs as a result of imbalances between incoming and outgoing radiation in the atmosphere. This process generates heat. As concentrations of atmospheric gases reach record levels, global temperatures are expected to increase significantly. The hydrologic cycle will be altered, since warmer air can retain more moisture than cooler air. This means that some geographic areas will have more rainfall, whereas others have more drought and severe weather. The potential consequences of significant and permanent climatic changes are altered patterns of diseases in animal and human populations, including the emergence of new disease syndromes and changes in the prevalence of existing diseases. A wider geographic distribution of known vectors and the recruitment of new strains to the vector pool could result in infections spreading to more and potentially new species of hosts. If these predictions turn out to be accurate, there will be a need for policymakers to consider alternatives, such as adaptation. This review explores the linkages between climate change and animal diseases, and examines interrelated issues that arise from altered biological dynamics. Its aim is to consider various risks and vulnerabilities and to make the case for policies favoring adaptation.

N-Myristoyltransferase inhibitors as new leads to treat sleeping sickness

PubMed Central

Frearson, Julie A.; Brand, Stephen; McElroy, Stuart P.; Cleghorn, Laura A.T.; Smid, Ondrej; Stojanovski, Laste; Price, Helen P.; Guther, M. Lucia S.; Torrie, Leah S.; Robinson, David A.; Hallyburton, Irene; Mpamhanga, Chidochangu P.; Brannigan, James A.; Wilkinson, Anthony J.; Hodgkinson, Michael; Hui, Raymond; Qiu, Wei; Raimi, Olawale G.; van Aalten, Daan M. F.; Brenk, Ruth; Gilbert, Ian H.; Read, Kevin D.; Fairlamb, Alan H.; Ferguson, Michael A. J.; Smith, Deborah F.; Wyatt, Paul G.

2010-01-01

African sleeping sickness or human African trypanosomiasis (HAT), caused by Trypanosoma brucei spp., is responsible for ~30,000 deaths each year. Available treatments for this neglected disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease, when the parasite has infected the central nervous system. Here, we report the validation of a molecular target and discovery of associated lead compounds with potential to address this unmet need. Inhibition of this target, T. brucei N-myristoyltransferase (TbNMT), leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have very promising pharmaceutical properties and represent an exciting opportunity to develop oral drugs to treat this devastating disease. Our studies validate TbNMT as a promising therapeutic target for HAT. PMID:20360736

Index of Theta/Alpha Ratio of the Quantitative Electroencephalogram in Alzheimer's Disease: A Case-Control Study.

PubMed

Fahimi, Golshan; Tabatabaei, Seyed Mahmoud; Fahimi, Elnaz; Rajebi, Hamid

2017-08-01

Alzheimer's disease (AD) is a devastating neurodegenerative disorder in human beings associated with cognitive, behavioral and motor impairments. The main symptom of AD is dementia, which causes difficulties in carrying out daily practices. Brain waves are altered in people with AD. Relative indices of brain waves can be beneficial in the diagnosis of AD. In this case-control study, 50 patients with AD and 50 matched healthy individuals were enrolled in case and control groups respectively. With recording and analyzing of brain waves with the utilization of quantitative electroencephalogram (QEEG), index of theta/alpha ratio was assessed in both groups. The index of theta/alpha ratio was significantly higher in patients with AD in comparison to healthy individuals (P<0.05). Index of theta/alpha ratio obtained by QEEG provides a non-invasive diagnostic marker of AD, which may be helpful in identification of non-advanced disease in susceptible individuals.

Drosophila models of amyotrophic lateral sclerosis with defects in RNA metabolism.

PubMed

Zhang, Ke; Coyne, Alyssa N; Lloyd, Thomas E

2018-05-09

The fruit fly Drosophila Melanogaster has been widely used to study neurodegenerative diseases. The conservation of nervous system biology coupled with the rapid life cycle and powerful genetic tools in the fly have enabled the identification of novel therapeutic targets that have been validated in vertebrate model systems and human patients. A recent example is in the study of the devastating motor neuron degenerative disease amyotrophic lateral sclerosis (ALS). Mutations in genes that regulate RNA metabolism are a major cause of inherited ALS, and functional analysis of these genes in the fly nervous system has shed light on how mutations cause disease. Importantly, unbiased genetic screens have identified key pathways that contribute to ALS pathogenesis such as nucleocytoplasmic transport and stress granule assembly. In this review, we will discuss the utilization of Drosophila models of ALS with defects in RNA metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Yersinia pestis--etiologic agent of plague.

PubMed Central

Perry, R D; Fetherston, J D

1997-01-01

Plague is a widespread zoonotic disease that is caused by Yersinia pestis and has had devastating effects on the human population throughout history. Disappearance of the disease is unlikely due to the wide range of mammalian hosts and their attendant fleas. The flea/rodent life cycle of Y. pestis, a gram-negative obligate pathogen, exposes it to very different environmental conditions and has resulted in some novel traits facilitating transmission and infection. Studies characterizing virulence determinants of Y. pestis have identified novel mechanisms for overcoming host defenses. Regulatory systems controlling the expression of some of these virulence factors have proven quite complex. These areas of research have provide new insights into the host-parasite relationship. This review will update our present understanding of the history, etiology, epidemiology, clinical aspects, and public health issues of plague. PMID:8993858

How health affects small business in South Africa.

PubMed

Chao, Li-Wei; Pauly, Mark V

2007-03-01

Preventable and treatable diseases have taken a devastating human and economic toll on many developing countries. That economic toll is likely to be underestimated because most studies focus on productivity losses in the formal, or large-firm, sector; yet, a large portion of the population of developing countries works in the informal sector in very small businesses, either as an owner-worker or as an employee. It is plausible that ill health might affect small businesses most severely, possibly putting the entire business at risk. This Issue Brief summarizes a three-year study that tracks small businesses in Durban, South Africa, and investigates the connection between the owner's health and business growth, survival, or closure. The results bolster the economic case for investing resources in the prevention and treatment of disease in developing countries.

Discovery of huanglongbing (HLB) pre-symptomatic Ribonucleic acid (RNA) biomarkers

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) is the most devastating citrus disease and is associated with vector-borne Liberibacter. Currently there is no cure for huanglongbing. Visual disease symptoms appear in only a few leaves months after initial Liberibacter exposure compromising disease management by tree removal. S...

JPRS Report, West Europe

DTIC Science & Technology

1987-06-05

Economy Through 1989 (Jan Magnus Fahlstrom; DAGENS NYHETER, 9 Apr 87) 98 SOCIAL SWEDEN Lapps Weigh Emigration Following Chernobyl Devastation...after Chernobyl the Soviet state is a bogeyman for the rest of the world—in human terms, economically and in the area of envir- onmental technology...election year." 11798 , CS0: 3650/102 99 „«„■P»T SWEDEN SOCIAL LAPPS WEIGH EMIGRATION FOLLOWING CHERNOBYL DEVASTATION Stockholm DAGENS NYHETER

Beer and bread to brains and beyond: can yeast cells teach us about neurodegenerative disease?

PubMed

Gitler, Aaron D

2008-01-01

For millennia, humans have harnessed the astonishing power of yeast, producing such culinary masterpieces as bread, beer and wine. Therefore, in this new millennium, is it very farfetched to ask if we can also use yeast to unlock some of the modern day mysteries of human disease? Remarkably, these seemingly simple cells possess most of the same basic cellular machinery as the neurons in the brain. We and others have been using the baker's yeast, Saccharomyces cerevisiae, as a model system to study the mechanisms of devastating neurodegenerative diseases such as Parkinson's, Huntington's, Alzheimer's and amyotrophic lateral sclerosis. While very different in their pathophysiology, they are collectively referred to as protein-misfolding disorders because of the presence of misfolded and aggregated forms of various proteins in the brains of affected individuals. Using yeast genetics and the latest high-throughput screening technologies, we have identified some of the potential causes underpinning these disorders and discovered conserved genes that have proven effective in preventing neuron loss in animal models. Thus, these genes represent new potential drug targets. In this review, I highlight recent work investigating mechanisms of cellular toxicity in a yeast Parkinson's disease model and discuss how similar approaches are being applied to additional neurodegenerative diseases.

Bifidobacterium bifidum in a Rat Model of Necrotizing Enterocolitis: Antimicrobial Peptide and Protein Responses

PubMed Central

Underwood, Mark A.; Kananurak, Anchasa; Coursodon, Christine F.; Adkins-Reick, Camille K.; Chu, Hiutung; Bennett, Stephen H.; Wehkamp, Jan; Castillo, Patricia A.; Leonard, Brian C.; Tancredi, Daniel J.; Sherman, Michael P.; Dvorak, Bohuslav; Bevins, Charles L.

2013-01-01

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. Probiotics decrease the risk of NEC in clinical and experimental studies. Antimicrobial peptides protect the gut against noxious microbes and shape the commensal microbiota, but their role in NEC remains unclear. We report that like in human ontogeny, the rat pup has low expression of Paneth cell antimicrobials, which increases rapidly during normal development. To investigate the expression of antimicrobial peptides in experimental NEC and the impact of probiotics on their expression, premature rats were divided into three groups: dam fed (DF), hand fed with formula (FF), or hand fed with formula containing Bifidobacterium bifidum (FF+BIF). All groups were exposed to asphyxia and cold stress. The expression of lysozyme, secretory phospholipase A2, pancreatic-associated proteins 1 and 3 mRNA was elevated in the FF (NEC) group, compared to the DF and FF+BIF groups where disease was attenuated. We conclude that induction of antimicrobial peptides occurs in experimental NEC similar to that reported in human disease and is attenuated when disease is averted by probiotic B. bifidum. The induction of antimicrobial peptides is likely an adaptive mucosal response that is often not sufficient to prevent disease in the premature gut. PMID:22322385

Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus

PubMed Central

Rubins, Kathleen H.; Huggins, John W.; Fisher, Robert W.; Johnson, Anthony J.; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E.; Jahrling, Peter B.

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions. PMID:21998632

Foot-and-mouth disease virus receptors: multiple gateways to initiate infection

USDA-ARS?s Scientific Manuscript database

Since its discovery over 100 years ago as the causative agent of foot-and-mouth disease (FMD), research has been directed at understanding the biology of the foot-and-mouth disease virus (FMDV) so as to be able to control this devastating and highly contagious disease of cloven-hoofed livestock. Giv...

Pathological aspects of NDV infection in the ICPI model

USDA-ARS?s Scientific Manuscript database

Newcastle disease (ND) is caused by virulent strains of Newcastle disease virus (NDV), and is a devastating disease of poultry worldwide. The intracerebral pathogenicity index (ICPI) is the internationally recognized system used to assess the virulence of NDV strains, with those scoring = 0.7 consi...

The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer

PubMed Central

Zabron, Abigail; Edwards, Robert J.; Khan, Shahid A.

2013-01-01

Cholangiocarcinoma is a fatal cancer of the biliary epithelium and has an incidence that is increasing worldwide. Survival beyond a year of diagnosis is less than 5%, and therapeutic options are few. Known risk factors include biliary diseases such as primary sclerosing cholangitis and parasitic infestation of the biliary tree, but most cases are not associated with any of these underlying diseases. Numerous in vitro and in vivo models, as well as novel analytical techniques for human samples, are helping to delineate the many pathways implicated in this disease, albeit at a frustratingly slow pace. As yet, however, none of these studies has been translated into improved patient outcome and, overall, the pathophysiology of cholangiocarcinoma is still poorly understood. There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease. In this review, we take a bedside-to-bench approach to discussing cholangiocarcinoma and outline research opportunities for the future in this field. PMID:23520144

Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease

PubMed Central

Crompton, Peter D.; Moebius, Jacqueline; Portugal, Silvia; Waisberg, Michael; Hart, Geoffrey; Garver, Lindsey S.; Miller, Louis H.; Barillas, Carolina; Pierce, Susan K.

2014-01-01

Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease. PMID:24655294

The immune strategies of mosquito Aedes aegypti against microbial infection.

PubMed

Wang, Yan-Hong; Chang, Meng-Meng; Wang, Xue-Li; Zheng, Ai-Hua; Zou, Zhen

2018-06-01

Yellow fever mosquito Aedes aegypti transmits many devastating arthropod-borne viruses (arboviruses), such as dengue virus, yellow fever virus, Chikungunya virus, and Zika virus, which cause great concern to human health. Mosquito control is an effective method to block the spread of infectious diseases. Ae. aegypti uses its innate immune system to fight against arboviruses, parasites, and fungi. In this review, we briefly summarize the recent findings in the immune response of Ae. aegypti against arboviral and entomopathogenic infections. This review enriches our understanding of the mosquito immune system and provides evidence to support the development of novel mosquito control strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induction of antimicrobial 3-deoxyflavonoids in pome fruit trees controls fire blight.

PubMed

Halbwirth, Heidrun; Fischer, Thilo C; Roemmelt, Susanne; Spinelli, Francesco; Schlangen, Karin; Peterek, Silke; Sabatini, Emidio; Messina, Christian; Speakman, John-Bryan; Andreotti, Carlo; Rademacher, Wilhelm; Bazzi, Carlo; Costa, Guglielmo; Treutter, Dieter; Forkmann, Gert; Stich, Karl

2003-01-01

Fire blight, a devastating bacterial disease in pome fruits, causes severe economic losses worldwide. Hitherto, an effective control could only be achieved by using antibiotics, but this implies potential risks for human health, livestock and environment. A new approach allows transient inhibition of a step in the flavonoid pathway, thereby inducing the formation of a novel antimicrobial 3-deoxyflavonoid controlling fire blight in apple and pear leaves. This compound is closely related to natural phytoalexins in sorghum. The approach does not only provide a safe method to control fire blight: Resistance against different pathogens is also induced in other crop plants.

APPLICATION OF PROPICONAZOLE IN MANAGEMENT OF LAUREL WILT DISEASE IN AVOCADO (Persea americana Mill.) TREES

USDA-ARS?s Scientific Manuscript database

Laurel wilt is a vascular disease of Lauraceous plants caused by a fungus (Raffaelea spp.) that is carried by a recently introduced, nonnative ambrosia beetle (Xyleborus glabratus). The disease is devastating to Persea species including redbay (Persea borbonia) and avocado (Persea americana) trees i...

Overexpression of a citrus NDR1 ortholog increases disease resistance in Arabidopsis

USDA-ARS?s Scientific Manuscript database

Emerging devastating diseases, such as Huanglongbing (HLB) and citrus canker, have caused tremendous losses to the citrus industry worldwide. Genetic engineering is a powerful approach that could allow us to increase citrus resistance against these diseases. The key to the success of this approach r...

Breeding for cotton leaf curl disease (CLCuD) resistance

USDA-ARS?s Scientific Manuscript database

Cotton leaf curl disease (CLCuD) is caused by a whitefly (Bemisia tabaci) transmitted geminivirus. It is a major disease of cotton in Africa and South Asia, and has spread to other countries through ornamental plants. It can potentially devastate U.S. cotton where commercial varieties have no resi...

Climate Change and Health: A Position Paper of the American College of Physicians.

PubMed

Crowley, Ryan A

2016-05-03

Climate change could have a devastating effect on human and environmental health. Potential effects of climate change on human health include higher rates of respiratory and heat-related illness, increased prevalence of vector-borne and waterborne diseases, food and water insecurity, and malnutrition. Persons who are elderly, sick, or poor are especially vulnerable to these potential consequences. Addressing climate change could have substantial benefits to human health. In this position paper, the American College of Physicians (ACP) recommends that physicians and the broader health care community throughout the world engage in environmentally sustainable practices that reduce carbon emissions; support efforts to mitigate and adapt to the effects of climate change; and educate the public, their colleagues, their community, and lawmakers about the health risks posed by climate change. Tackling climate change is an opportunity to dramatically improve human health and avert dire environmental outcomes, and ACP believes that physicians can play a role in achieving this goal.

Brain/MINDS: brain-mapping project in Japan

PubMed Central

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis.

PubMed

Bauer, Yasmina; Tedrow, John; de Bernard, Simon; Birker-Robaczewska, Magdalena; Gibson, Kevin F; Guardela, Brenda Juan; Hess, Patrick; Klenk, Axel; Lindell, Kathleen O; Poirey, Sylvie; Renault, Bérengère; Rey, Markus; Weber, Edgar; Nayler, Oliver; Kaminski, Naftali

2015-02-01

The bleomycin-induced rodent lung fibrosis model is commonly used to study mechanisms of lung fibrosis and to test potential therapeutic interventions, despite the well recognized dissimilarities to human idiopathic pulmonary fibrosis (IPF). Therefore, in this study, we sought to identify genomic commonalities between the gene expression profiles from 100 IPF lungs and 108 control lungs that were obtained from the Lung Tissue Research Consortium, and rat lungs harvested at Days 3, 7, 14, 21, 28, 42, and 56 after bleomycin instillation. Surprisingly, the highest gene expression similarity between bleomycin-treated rat and IPF lungs was observed at Day 7. At this point of maximal rat-human commonality, we identified a novel set of 12 disease-relevant translational gene markers (C6, CTHRC1, CTSE, FHL2, GAL, GREM1, LCN2, MMP7, NELL1, PCSK1, PLA2G2A, and SLC2A5) that was able to separate almost all patients with IPF from control subjects in our cohort and in two additional IPF/control cohorts (GSE10667 and GSE24206). Furthermore, in combination with diffusing capacity of carbon monoxide measurements, four members of the translational gene marker set contributed to stratify patients with IPF according to disease severity. Significantly, pirfenidone attenuated the expression change of one (CTHRC1) translational gene marker in the bleomycin-induced lung fibrosis model, in transforming growth factor-β1-treated primary human lung fibroblasts and transforming growth factor-β1-treated human epithelial A549 cells. Our results suggest that a strategy focused on rodent model-human disease commonalities may identify genes that could be used to predict the pharmacological impact of therapeutic interventions, and thus facilitate the development of novel treatments for this devastating lung disease.

A Novel Genomic Signature with Translational Significance for Human Idiopathic Pulmonary Fibrosis

PubMed Central

Tedrow, John; de Bernard, Simon; Birker-Robaczewska, Magdalena; Gibson, Kevin F.; Guardela, Brenda Juan; Hess, Patrick; Klenk, Axel; Lindell, Kathleen O.; Poirey, Sylvie; Renault, Bérengère; Rey, Markus; Weber, Edgar; Nayler, Oliver; Kaminski, Naftali

2015-01-01

The bleomycin-induced rodent lung fibrosis model is commonly used to study mechanisms of lung fibrosis and to test potential therapeutic interventions, despite the well recognized dissimilarities to human idiopathic pulmonary fibrosis (IPF). Therefore, in this study, we sought to identify genomic commonalities between the gene expression profiles from 100 IPF lungs and 108 control lungs that were obtained from the Lung Tissue Research Consortium, and rat lungs harvested at Days 3, 7, 14, 21, 28, 42, and 56 after bleomycin instillation. Surprisingly, the highest gene expression similarity between bleomycin-treated rat and IPF lungs was observed at Day 7. At this point of maximal rat–human commonality, we identified a novel set of 12 disease-relevant translational gene markers (C6, CTHRC1, CTSE, FHL2, GAL, GREM1, LCN2, MMP7, NELL1, PCSK1, PLA2G2A, and SLC2A5) that was able to separate almost all patients with IPF from control subjects in our cohort and in two additional IPF/control cohorts (GSE10667 and GSE24206). Furthermore, in combination with diffusing capacity of carbon monoxide measurements, four members of the translational gene marker set contributed to stratify patients with IPF according to disease severity. Significantly, pirfenidone attenuated the expression change of one (CTHRC1) translational gene marker in the bleomycin-induced lung fibrosis model, in transforming growth factor-β1–treated primary human lung fibroblasts and transforming growth factor-β1–treated human epithelial A549 cells. Our results suggest that a strategy focused on rodent model–human disease commonalities may identify genes that could be used to predict the pharmacological impact of therapeutic interventions, and thus facilitate the development of novel treatments for this devastating lung disease. PMID:25029475

HOW to Save Dutch Elm Diseased Trees by Pruning

Treesearch

J.R. Allison; G.F. Gregory

1979-01-01

Dutch elm disease (DED), caused by the fungus, Ceratocystis ulmi, is the most devastating shade tree disease in the United States. Healthy elms can become diseased by 1) elm bark beetles that carry the fungus from elm to elm, or 2) through root grafting with already infected trees. Along with wilt symptoms, streaking (sapwood discoloration), a characteristic internal...

Derivation of chicken induced pluripotent stem cells tolerant to Newcastle disease virus-induced lysis through multiple rounds of infection

USDA-ARS?s Scientific Manuscript database

Background: Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a devastating disease of poultry and wild birds. ND is prevented by rigorous biocontainment and vaccination. One potential approach to prevent spread of the virus is production of birds that show innate resistance to NDV...

Epigenetics, microbiota, and intraocular inflammation: New paradigms of immune regulation in the eye.

PubMed

Wen, Xiaofeng; Hu, Xiao; Miao, Li; Ge, Xiaofei; Deng, Yuhua; Bible, Paul W; Wei, Lai

2018-05-01

Sight threatening immune responses that damage the eye characterize intraocular inflammatory diseases. These diseases including uveitis and age-related macular degeneration are worryingly common and quality of life shattering. Genetic studies in past decades significantly advanced our understanding of the etiology of these devastating diseases. Unfortunately, patient genetics alone failed to adequately explain disease origin, susceptibility, and progression. Non-genetic factors such as the epigenetic regulation of ocular diseases and the environmental factors triggering intraocular inflammation offer new insight into intraocular inflammatory disorders. Importantly, mounting evidence is signaling that dysbiosis of human microbiota leads to rapid epigenomic reprograming of host cells and results in the onset of many diseases. In this review, we discuss how epigenetic mechanisms and microbiota may cooperate to initiate and perpetuate ocular inflammation. Lastly, we propose that the discovery of intraocular microbiota presents a significant shift in thought affecting current approaches to the diagnosis, treatment, and prevention of intraocular inflammatory diseases such as uveitis and age-related macular degeneration. The geographical and genetic background difference in both disease presentation and genetic association of intraocular inflammatory diseases may be due to the variation of intraocular microbiota. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ten years of a multidisciplinary diabetic foot team approach in Sao Paulo, Brazil

PubMed Central

Batista, Fábio; Augusto Magalhães, Antonio; Gamba, Mônica; Nery, Caio; Cardoso, Cristina

2010-01-01

Diabetes mellitus can cause devastating foot problems including loss of protective sensation with subsequent ulcerations and amputations. The natural history and pathophysiology of diabetic foot ulcers is best understood and managed by a multiprofessional team approach. The main factors for prevention and treatment of these devastating diabetic foot conditions are shown, with special attention to education of the patient. This approach decreases the morbidity of the disease, besides its economical and social feasibility. PMID:22396805

Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation

PubMed Central

Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M

2015-01-01

Background Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. Methods In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. Results The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. Conclusions In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. PMID:25908835

Preparedness for emerging infectious diseases: pathways from anticipation to action.

PubMed

Brookes, V J; Hernández-Jover, M; Black, P F; Ward, M P

2015-07-01

Emerging and re-emerging infectious disease (EID) events can have devastating human, animal and environmental health impacts. The emergence of EIDs has been associated with interconnected economic, social and environmental changes. Understanding these changes is crucial for EID preparedness and subsequent prevention and control of EID events. The aim of this review is to describe tools currently available for identification, prioritization and investigation of EIDs impacting human and animal health, and how these might be integrated into a systematic approach for directing EID preparedness. Environmental scanning, foresight programmes, horizon scanning and surveillance are used to collect and assess information for rapidly responding to EIDs and to anticipate drivers of emergence for mitigating future EID impacts. Prioritization of EIDs - using transparent and repeatable methods - based on disease impacts and the importance of those impacts to decision-makers can then be used for more efficient resource allocation for prevention and control. Risk assessment and simulation modelling methods assess the likelihood of EIDs occurring, define impact and identify mitigation strategies. Each of these tools has a role to play individually; however, we propose integration of these tools into a framework that enhances the development of tactical and strategic plans for emerging risk preparedness.

A role for ion channels in perivascular glioma invasion

PubMed Central

Thompson, Emily G.

2017-01-01

Malignant gliomas are devastating tumors, frequently killing those diagnosed in little over a year. The profuse infiltration of glioma cells into healthy tissue surrounding the main tumor mass is one of the major obstacles limiting the improvement of patient survival. Migration along the abluminal side of blood vessels is one of the salient features of glioma cell invasion. Invading glioma cells are attracted to the vascular network, in part by the neuro-peptide bradykinin, where glioma cells actively modify the gliovascular interface and undergo volumetric alterations to navigate the confined space. Critical to these volume modifications is a proposed hydrodynamic model that involves the flux of ions in and out of the cell, followed by osmotically obligated water. Ion and water channels expressed by the glioma cell are essential in this model of invasion and make opportune therapeutic targets. Lastly, there is growing evidence that vascular-associated glioma cells are able to control the vascular tone, presumably to free up space for invasion and growth. The unique mechanisms that enable perivascular glioma invasion may offer critical targets for therapeutic intervention in this devastating disease. Indeed, a chloride channel-blocking peptide has already been successfully tested in human clinical trials. PMID:27424110

The lyme disease pathogen has no effect on the survival of its rodent reservoir host.

PubMed

Voordouw, Maarten J; Lachish, Shelly; Dolan, Marc C

2015-01-01

Zoonotic pathogens that cause devastating morbidity and mortality in humans may be relatively harmless in their natural reservoir hosts. The tick-borne bacterium Borrelia burgdorferi causes Lyme disease in humans but few studies have investigated whether this pathogen reduces the fitness of its reservoir hosts under natural conditions. We analyzed four years of capture-mark-recapture (CMR) data on a population of white-footed mice, Peromyscus leucopus, to test whether B. burgdorferi and its tick vector affect the survival of this important reservoir host. We used a multi-state CMR approach to model mouse survival and mouse infection rates as a function of a variety of ecologically relevant explanatory factors. We found no effect of B. burgdorferi infection or tick burden on the survival of P. leucopus. Our estimates of the probability of infection varied by an order of magnitude (0.051 to 0.535) and were consistent with our understanding of Lyme disease in the Northeastern United States. B. burgdorferi establishes a chronic avirulent infection in their rodent reservoir hosts because this pathogen depends on rodent mobility to achieve transmission to its sedentary tick vector. The estimates of B. burgdorferi infection risk will facilitate future theoretical studies on the epidemiology of Lyme disease.

PET Scans Obtained for Evaluation of Cognitive Dysfunction

PubMed Central

Silverman, Daniel H. S.; Mosconi, Lisa; Ercoli, Linda; Chen, W; Small, Gary W.

2015-01-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism with devastating neuropathologic, economic, social and clinical consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are carried out with [18F]fluorodeoxyglucose (FDG) as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility in evaluating patients with cognitive impairment, and in distinguishing among primary neurodegenerative disorders and other etiologies for cognitive decline. In addition to focusing upon the effects on cerebral metabolism examined with FDG PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact upon the enormous human toll exacted by these diseases. PMID:18514081

Positron emission tomography scans obtained for the evaluation of cognitive dysfunction.

PubMed

Silverman, Daniel H S; Mosconi, Lisa; Ercoli, Linda; Chen, Wei; Small, Gary W

2008-07-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism, with devastating neuropathologic, clinical, social, and economic consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are performed with (18)F-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility for clinicians evaluating patients with cognitive impairment and in distinguishing among primary neurodegenerative disorders and other etiologies contributing to cognitive decline. In addition to focusing on the effects on cerebral metabolism examined with (18)F-fluorodeoxyglucose PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact on the enormous human toll exacted by these diseases.

A comparative study of three detection techniques for Leifsonia xyli subsp. xyli, the causal pathogen of sugarcane ratoon stunting disease

USDA-ARS?s Scientific Manuscript database

Ratoon stunting disease (RSD), which is caused by the bacterium Leifsonia xyli subsp. xyli (Lxx), is now recognized worldwide as the most economically devastating disease impacting sugarcane. RSD causes significant yield losses and variety degradation. Diagnosis of RSD is challenging because it does...

Constitutively active IRF7/IRF3 fusion protein completely protects swine against Foot-and-Mouth Disease

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) remains one of the most devastating livestock diseases around the world. Several serotype specific vaccine formulations exist but require about 5-7 days to induce protective immunity. Our previous studies have shown that a constitutively active fusion protein of porcine ...

Proteomics analysis reveals novel host molecular mechanisms associated with thermotherapy of ‘Ca. Liberibacter asiaticus’-infected citrus plants

USDA-ARS?s Scientific Manuscript database

Citrus huanglongbing (HLB) is the most devastating disease of citrus plants, and longer-term measures for controlling the disease via breeding or genetic engineering are hampered by the fact that all cultivated citrus species are susceptible to the disease. However, the degree of HLB susceptibility ...

Ascochyta blight of chickpeas

USDA-ARS?s Scientific Manuscript database

Chickpea is becoming increasingly important as a rotational crop in cereal production systems. Ascochyta blight is the most devastating disease of chickpea and must be appropriately managed to minimize its damage to crops and increase chickpea yield. The disease is caused by the fungus Ascochyta r...

Unifying mechanism for different fibrotic diseases

PubMed Central

Wernig, Gerlinde; Chen, Shih-Yu; Cui, Lu; Van Neste, Camille; Tsai, Jonathan M.; Kambham, Neeraja; Vogel, Hannes; Natkunam, Yaso; Gilliland, D. Gary; Nolan, Garry; Weissman, Irving L.

2017-01-01

Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts. Expression of the related AP1 transcription factor FRA2 was restricted to pulmonary artery hypertension. Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple organs and steatohepatosis, which was dependent on sustained c-Jun expression. Single cell mass cytometry revealed that c-Jun activates multiple signaling pathways in mice, including pAkt and CD47, which were also induced in human disease. αCD47 antibody treatment and VEGF or PI3K inhibition reversed various organ c-Jun–mediated fibroses in vivo. These data suggest that c-JUN is a central molecular mediator of most fibrotic conditions. PMID:28424250

Returning to Humanity's Moral Heritages

ERIC Educational Resources Information Center

Narvaez, Darcia

2016-01-01

The main arguments of my lecture were how humans are failing themselves and devastating earth's biosphere, at least in part, because they became uncooperative with two key ecological inheritances: raising the young within the human evolved developmental niche and, as part of this, facilitating the development of a deep attachment to, knowledge of…

Transgenic expression of antimicrobial peptide D2A21 confers resistance to diseases incited by Pseudomonas syringae pv. tabaci and Xanthomonas citri, but not Candidatus Liberibacter asiaticus

USDA-ARS?s Scientific Manuscript database

Citrus Huanglongbing (HLB) associated with ‘Candidatus Liberibacter asiaticus’ (Las) and citrus canker disease incited by Xanthomonas citri are the most devastating citrus diseases worldwide. To control citrus HLB and canker disease, we previously screened over forty antimicrobial peptides (AMPs) in...

COMPARATIVE GENOME ANALYSES OF MONILIOPHTHORA PERNICIOSA AND MONILIOPHTHORA RORERI: TWO CLOSELY RELATED PHYTOPATHOGENIC BASIDIOMYCETES THAT CAUSE DISTINCTLY DIFFERENT DISEASES OF THEOBROMA CACAO

USDA-ARS?s Scientific Manuscript database

Theobroma cacao (cacao), the source of chocolate, is a tropical understory tree. Fungal diseases such as Witches’ Broom Disease (WBD) and Frosty Pod Rot Disease (FPRD) of cacao have devastated cacao production in much of the Western Hemisphere and are threats to the main cacao producing regions in A...

Effect of foot-and-mouth disease virus infection on the frequency, phenotype and function of circulating dendritic cells in cattle

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms in FMDV-infected animals appear within 2 to 3 days of exposure. Dendritic cells (DC) play an essential role in protective immune responses agai...

Detection and Control of Prion Diseases in Food Animals

PubMed Central

Hedlin, Peter; Taschuk, Ryan; Potter, Andrew; Griebel, Philip; Napper, Scott

2012-01-01

Transmissible spongiform encephalopathies (TSEs), or prion diseases, represent a unique form of infectious disease based on misfolding of a self-protein (PrPC) into a pathological, infectious conformation (PrPSc). Prion diseases of food animals gained notoriety during the bovine spongiform encephalopathy (BSE) outbreak of the 1980s. In particular, disease transmission to humans, to the generation of a fatal, untreatable disease, elevated the perspective on livestock prion diseases from food production to food safety. While the immediate threat posed by BSE has been successfully addressed through surveillance and improved management practices, another prion disease is rapidly spreading. Chronic wasting disease (CWD), a prion disease of cervids, has been confirmed in wild and captive populations with devastating impact on the farmed cervid industries. Furthermore, the unabated spread of this disease through wild populations threatens a natural resource that is a source of considerable economic benefit and national pride. In a worst-case scenario, CWD may represent a zoonotic threat either through direct transmission via consumption of infected cervids or through a secondary food animal, such as cattle. This has energized efforts to understand prion diseases as well as to develop tools for disease detection, prevention, and management. Progress in each of these areas is discussed. PMID:23738120

Early detection of HLB with metabolomics

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) is the most devastating of all citrus diseases and poses a serious threat to the U.S. citrus industry. Candidatus Liberibacter asiaticus (CLas) is a bacterium associated with, and believed to cause, HLB disease of citrus. Confirmation of CLas infection is crucial for regulatory a...

Predictors of Meningococcal Vaccination among University Students

ERIC Educational Resources Information Center

D'Heilly, Sarah; Ehlinger, Edward; Nichol, Kristin

2006-01-01

Invasive disease secondary to Neisseria meningitidis is a rare but devastating illness among university students. The Advisory Committee on Immunization Practices recommends educating college freshmen about meningococcal disease and vaccinating all college freshmen who live in residence halls. We conducted this survey to gain a better…

Three American tragedies: chestnut blight, butternut canker, and Dutch elm disease

Treesearch

Scott E. Schlarbaum; Frederick Hebard; Pauline C. Spaine; Joseph C. Kamalay

1998-01-01

Three North American tree species, American chestnut (Castanea dentata), butternut (Juglans cinerea), and American elm (Ulmus americana), have been devastated by exotic fungal diseases over the last century. American chestnut was eliminated from eastern forests as a dominant species by chestnut blight (...

Quantitative disease resistance: dissection and adoption in maize

USDA-ARS?s Scientific Manuscript database

Maize is the world’s most widely cultivated crop, providing food, feed, and biofuel. Maize production is constantly threatened by the presence of devastating pathogens worldwide. Characterization of the genetic components underlying disease resistance is a major research area in maize which is highl...

Introduction to Oomycetes

USDA-ARS?s Scientific Manuscript database

The oomycetes, also known as “water molds”, are a group of several hundred organisms that include some of the most devastating plant pathogens. The diseases they cause include seedling blights, damping-off, root rots, foliar blights and downy mildews. Some notable diseases are the late blight of po...

The SH-SY5Y cell line in Parkinson's disease research: a systematic review.

PubMed

Xicoy, Helena; Wieringa, Bé; Martens, Gerard J M

2017-01-24

Parkinson's disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, improvement of our current understanding of the molecular and cellular mechanisms underlying PD pathogenesis and progression is crucial. For this purpose, standardization of research protocols and disease models is necessary. As human dopaminergic neurons, the cells mainly affected in PD, are difficult to obtain and maintain as primary cells, current PD research is mostly performed with permanently established neuronal cell models, in particular the neuroblastoma SH-SY5Y lineage. This cell line is frequently chosen because of its human origin, catecholaminergic (though not strictly dopaminergic) neuronal properties, and ease of maintenance. However, there is no consensus on many fundamental aspects that are associated with its use, such as the effects of culture media composition and of variations in differentiation protocols. Here we present the outcome of a systematic review of scientific articles that have used SH-SY5Y cells to explore PD. We describe the cell source, culture conditions, differentiation protocols, methods/approaches used to mimic PD and the preclinical validation of the SH-SY5Y findings by employing alternative cellular and animal models. Thus, this overview may help to standardize the use of the SH-SY5Y cell line in PD research and serve as a future user's guide.

Towards a global initiative for fibrosis treatment (GIFT)

PubMed Central

Agusti, Alvar; Crestani, Bruno; Schwartz, David A.; Chambers, Rachel C.; Maher, Toby M.; Faner, Rosa; Mora, Ana Lucia; Rojas, Mauricio; Antoniou, Katerina M.; Sellares, Jacobo

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterised by increased scarring of lung tissue. Despite the recent introduction of novel drugs that slow disease progression, IPF remains a deadly disease, and the benefits of these new drugs differ markedly between patients. Human diseases arise due to alterations in an almost limitless network of interconnected genes, proteins, metabolites, cells and tissues, in direct relationship with a continuously changing macro- or microenvironment. Systems biology is a novel research strategy that seeks to understand the structure and behaviour of the so-called “emergent properties” of complex systems, such as those involved in disease pathogenesis, which are most often overlooked when just one element of disease pathogenesis is observed in isolation. This article summarises the debate that took place during a European Respiratory Society research seminar in Barcelona, Spain on December 15–16, 2016, which focused on how systems biology could generate new data by integrating the different IPF pathogenic levels of complexity. The main conclusion of the seminar was to create a global initiative to improve IPF outcomes by integrating cutting-edge international research that leverages systems biology to develop a precision medicine approach to tackle this devastating disease. PMID:29214157

[Experience of Handicap International in providing humanitarian relief in region near Aceh, Indonesia from March 1 to 27, 2005].

PubMed

Gillet, Y

2005-01-01

This report describes the experience of the author in March 2005 during the relief efforts deployed in the region near Aceh, Indonesia (North Sumatra) by Handicap International, one of the 400 NGO that provided humanitarian aid following the tsunami disaster that struck Southeast Asia on December 26, 2004. Working in Banda Aceh and Meulaboh, the author was confronted with the extent of the devastation both in terms of property damage and human suffering. Clinical cases were often severe and rarely encountered in industrialized countries. The tsunami worsened the already poor sanitary conditions: rundown care facilities, poorly trained health care personnel, tropical disease, poor hygiene, and AVP.

ATP Synthase Diseases of Mitochondrial Genetic Origin

PubMed Central

Dautant, Alain; Meier, Thomas; Hahn, Alexander; Tribouillard-Tanvier, Déborah; di Rago, Jean-Paul; Kucharczyk, Roza

2018-01-01

Devastating human neuromuscular disorders have been associated to defects in the ATP synthase. This enzyme is found in the inner mitochondrial membrane and catalyzes the last step in oxidative phosphorylation, which provides aerobic eukaryotes with ATP. With the advent of structures of complete ATP synthases, and the availability of genetically approachable systems such as the yeast Saccharomyces cerevisiae, we can begin to understand these molecular machines and their associated defects at the molecular level. In this review, we describe what is known about the clinical syndromes induced by 58 different mutations found in the mitochondrial genes encoding membrane subunits 8 and a of ATP synthase, and evaluate their functional consequences with respect to recently described cryo-EM structures. PMID:29670542

Transcriptomics reveals multiple resistance mechanisms against cotton leaf curl disease in a naturally immune cotton species, Gossypium arboreum

USDA-ARS?s Scientific Manuscript database

Cotton is an economically important crop affected by a number of abiotic and biotic stresses. Cotton leaf curl disease (CLCuD) is caused by virus in the genus Begomovirus (family Geminiviridae), collectively called cotton leaf curl viruses (CLCuVs). It is one of the most devastating virual diseases ...

The Lolium pathotype of Magnaporthe oryzae recovered from a single blasted wheat plant in the United States

USDA-ARS?s Scientific Manuscript database

Wheat blast is a devastating disease that was first identified in Brazil and has subsequently spread to surrounding countries in South America. In May 2011, disease scouting in a University of Kentucky wheat trial plot in Princeton, Kentucky identified a single plant with disease symptoms that diffe...

Potential Linkage Between Cerebrovascular Diseases and Metabolic Syndrome.

PubMed

Jabir, Nasimudeen R; Firoz, Chelapram Kandy; Khan, Mohd Shahnawaz; Zaidi, Syed Kashif; Ashraf, Ghulam Md; Shakil, Shazi; Kamal, Mohammad Amjad; Tabrez, Shams

2017-01-01

Cerebrovascular disease (CD) and metabolic syndrome (MetS) are two devastating health dilemma that continues to be a potential contributor to disability and mortality in human population all across the world. Scientific data clearly shows several mechanistic similarities between these two co-existing and interlinked conditions. The linkage exacerbates ongoing patho-physiological condition towards more lethal events. In view of the presence of modifiable risk factors in both CD and MetS, their management holds potential therapeutic value. Hence, developing common treatment strategies for these diseases could involve common molecular agents. In this communication, we have summarized some of the common pathological conditions viz. abdominal obesity, insulin resistance, dyslipidemia, hypertension, and endothelial dysfunction that further deteriorate existing homeostasis in CD and MetS. Based on our article, it is advocated that substantial improvements in novel multi-targeted drug discovery could provide the effective treatment methods in order to avoid the fatal complications related with CD and MetS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Research on Dynamic Monitoring (1990-2010)of Schistosomiasis Vector- Snail at Xinmin Beach, Gaoyou Lake, Jiangsu Province, China

NASA Astrophysics Data System (ADS)

Liu, Zhaoyan; Li, Chuanrong; Tang, Lingli; Zhou, Xiaonong; Ma, Lingling

2014-11-01

Schistosomiasis is a parasitic disease that menaces human health. In terms of impact, this disease is second only to malaria as the most devastating parasitic disease. Oncomelania hupensis (snail) is the unique intermediate host of schistosoma, so monitoring and controlling of the number of snail is key to reduce the risk of schistosomiasis transmission. Remote sensing technology can real-timely access the large-scale environmental factors related to snail breeding and reproduction, and can also provide the efficient information to determine the location, area, and spread tendency of snail. Based on the T-S (Takagi-Sugeno) fuzzy information theory, a quantitative remote sensing monitoring model of snail has been developed in previous wok. In a case study, this paper will take Xinmin beach, Gaoyou Lake as new research area, carry out 20 years (1990 - 2010) dynamic monitoring, to further validate the effectiveness of the T-S Fuzzy RS snail monitoring model.

Research on Dynamic Monitoring (1990-2010) of Schistosomiasis Vector-Snail at Xinmin Beach, Gaoyou Lake, Jiangsu Province, China

NASA Astrophysics Data System (ADS)

Liu, Zhaoyan; Li, Chuanrong; Tang, Lingli; Zhou, Xiaonong; Ma, Lingling

2014-11-01

Schistosomiasis is a parasitic disease that menaces human health. In terms of impact, this disease is second only to malaria as the most devastating parasitic disease. Oncomelania hupensis (snail) is the unique intermediate host of schistosoma, so monitoring and controlling of the number of snail is key to reduce the risk of schistosomiasis transmission. Remote sensing technology can real-timely access the large-scale environmental factors related to snail breeding and reproduction, and can also provide the efficient information to determine the location, area, and spread tendency of snail. Based on the T-S (Takagi-Sugeno) fuzzy information theory, a quantitative remote sensing monitoring model of snail has been developed in previous wok. In a case study, this paper will take Xinmin beach, Gaoyou Lake as new research area, carry out 20 years (1990 - 2010) dynamic monitoring, to further validate the effectiveness of the T-S Fuzzy RS snail monitoring model.

II. Pathogens

Treesearch

Ned B. Klopfenstein; Brian W. Geils

2011-01-01

Invasive fungal pathogens have caused immeasurably large ecological and economic damage to forests. It is well known that invasive fungal pathogens can cause devastating forest diseases (e.g., white pine blister rust, chestnut blight, Dutch elm disease, dogwood anthracnose, butternut canker, Scleroderris canker of pines, sudden oak death, pine pitch canker) (Maloy 1997...

Spatiotemporal patterns in the airborne dispersal of spinach downy mildew

USDA-ARS?s Scientific Manuscript database

Downy mildew, caused by the biotrophic oomycete pathogen, Peronospora effusa, is the most devastating disease of spinach that threatens sustainable production. The disease results in yellow lesions that render leaves unmarketable as the high value fresh produce. In this study, the levels of D...

The Draft Genome Sequence of Mycosphaerella fijiensis, the Black Sigatoka Pathogen of Banana

USDA-ARS?s Scientific Manuscript database

Mycosphaerella fijiensis is a fungal pathogen of banana and the causal agent of the devastating Black Sigatoka or black leaf streak disease. Its control requires weekly fungicide applications when bananas are grown under disease-conducive conditions, which mostly represent precarious tropical enviro...

The phloem-sap feeding mealybug (Ferrisia virgata) carries 'Candidatus Liberibacter asiaticus' populations without transmitting disease

USDA-ARS?s Scientific Manuscript database

Candidatus Liberibacter asiaticus (Las) is the primary causal agent of huanglongbing (HLB), the most devastating disease of citrus worldwide. Currently the known insect vectors of the HLB-associated bacteria are three species of psyllids, Diaphorina citri (Hemiptera: Sternorrhyncha: Psyllidae), Trio...

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

PubMed

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, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

Human prion diseases: surgical lessons learned from iatrogenic prion transmission

PubMed Central

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

2016-01-01

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, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments. PMID:27364252

Second impact syndrome in football: new imaging and insights into a rare and devastating condition.

PubMed

Weinstein, Elizabeth; Turner, Michael; Kuzma, Benjamin B; Feuer, Henry

2013-03-01

Premature return to play for the concussed pediatric athlete may result in devastating neurological injury. Identification of at-risk patients and ideal management of the concussed athlete remain challenging for the pediatrician. The authors review a case of second impact syndrome in which neuroimaging was obtained between the first and second impacts, a circumstance which to their knowledge has not been previously reported. This case offers new insights into the underlying pathophysiology of this disease process and potential risk factors for its development.

Novel Molecular Therapies for Heritable Skin Disorders

PubMed Central

Uitto, Jouni; Christiano, Angela M.; Irwin McLean, W. H.; McGrath, John A.

2013-01-01

Tremendous progress has been made in the past two decades in molecular genetics of heritable skin diseases, and pathogenic mutations have been identified in as many as 500 distinct human genes. This progress has resulted in improved diagnosis with prognostic implications, refined genetic counseling, and has formed the basis for prenatal and presymptomatic testing as well as preimplantation genetic diagnosis. However, there has been relatively little progress in developing effective and specific treatments for these often devastating diseases. Very recently, however, a number of novel molecular strategies, including gene therapy, cell-based approaches, and protein replacement therapy have been explored for treatment of these conditions. This overview will focus on the prototypic heritable blistering disorders, epidermolysis bullosa and related keratinopathies, in which significant progress has been recently made towards treatment, and illustrate how some of the translational research therapies have already entered the clinical arena. PMID:22158553

Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis.

PubMed

Dagenais, Taylor R T; Keller, Nancy P

2009-07-01

Aspergillus species are globally ubiquitous saprophytes found in a variety of ecological niches. Almost 200 species of aspergilli have been identified, less than 20 of which are known to cause human disease. Among them, Aspergillus fumigatus is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis (IA) in the immunocompromised patient population. IA is a devastating illness, with mortality rates in some patient groups reaching as high as 90%. Studies identifying and assessing the roles of specific factors of A. fumigatus that contribute to the pathogenesis of IA have traditionally focused on single-gene deletion and mutant characterization. In combination with recent large-scale approaches analyzing global fungal responses to distinct environmental or host conditions, these studies have identified many factors that contribute to the overall pathogenic potential of A. fumigatus. Here, we provide an overview of the significant findings regarding A. fumigatus pathogenesis as it pertains to invasive disease.

Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies

PubMed Central

Smits, Paulien; Smeitink, Jan; van den Heuvel, Lambert

2010-01-01

Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders. PMID:20396601

The Geomyces fungi: ecology and distribution

USGS Publications Warehouse

Hayes, Mark A.

2012-01-01

White-nose syndrome (WNS) is a devastating disease affecting hibernating bats, first documented in winter 2006 in eastern North America. Over 5.5 million bats of several species may have died as a result of this disease. The fungus Geomyces destructans is now considered the causal agent of WNS, and this species may have been recently introduced into North American bat hibernation habitats. This overview summarizes the ecology and distribution of Geomyces fungi. Species in this genus are common in the soils of temperate and high-latitude ecosystems and are capable of withstanding and thriving in cold, low-nutrient polar environments. These species are dispersed by wind, groundwater, arthropods, birds, and mammals and are carried by humans, their clothing, and their equipment. These characteristics present significant challenges to biologists, managers, and others charged with controlling the spread of WNS and G. destructans in other parts of North America and the biosphere.

The disease of corruption: views on how to fight corruption to advance 21st century global health goals.

PubMed

Mackey, Tim K; Kohler, Jillian Clare; Savedoff, William D; Vogl, Frank; Lewis, Maureen; Sale, James; Michaud, Joshua; Vian, Taryn

2016-09-29

Corruption has been described as a disease. When corruption infiltrates global health, it can be particularly devastating, threatening hard gained improvements in human and economic development, international security, and population health. Yet, the multifaceted and complex nature of global health corruption makes it extremely difficult to tackle, despite its enormous costs, which have been estimated in the billions of dollars. In this forum article, we asked anti-corruption experts to identify key priority areas that urgently need global attention in order to advance the fight against global health corruption. The views shared by this multidisciplinary group of contributors reveal several fundamental challenges and allow us to explore potential solutions to address the unique risks posed by health-related corruption. Collectively, these perspectives also provide a roadmap that can be used in support of global health anti-corruption efforts in the post-2015 development agenda.

Herpes simplex virus-mediated human hypoxanthine-guanine phosphoribosyltransferase gene transfer into neuronal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palella, T.D.; Silverman, L.J.; Schroll, C.T.

1988-01-01

The virtually complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a devastating neurological disease, Lesch-Nyhan syndrome. Transfer of the HPRT gene into fibroblasts and lymphoblasts in vitro and into hematopoietic cells in vivo has been accomplished by other groups with retroviral-derived vectors. It appears to be necessary, however, to transfer the HPRT gene into neuronal cells to correct the neurological dysfunction of this disorder. The neurotropic virus herpes simplex virus type 1 has features that make it suitable for use as a vector to transfer the HPRT gene into neuronal tissue. This report describes the isolationmore » of an HPRT-deficient rat neuroma cell line, designated B103-4C, and the construction of a recombinant herpes simplex virus type 1 that contained human HPRT cDNA. These recombinant viruses were used to infect B103-4C cells. Infected cells expressed HPRT activity which was human in origin.« less

Citrus Genomics

PubMed Central

Talon, Manuel; Gmitter Jr., Fred G.

2008-01-01

Citrus is one of the most widespread fruit crops globally, with great economic and health value. It is among the most difficult plants to improve through traditional breeding approaches. Currently, there is risk of devastation by diseases threatening to limit production and future availability to the human population. As technologies rapidly advance in genomic science, they are quickly adapted to address the biological challenges of the citrus plant system and the world's industries. The historical developments of linkage mapping, markers and breeding, EST projects, physical mapping, an international citrus genome sequencing project, and critical functional analysis are described. Despite the challenges of working with citrus, there has been substantial progress. Citrus researchers engaged in international collaborations provide optimism about future productivity and contributions to the benefit of citrus industries worldwide and to the human population who can rely on future widespread availability of this health-promoting and aesthetically pleasing fruit crop. PMID:18509486

Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yihua; Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031; Fang, Rong

2010-05-28

Lung cancer is one of the most devastating diseases worldwide. RGS17 is previously shown to be over-expressed in human lung adenocarcinomas and plays an important role in lung tumor growth. Here we have identified a miRNA, has-mir-182, involved in the regulation of RGS17 expression through two conserved sites located in its 3' UTR region. Consistently, endogenous RGS17 expression level is regulated by hsa-mir-182 in human lung cancer cell lines. Similar to the knockdown of RGS17, ectopic expression of hsa-mir-182 significantly inhibits lung cancer cell proliferation and anchorage-independent cell growth, which can be rescued by re-expression of RGS17. Taken together, thesemore » data have provided the first evidence of miRNA regulation of RGS17 expression in lung cancer.« less

Preventing the return of smallpox: molecular modeling studies on thymidylate kinase from Variola virus.

PubMed

Guimarães, Ana Paula; Ramalho, Teodorico Castro; França, Tanos Celmar Costa

2014-01-01

Smallpox was one of the most devastating diseases in the human history and still represents a serious menace today due to its potential use by bioterrorists. Considering this threat and the non-existence of effective chemotherapy, we propose the enzyme thymidylate kinase from Variola virus (VarTMPK) as a potential target to the drug design against smallpox. We first built a homology model for VarTMPK and performed molecular docking studies on it in order to investigate the interactions with inhibitors of Vaccinia virus TMPK (VacTMPK). Subsequently, molecular dynamics (MD) simulations of these compounds inside VarTMPK and human TMPK (HssTMPK) were carried out in order to select the most promising and selective compounds as leads for the design of potential VarTMPK inhibitors. Results of the docking and MD simulations corroborated to each other, suggesting selectivity towards VarTMPK and, also, a good correlation with the experimental data.

Protein kinase A and fungal virulence: a sinister side to a conserved nutrient sensing pathway.

PubMed

Fuller, Kevin K; Rhodes, Judith C

2012-01-01

Diverse fungal species are the cause of devastating agricultural and human diseases. As successful pathogenesis is dependent upon the ability of the fungus to adapt to the nutritional and chemical environment of the host, the understanding of signaling pathways required for such adaptation will provide insights into the virulence of these pathogens and the potential identification of novel targets for antifungal intervention. The cAMP-PKA signaling pathway is well conserved across eukaryotes. In the nonpathogenic yeast, S. cerevisiae, PKA is activated in response to extracellular nutrients and subsequently regulates metabolism and growth. Importantly, this pathway is also a regulator of pathogenesis, as defects in PKA signaling lead to an attenuation of virulence in diverse plant and human pathogenic fungi. This review will compare and contrast PKA signaling in S. cerevisiae vs. various pathogenic species and provide a framework for the role of this pathway in regulating fungal virulence.

Machine Learning for Characterization of Insect Vector Feeding

PubMed Central

Willett, Nora S.; Stelinski, Lukasz L.; Lapointe, Stephen L.

2016-01-01

Insects that feed by ingesting plant and animal fluids cause devastating damage to humans, livestock, and agriculture worldwide, primarily by transmitting pathogens of plants and animals. The feeding processes required for successful pathogen transmission by sucking insects can be recorded by monitoring voltage changes across an insect-food source feeding circuit. The output from such monitoring has traditionally been examined manually, a slow and onerous process. We taught a computer program to automatically classify previously described insect feeding patterns involved in transmission of the pathogen causing citrus greening disease. We also show how such analysis contributes to discovery of previously unrecognized feeding states and can be used to characterize plant resistance mechanisms. This advance greatly reduces the time and effort required to analyze insect feeding, and should facilitate developing, screening, and testing of novel intervention strategies to disrupt pathogen transmission affecting agriculture, livestock and human health. PMID:27832081

Grapevines undergo varying shifts in secondary metabolic profiles when infected with Xylella fastidiosa

USDA-ARS?s Scientific Manuscript database

Pierce’s disease (PD) is a devastating disease of grapevine caused by the bacterial pathogen Xylella fastidiosa (Xf). Key to the development and optimization of PD-tolerant grape cultivars is improved understanding about how grapevines defend themselves against Xf. This study complements histologica...

Identification of novel powdery mildew resistance sources in wheat

USDA-ARS?s Scientific Manuscript database

Powdery mildew is a globally dominating disease of wheat with a high occurrence frequency, and genetic resistance plays an important role in managing this devastating disease. The objectives of this study were to evaluate leaf rust resistance and the underlying genes of breeding lines in the USA, a...

Understanding the molecular mechanisms of rice blast resistance using rice mutants

USDA-ARS?s Scientific Manuscript database

Induced mutation can be useful for studying resistance gene controlled plant immunity. Resulting knowledge should benefit the development of strategies for crop protection. The Pi-ta gene in rice has been effectively deployed for preventing rice blast disease-the most devastating disease of rice wo...

Label-Free Detection of Soybean Rust Spores using Photonic Crystal Biosensors

USDA-ARS?s Scientific Manuscript database

Soybean rust, caused by the fungus Phakopsora pachyrhizi, is one of the most devastating foliar diseases affecting soybeans grown worldwide. The disease was reported for the first time in the United States in 2004. Early spore detection, prior to the appearance of visible symptoms, is critical to ef...

High density mapping of a resistance gene to Ug99 from an Iranian landrace

USDA-ARS?s Scientific Manuscript database

Managing the disease wheat stem rust caused by Puccinia graminis f. sp. tritici (Pgt) including the highly virulent race TTKSK is imperative for the preservation of global food security. The most effective strategy for managing this potentially devastating disease is pyramiding several resistance ge...

Puccinia coronata f. sp. avenae: a threat to global oat production

USDA-ARS?s Scientific Manuscript database

Puccinia coronata f. sp. avenae causes crown rust disease in cultivated and wild oat. The significant yield losses inflicted by this pathogen makes crown rust the most devastating disease in the oat industry. P. coronata f. sp. avenae is a basidiomycete fungus with an obligate biotrophic lifestyle a...

FNL Scientists and Collaborators Solve 3-D Structure of Key Protein in Alzheimer’s Disease | FNLCR Staging

Cancer.gov

Researchers at the Frederick National Lab (FNL) have collaborated in solving the three-dimensional structure of a key protein in Alzheimer’s disease, providing new insight into the basic mechanisms that give rise to the devastating illness. The pro

Simultaneous laurel wilt disease biology and resistance research

Treesearch

Jason A. Smith; Randy C. Ploetz

2012-01-01

Laurel wilt (LW) is a devastating, emerging disease of native and non-native members of the Lauraceae family in the southeastern United States. Currently, the fungal pathogen (Raffaelea lauricola) and its vector (Xyleborus glabratus) are found in Alabama, Florida, Georgia, Mississippi, and North and South Carolina. The wilt is...

Mapping a new black spot resistance locus in rose [abstract

USDA-ARS?s Scientific Manuscript database

Rose black spot, caused by Diplocarpon rosae, is one of the most devastating foliar diseases of cultivated roses (Rosa hybrida). The pathogen is globally distributed and has the potential to cause large economic losses in the outdoor rose industry. Genetic resistance is the most economical disease m...

Developing a disease resistance research program for tanoaks

Treesearch

Katherine J. Hayden; Jessica W. Wright; Richard S. Dodd; Matteo Garbelotto

2012-01-01

The introduced pathogen Phtyophthora ramorum has had a devastating impact on populations of tanoak (Notholithocarpus densiflorus (Hook. & Arn.) Manos, Cannon & S.H.Oh) in California and Oregon, where it causes the disease known as sudden oak death. Tanoaks are a keystone species ecologically, and one of the few species that are...

Repellency of Selected Psidium guajava cultivars to the Asian citrus psyllid, Diaphorina citri

USDA-ARS?s Scientific Manuscript database

Asiatic huanglongbing (HLB)(also known as citrus greening disease) is the most devastating disease of citrus worldwide. It is caused by a bacterium ‘Candidatus Liberibacter asiaticus’ and transmitted by the Asian citrus psyllid (ACP), Diaphorina citri. Considerable research has been conducted toward...

Diaphorina citri (Hemiptera:Liviidae) abundance in Puerto Rico declines with elevation

USDA-ARS?s Scientific Manuscript database

Diaphorina citri is the primary vector of Hunglongbing disease, the most devastating disease of citrus. Diaphorina citri populations in Puerto Rico were monitored with yellow sticky traps on citrus trees at different elevations, ranging from 10 to 880 m above sea level. Trapping was conducted in Mar...

The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy.

PubMed

Regier, Debra S; Proia, Richard L; D'Azzo, Alessandra; Tifft, Cynthia J

2016-06-01

The gangliosidoses are lysosomal storage disorders caused by accumulation of GM1 or GM2 gangliosides. GM1 gangliosidosis has both central nervous system and systemic findings; while, GM2 gangliosidosis is restricted primarily to the central nervous system. Both disorders have autosomal recessive modes of inheritance and a continuum of clinical presentations from a severe infantile form to a milder, chronic adult form. Both are devastating diseases without cure or specific treatment however, with the use of supportive aggressive medical management, the lifespan and quality of life has been extended for both diseases. Naturally occurring and engineered animal models that mimic the human diseases have enhanced our understanding of the pathogenesis of disease progression. Some models have shown significant improvement in symptoms and lifespan with enzyme replacement, substrate reduction, and anti-inflammatory treatments alone or in combination. More recently gene therapy has shown impressive results in large and small animal models. Treatment with FDA-approved glucose analogs to reduce the amount of ganglioside substrate is used as off-label treatments for some patients. Therapies also under clinical development include small molecule chaperones and gene therapy.

Multi-Family Psychoeducational Support Group Therapy for Families with a Member Afflicted with Irreversible Brain Syndrome (Alzheimer's Disease): Report of a Pilot Study.

ERIC Educational Resources Information Center

Paley, Evelyn S.; And Others

Alzheimers Disease (AD), an incurable disability which afflicts older adults, can have devastating emotional consequences for the victim and the family. In an attempt to determine the effectiveness of multifamily psychoeducational support, group therapy (MFPSGT), 22 persons (13 families) from the Alzheimer's Disease and Related Disorders…

HIV and Cancer Interaction Highlights Need to Address Disease Stigma

Cancer.gov

The global landscape of disease highlights disparities that exist between nations. An estimated 36 million people worldwide live with HIV and AIDS, of which only 1 million are located within the United States. While the diagnosis of a life-threatening disease can be devastating, individuals with HIV and AIDS frequently bear an additional burden of stigma and discrimination.

Optimizing quality of life in patients with idiopathic pulmonary fibrosis

PubMed Central

van Manen, Mirjam J. G.; Geelhoed, J. J. Miranda.; Tak, Nelleke C.; Wijsenbeek, Marlies S.

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a devastating, progressive and ultimately fatal lung disease. The combination of poor prognosis, uncertainty of disease course and severe symptom burden heavily impacts patients’ and their families’ quality of life. Though new antifibrotic drugs have been shown to decrease disease progression, the effect on health-related quality of life (HRQOL) has not been convincingly demonstrated. In a relentless disease such as IPF, striving to optimize HRQOL should complement the endeavour to prolong life. Unfortunately, there is a paucity of interventions improving symptoms and functionality for patients with IPF, and research focusing on symptom improvement, and assessing and optimizing HRQOL, is limited. This review summarizes the most recent insights into measuring and improving quality of life for patients with IPF, and discusses challenges in the management of this devastating disease. Moreover, we postulate a new model for continuous care in IPF – ‘the ABCDE of IPF care’: Assessing patients’ needs; Backing patients by giving information and support; delivering Comfort care by focusing on treating symptoms and taking into account Comorbidities; striving to prolong life by Disease modification; helping and preparing patients and their caregivers for the eventual End-of-life events that are likely to occur. PMID:28134007

Proteostasis and Diseases of the Motor Unit.

PubMed

Rinaldi, Carlo; Mäger, Imre; Wood, Matthew J

2016-01-01

The accumulation in neurons of aberrant protein species, the pathological hallmark of many neurodegenerative diseases, results from a global impairment of key cellular processes governing protein synthesis/degradation and repair mechanisms, also known as the proteostasis network (PN). The growing number of connections between dysfunction of this intricate network of pathways and diseases of the motor unit, where both motor neurons and muscle are primarily affected, has provided momentum to investigate the muscle- and motor neuron-specific response to physiological and pathological stressors and to explore the therapeutic opportunities that manipulation of this process may offer. Furthermore, these diseases offer an unparalleled opportunity to deepen our understanding of the molecular mechanisms behind the intertissue communication and transfer of signals of proteostasis. The most compelling aspect of these investigations is their immediate potential for therapeutic impact: targeting muscle to stem degeneration of the motor unit would represent a dramatic paradigm therapeutic shift for treating these devastating diseases. Here we will review the current state of the art of the research on the alterations of the PN in diseases of the motor unit and its potential to result in effective treatments for these devastating neuromuscular disorders.

Teaching for Epistemological Difference: Decentring Norms in Environmental Studies

ERIC Educational Resources Information Center

Barrett, M. J.

2012-01-01

Many environmental educators and philosophers have identified anthropocentrism and the socially constructed separation between humans and "the more-than-human world" (Abram, 1996) as primary root causes of current ecological devastation. This separation is embedded in Western schooling content and structures and is often unintentionally…

Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases.

PubMed

Spudich, James A

2014-03-18

With the advent of technologies to obtain the complete sequence of the human genome in a cost-effective manner, this decade and those to come will see an exponential increase in our understanding of the underlying genetics that lead to human disease. And where we have a deep understanding of the biochemical and biophysical basis of the machineries and pathways involved in those genetic changes, there are great hopes for the development of modern therapeutics that specifically target the actual machinery and pathways altered by individual mutations. Prime examples of such a genetic disease are those classes of hypertrophic and dilated cardiomyopathy that result from single amino-acid substitutions in one of several of the proteins that make up the cardiac sarcomere or from the truncation of myosin binding protein C. Hypertrophic cardiomyopathy alone affects ∼1 in 500 individuals, and it is the leading cause of sudden cardiac death in young adults. Here I describe approaches to understand the molecular basis of the alterations in power output that result from these mutations. Small molecules binding to the mutant sarcomeric protein complex should be able to mitigate the effects of hypertrophic and dilated cardiomyopathy mutations at their sources, leading to possible new therapeutic approaches for these genetic diseases. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation.

PubMed

Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M

2015-07-01

Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Aluminium in brain tissue in familial Alzheimer's disease.

PubMed

Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

2017-03-01

The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease

PubMed Central

Chatterjee, Gaurav; McGraw, Claire; Kasturirangan, Srinath; Schulz, Philip

2012-01-01

Protein misfolding and aggregation is a critically important feature in many devastating neurodegenerative diseases, therefore characterization of the CSF concentration profiles of selected key forms and morphologies of proteins involved in these diseases, including β-amyloid (Aβ) and α-synuclein (a-syn), can be an effective diagnostic assay for these diseases. CSF levels of tau and Aβ have been shown to have great promise as biomarkers for Alzheimer’s disease. However since the onset and progression of many neurodegenerative diseases have been strongly correlated with the presence of soluble oligomeric aggregates of proteins including various Aβ and a-syn aggregate species, specific detection and quantification of levels of each of these different toxic protein species in CSF may provide a simple and accurate means to presymptomatically diagnose and distinguish between these diseases. Here we show that the presence of different protein morphologies in human CSF samples can be readily detected using highly selective morphology specific reagents in conjunction with a sensitive electronic biosensor. We further show that these morphology specific reagents can readily distinguish between post-mortem CSF samples from AD, PD and cognitively normal sources. These studies suggest that detection of specific oligomeric aggregate species holds great promise as sensitive biomarkers for neurodegenerative disease. PMID:22076255

The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon.

PubMed

Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K; Alcami, Antonio

2010-05-01

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.

Ten-year performance of the United States national elm trial

Treesearch

Jason J. Griffin; William R. Jacobi; E. Gregory McPherson; Clifford S. Sadof; James R. McKenna; Mark L. Gleason; Nicole Ward Gauthier; Daniel A. Potter; David R. Smitley; Gerard C. Adams; Ann Brooks Gould; Christian R. Cash; James A. Walla; Mark C. Starrett; Gary Chastagner; Jeff L. Sibley; Vera A. Krischik; Adam F. Newby

2017-01-01

Ulmus americana (American elm) was an important urban tree in North America prior to the introduction of the Dutch elm disease pathogen in 1930. Subsequently, urban and community forests were devastated by the loss of large canopies. Tree improvement programs produced disease tolerant American and Eurasian elm cultivars and introduced them into the...

Arabidopsis Thaliana Ecotypes With Differential Susceptibility To The Bacterial Pathogen Xylella fastidiosa

USDA-ARS?s Scientific Manuscript database

Pierce’s disease of grapes and almond leaf scorch are devastating diseases caused by the bacterium Xylella fastidiosa (Xf). To date, progress in determining the mechanisms of host plant susceptibility, tolerance or resistance has been slow, due in large part to the long generation time and limited a...

First report of frosty pod rot caused by Moniliophthora roreri on cacao in Bolivia

USDA-ARS?s Scientific Manuscript database

Frosty pod rot (FPR) is a devastating cacao disease caused by the basidiomycete Moniliophthora roreri (Aime and Phillips-Mora, 2005). The disease is confined to 13 countries in Central and South America and constitutes a permanent threat for cacao cultivation worldwide. In July 2012, FPR was detect...

Efficacy of an autodisseminator of an entomopathogenic fungus, Isaria fumosorosea, to suppress Asian citrus psyllid, Diaphorina citri, under greenhouse conditions

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid (ACP), transmits the causative agents of citrus greening disease or huanglongbing (HLB), the most devastating disease of citrus trees in the world today. ACP dwelling in noncommercial citrus (neighborhoods, commercial landscapes, etc.) can stymie area-wide management program...

Small RNA profiling reveals phosphorus deficiency as a contributing factor in symptom expression for Citrus Huanglongbing Disease

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus Candidatus Liberibacter(Ca. L.). Powerful diagnostic tools and management strategies are desired to control HLB. Host small Ribonucleic acid (sRNA) play a vital role in regulating host responses to pa...

Identification of blast resistance genes for managing rice blast disease

USDA-ARS?s Scientific Manuscript database

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases worldwide. In the present study, an international set of monogenic differentials carrying 24 major blast resistance (R) genes (Pia, Pib, Pii, Pik, Pik-h, Pik-m, Pik-p, Pik-s, Pish, Pit, Pita, Pita2,...

Comparison of different detection methods for citrus greening disease based on airborne multispectral and hyperspectral imagery

USDA-ARS?s Scientific Manuscript database

Citrus greening or Huanglongbing (HLB) is a devastating disease spread in many citrus groves since first found in 2005 in Florida. Multispectral (MS) and hyperspectral (HS) airborne images of citrus groves in Florida were taken to detect citrus greening infected trees in 2007 and 2010. Ground truthi...

Analysis of the genome sequence of Phomopsis longicolla: A fungal pathogen causing Phomopsis seed decay in soybean

USDA-ARS?s Scientific Manuscript database

Phomopsis longicolla T. W. Hobbs (syn. Diaporthe longicolla) is a seed-borne fungus causing Phomopsis seed decay in soybean. This disease is one of the most devastating diseases reducing soybean seed quality worldwide. To facilitate investigation of the genomic basis of pathogenicity and to understa...

Invasive plants, insects, and diseases in the forests of the Anthropocene

Treesearch

Alexander M. Evans

2014-01-01

Invasive species, non-native plants, insects, and diseases can devastate forests. They outcompete native species, replace them in the ecosystem, and even drive keystone forest species to functional extinction. Invasives have negative effects on forest hydrology, carbon storage, and nutrient cycling. The damage caused by invasive species exacerbates the other forest...

Laser Capture Microdissection and Multiplex-Tandem PCR Analysis of Proximal Tubular Epithelial Cell Signaling in Human Kidney Disease

PubMed Central

Wilkinson, Ray; Wang, Xiangju; Kassianos, Andrew J.; Zuryn, Steven; Roper, Kathrein E.; Osborne, Andrew; Sampangi, Sandeep; Francis, Leo; Raghunath, Vishwas; Healy, Helen

2014-01-01

Interstitial fibrosis, a histological process common to many kidney diseases, is the precursor state to end stage kidney disease, a devastating and costly outcome for the patient and the health system. Fibrosis is historically associated with chronic kidney disease (CKD) but emerging evidence is now linking many forms of acute kidney disease (AKD) with the development of CKD. Indeed, we and others have observed at least some degree of fibrosis in up to 50% of clinically defined cases of AKD. Epithelial cells of the proximal tubule (PTEC) are central in the development of kidney interstitial fibrosis. We combine the novel techniques of laser capture microdissection and multiplex-tandem PCR to identify and quantitate “real time” gene transcription profiles of purified PTEC isolated from human kidney biopsies that describe signaling pathways associated with this pathological fibrotic process. Our results: (i) confirm previous in-vitro and animal model studies; kidney injury molecule-1 is up-regulated in patients with acute tubular injury, inflammation, neutrophil infiltration and a range of chronic disease diagnoses, (ii) provide data to inform treatment; complement component 3 expression correlates with inflammation and acute tubular injury, (iii) identify potential new biomarkers; proline 4-hydroxylase transcription is down-regulated and vimentin is up-regulated across kidney diseases, (iv) describe previously unrecognized feedback mechanisms within PTEC; Smad-3 is down-regulated in many kidney diseases suggesting a possible negative feedback loop for TGF-β in the disease state, whilst tight junction protein-1 is up-regulated in many kidney diseases, suggesting feedback interactions with vimentin expression. These data demonstrate that the combined techniques of laser capture microdissection and multiplex-tandem PCR have the power to study molecular signaling within single cell populations derived from clinically sourced tissue. PMID:24475278

A Descriptive Survey of Inflammatory Bowel Disease within the Active Army Population (1971-1982).

DTIC Science & Technology

1985-06-01

psychological response to stress has an impact on the disease once it is established. This includes the recurrence of the disease as well as its severity. An...underlying question that remains is: Which is the causal agent, the disease or the psychological response to the disease? The inflammatory process of the... psychological factor. Only with increased knowledge of their epidemiologic factors will researchers begin to understand the basis for these devastating

Learning That Makes a Difference: Pedagogy and Practice for Learning Abroad

ERIC Educational Resources Information Center

Benham Rennick, Joanne

2015-01-01

Society faces significant new challenges surrounding issues in human health; global security; environmental devastation; human rights violations; economic uncertainty; population explosion and regression; recognition of diversity, difference and special populations at home and abroad. In light of these challenges, there is a great opportunity, and…

Biofortification: How can we exploit plant science and biotechnology to reduce micronutrient deficiencies?

USDA-ARS?s Scientific Manuscript database

Throughout the developing world, the long-term consequences of insufficient amounts of essential micronutrients in the human diet can be more devastating than low energy intake. Micronutrients are involved in all aspects of development, growth, and physiology of the human body (including from early ...

White-Nose Syndrome of bats

Treesearch

Jessie A. Glaeser; Martin J. Pfeiffer; Daniel L. Lindner

2016-01-01

Devastating. Catastrophic. Unprecedented. This is how white-nose syndrome of bats (WNS) is characterized. It is one of the deadliest wildlife diseases ever observed and could have significant impacts on outdoor recreation, agriculture and wildlife management.

Effect of changes in human ecology and behavior on patterns of sexually transmitted diseases, including human immunodeficiency virus infection.

PubMed Central

Wasserheit, J N

1994-01-01

The last 20 years have witnessed six striking changes in patterns of sexually transmitted diseases (STDs): emergence of new STD organisms and etiologies, reemergence of old STDs, shifts in the populations in which STDs are concentrated, shifts in the etiological spectra of STD syndromes, alterations in the incidence of STD complications, and increases in antimicrobial resistance. For example, human immunodeficiency virus (HIV) emerged to devastate the United States with a fatal pandemic involving at least 1 million people. The incidence of syphilis rose progressively after 1956 to reach a 40-year peak by 1990. In both cases, disease patterns shifted from homosexual men to include minority heterosexuals. Over the last decade, gonorrhea became increasingly concentrated among adolescents, and several new types of antimicrobial resistance appeared. Three interrelated types of environments affect STD patterns. The microbiologic, hormonal, and immunologic microenvironments most directly influence susceptibility, infectiousness, and development of sequelae. These microenvironments are shaped, in part, by the personal environments created by an individual's sexual, substance-use, and health-related behaviors. The personal environments are also important determinants of acquisition of infection and development of sequelae but, in addition, they mediate risk of exposure to infection. These are, therefore, the environments that most directly affect changing disease patterns. Finally, individuals' personal environments are, in turn, molded by powerful macroenvironmental forces, including socioeconomic, demographic, geographic, political, epidemiologic, and technological factors. Over the past 20 years, the profound changes that have occurred in many aspects of the personal environment and the macroenvironment have been reflected in new STD patterns. PMID:8146135

Seroprevalence of Baylisascaris procyonis infection among humans, Santa Barbara County, California, USA, 2014–2016

USGS Publications Warehouse

Weinstein, Sara B.; Lake, Camille M.; Chastain, Holly M.; Fisk, David; Handali, Sukwan; Kahn, Philip L.; Montgomery, Susan P.; Wilkins, Patricia P.; Kuris, Armand M.; Lafferty, Kevin D.

2017-01-01

Baylisascaris procyonis (raccoon roundworm) infection is common in raccoons and can cause devastating pathology in other animals, including humans. Limited information is available on the frequency of asymptomatic human infection. We tested 150 adults from California, USA, for B. procyonis antibodies; 11 were seropositive, suggesting that subclinical infection does occur.

Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

PubMed Central

Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

2013-01-01

Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

Metagenomic Sequencing for Surveillance of Food- and Waterborne Viral Diseases.

PubMed

Nieuwenhuijse, David F; Koopmans, Marion P G

2017-01-01

A plethora of viruses can be transmitted by the food- and waterborne route. However, their recognition is challenging because of the variety of viruses, heterogeneity of symptoms, the lack of awareness of clinicians, and limited surveillance efforts. Classical food- and waterborne viral disease outbreaks are mainly caused by caliciviruses, but the source of the virus is often not known and the foodborne mode of transmission is difficult to discriminate from human-to-human transmission. Atypical food- and waterborne viral disease can be caused by viruses such as hepatitis A and hepatitis E. In addition, a source of novel emerging viruses with a potential to spread via the food- and waterborne route is the repeated interaction of humans with wildlife. Wildlife-to-human adaptation may give rise to self- limiting outbreaks in some cases, but when fully adjusted to the human host can be devastating. Metagenomic sequencing has been investigated as a promising solution for surveillance purposes as it detects all viruses in a single protocol, delivers additional genomic information for outbreak tracing, and detects novel unknown viruses. Nevertheless, several issues must be addressed to apply metagenomic sequencing in surveillance. First, sample preparation is difficult since the genomic material of viruses is generally overshadowed by host- and bacterial genomes. Second, several data analysis issues hamper the efficient, robust, and automated processing of metagenomic data. Third, interpretation of metagenomic data is hard, because of the lack of general knowledge of the virome in the food chain and the environment. Further developments in virus-specific nucleic acid extraction methods, bioinformatic data processing applications, and unifying data visualization tools are needed to gain insightful surveillance knowledge from suspect food samples.

Metagenomic Sequencing for Surveillance of Food- and Waterborne Viral Diseases

PubMed Central

Nieuwenhuijse, David F.; Koopmans, Marion P. G.

2017-01-01

A plethora of viruses can be transmitted by the food- and waterborne route. However, their recognition is challenging because of the variety of viruses, heterogeneity of symptoms, the lack of awareness of clinicians, and limited surveillance efforts. Classical food- and waterborne viral disease outbreaks are mainly caused by caliciviruses, but the source of the virus is often not known and the foodborne mode of transmission is difficult to discriminate from human-to-human transmission. Atypical food- and waterborne viral disease can be caused by viruses such as hepatitis A and hepatitis E. In addition, a source of novel emerging viruses with a potential to spread via the food- and waterborne route is the repeated interaction of humans with wildlife. Wildlife-to-human adaptation may give rise to self- limiting outbreaks in some cases, but when fully adjusted to the human host can be devastating. Metagenomic sequencing has been investigated as a promising solution for surveillance purposes as it detects all viruses in a single protocol, delivers additional genomic information for outbreak tracing, and detects novel unknown viruses. Nevertheless, several issues must be addressed to apply metagenomic sequencing in surveillance. First, sample preparation is difficult since the genomic material of viruses is generally overshadowed by host- and bacterial genomes. Second, several data analysis issues hamper the efficient, robust, and automated processing of metagenomic data. Third, interpretation of metagenomic data is hard, because of the lack of general knowledge of the virome in the food chain and the environment. Further developments in virus-specific nucleic acid extraction methods, bioinformatic data processing applications, and unifying data visualization tools are needed to gain insightful surveillance knowledge from suspect food samples. PMID:28261185

H5N1 influenza viruses: outbreaks and biological properties

PubMed Central

Neumann, Gabriele; Chen, Hualan; Gao, George F; Shu, Yuelong; Kawaoka, Yoshihiro

2010-01-01

All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties. PMID:19884910

Vaccination against Alzheimer disease: an update on future strategies.

PubMed

Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

2014-01-01

Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer.

Vaccination against Alzheimer disease

PubMed Central

Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

2014-01-01

Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer. PMID:24535580

Examining the causes of a devastating debris flow

NASA Astrophysics Data System (ADS)

Balcerak, Ernie

2014-08-01

Storm-triggered landslides cause loss of life, property damage, and landscape alterations. For instance, the remnants of Hurricane Camille in 1969 caused 109 deaths in central Virginia, after 600 millimeters of rain fell in mountainous terrain in 6 hours. More recently, on 8 August 2010, a rainstorm-induced landslide devastated the Chinese county of Zhouqu, causing more than 1000 deaths. A new modeling study by Ren examines the multiple factors, natural and human caused, that came together to produce this event. Three things contribute to storm-triggered landslides: geological condition, surface loading and vegetation roots, and extreme precipitation.

Don't forget about the Christchurch earthquake: Lessons learned from this disaster

USGS Publications Warehouse

Hamburger, Michael W.; Mooney, Walter D.

2011-01-01

In the aftermath of the devastating magnitude-9.0 earthquake and tsunami that struck the Tohoku region of Japan on March 11, attention quickly turned away from a much smaller, but also highly destructive earthquake that struck the city of Christchurch, New Zealand, just a few weeks earlier, on Feb. 22. Both events are stark reminders of human vulnerability to natural disasters and provide a harsh reality check: Even technologically advanced countries with modern building codes are not immune from earthquake disasters. The Christchurch earthquake carried an additional message: Urban devastation can be triggered even by moderate-sized earthquakes.

Foot-and-mouth disease virus serotype O phylodynamics: genetic variability associated with epidemiological factors in Pakistan

USDA-ARS?s Scientific Manuscript database

One of the most challenging aspects of foot-and-mouth disease (FMD) control is the high genetic variability of the FMD virus (FMDV). In endemic settings such as the Indian subcontinent, this variability has resulted in the emergence of pandemic strains that have spread widely and caused devastating ...

Registration of OK05312, a high-yielding hard winter wheat donor of Cmc4 for wheat curl mite resistance

USDA-ARS?s Scientific Manuscript database

Wheat streak mosaic (WSM) is a devastating disease in the High Plains region that is advancing eastward toward lower elevations. Its control is best achieved by combining known disease resistance genes with resistance to the insect vector. A hard red winter (HRW) wheat (Triticum aestivum L.) germpla...

Frequency of Verticillium species in commercial spinach fields and transmission of V. dahliae from spinach to subsequent lettuce crops

USDA-ARS?s Scientific Manuscript database

Verticillium wilt, caused by Verticillium dahlia,e is a devastating disease of lettuce in California. The disease on lettuce is currently restricted to a small geographic area in the central coastal California, even though cropping patterns in other coastal lettuce production regions in the state ar...

Genes for wheat resistance ad susceptibility to Fusarium head blight and Septoria tritici blotch disease of wheat

USDA-ARS?s Scientific Manuscript database

Septoria tritici blotch (STB) and Fusarium head blight (FHB) are two of the most devastating diseases of wheat. Breeding for host resistance is an important component of integrated strategies for STB and FHB control. We identify genes and functional gene markers that can be used to expedite the proc...

A colorimetric bioassay for high-througput and cost-effectively assessing anti-foot-and-mouth disease virus activity

USDA-ARS?s Scientific Manuscript database

Foot-and-Mouth Disease virus (FMDV) is one of the most contagious animal viruses and has a devastating effect on livestock industries if an outbreaks occurs, especially in FMD-free countries. The virus is very sensitive to inhibition by type I interferons. Currently, a reported assay to measure FM...

Elm genetic diversity and hybridization in the presence of Dutch elm disease

USDA-ARS?s Scientific Manuscript database

Dutch elm disease (DED) has devastated native North American elm species for more than 75 years. The impact of DED on the genetic diversity of one native elm species, U. rubra or slippery elm, is summarized and its potential impact on the genetic diversity of the other four North American native elm...

Association analysis of bacterial leaf spot resistance and SNP markers derived from expressed sequence tags (ESTs) in lettuce (Lactuca sativa L.)

USDA-ARS?s Scientific Manuscript database

Bacterial leaf spot of lettuce, caused by Xanthomonas campestris pv. vitians, is a devastating disease of lettuce worldwide. Since there are no chemicals available for effective control of the disease, host-plant resistance is highly desirable to protect lettuce production. A total of 179 lettuce ge...

Combining 'omics and microscopy to visualize interactions between the Asian citrus psyllid vector and the Huanglongbing pathogen Candidatus Liberibacter asiaticus in the insect gut

USDA-ARS?s Scientific Manuscript database

Huanglongbing, or citrus greening disease, is an economically devastating bacterial disease of citrus. It is associated with infection by the gram-negative bacterium Candidatus Liberibacter asiaticus (CLas). CLas is transmitted by Diaphorina citri, the Asian citrus psyllid (ACP). For insect transmis...

Characterization of the microbial community structure in Candidatus Liberibacter asiaticus-infected citrus plants treated with antibiotics in the field

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) is one of the most devastating diseases of citrus worldwide. There are no effective control measures for this newly emerging and century-old disease. Previously, we reported a combination of Penicillin G and Streptomycin were effective in eliminating or suppressing the HLB bacter...

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

PubMed Central

Horowitz, Alana M.; Villeda, Saul A.

2017-01-01

Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans. PMID:28815019

Psychiatry between Glorification and Stigmatization.

PubMed

Sutovic, Alija

2017-12-01

In psychiatry, stigma means negative marking of the person only because s(he) has a diagnosis of mental disease, and usually this refers to schizophrenia. Stigmatization is related to prejudice, i.e. negative attitudes that are deeply rooted on false beliefs that schizophrenia cannot be treated. In principle, stigma is caused by combination of ignorance and fear which represents the basis of the creation of entrenched myths and prejudice. From a historical point of view, schizophrenia as a disease remains for public, one of the medical areas that are related to fear, a sense of discomfort, prejudice and avoidance. A combination of difficult mental disease, discrimination and stigmatization can be devastating for mentally disabled patients. Throughout history, stigma played significant role in patient's emotional and social isolation from other people deepening their suffering. A common consequence of stigma is discrimination which represents violation of basic human rights. Mentally disabled patients are often unjustifiably seen as dangerous, incapable, irresponsible which causes their isolation, homelessness and economic collapse. Thereby, possibilities for normal life, work, treatment, rehabilitation and social integration are decreased.

Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies

PubMed Central

Leal-Lopes, Camila; Velloso, Fernando J.; Campopiano, Julia C.; Sogayar, Mari C.; Correa, Ricardo G.

2015-01-01

The pancreas plays a central role in metabolism, allowing ingested food to be converted and used as fuel by the cells throughout the body. On the other hand, the pancreas may be affected by devastating diseases, such as pancreatitis, pancreatic adenocarcinoma (PAC), and diabetes mellitus (DM), which generally results in a wide metabolic imbalance. The causes for the development and progression of these diseases are still controversial; therefore it is essential to better understand the underlying mechanisms which compromise the pancreatic homeostasis. The interest in the study of the commensal microbiome increased extensively in recent years, when many discoveries have illustrated its central role in both human physiology and maintenance of homeostasis. Further understanding of the involvement of the microbiome during the development of pathological conditions is critical for the improvement of new diagnostic and therapeutic approaches. In the present review, we discuss recent findings on the behavior and functions played by the microbiota in major pancreatic diseases and provide further insights into its potential roles in the maintenance of pancreatic steady-state activities. PMID:26347203

Synucleins: are they two-edged swords?

PubMed

Surguchov, Andrei

2013-02-01

The synuclein family consists of three distinct highly homologous genes, α-synuclein, β-synuclein, and γ-synuclein, which have so far been found only in vertebrates. Proteins encoded by these genes are characterized by an acidic C-terminal region and five or six imperfect repeat motifs (KTKEGV) distributed throughout the highly conserved N-terminal region. Numerous data demonstrate that synucleins are implicated in two groups of the most devastating human disorders, i.e., neurodegenerative diseases (NDDs) and cancer. Mutations in the α-synuclein gene are associated with familial forms of Parkinson's disease (PD), and accumulation of α-synuclein inclusions is a hallmark of this disorder. In breast cancer, increased expression of γ-synuclein correlates with disease progression. Conversely, some results indicate that the members of the synuclein family may have a protective effect. How might these small proteins combine such controversial properties? We present evidence that synuclein's features are basically regulated by two mechanisms, i.e., posttranslational modifications (PTMs) and the level of their expression. We also discuss a new, emerging area of investigation of synucleins, namely, their role in the cell-to-cell propagation of pathology. Copyright © 2012 Wiley Periodicals, Inc.

RhoA/Rho-kinase signaling: a therapeutic target in pulmonary hypertension.

PubMed

Barman, Scott A; Zhu, Shu; White, Richard E

2009-01-01

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of the pulmonary vasculature. Both animal and clinical studies suggest that ROCK inhibitors are effective for treatment of severe PAH with minimal risk, which supports the premise that ROCKs are important therapeutic targets in pulmonary hypertension and that ROCK inhibitors are a promising new class of drugs for this devastating disease.

A Participatory System for Preventing Pandemics of Animal Origins: Pilot Study of the Participatory One Health Disease Detection (PODD) System

PubMed Central

Yano, Terdsak; Phornwisetsirikun, Somphorn; Susumpow, Patipat; Visrutaratna, Surasing; Chanachai, Karoon; Phetra, Polawat; Chaisowwong, Warangkhana; Trakarnsirinont, Pairat; Hemwan, Phonpat; Kaewpinta, Boontuan; Singhapreecha, Charuk; Kreausukon, Khwanchai; Charoenpanyanet, Arisara ; Robert, Chongchit Sripun; Robert, Lamar; Rodtian, Pranee; Mahasing, Suteerat; Laiya, Ekkachai; Pattamakaew, Sakulrat; Tankitiyanon, Taweesart; Sansamur, Chalutwan

2018-01-01

Background Aiming for early disease detection and prompt outbreak control, digital technology with a participatory One Health approach was used to create a novel disease surveillance system called Participatory One Health Disease Detection (PODD). PODD is a community-owned surveillance system that collects data from volunteer reporters; identifies disease outbreak automatically; and notifies the local governments (LGs), surrounding villages, and relevant authorities. This system provides a direct and immediate benefit to the communities by empowering them to protect themselves. Objective The objective of this study was to determine the effectiveness of the PODD system for the rapid detection and control of disease outbreaks. Methods The system was piloted in 74 LGs in Chiang Mai, Thailand, with the participation of 296 volunteer reporters. The volunteers and LGs were key participants in the piloting of the PODD system. Volunteers monitored animal and human diseases, as well as environmental problems, in their communities and reported these events via the PODD mobile phone app. LGs were responsible for outbreak control and provided support to the volunteers. Outcome mapping was used to evaluate the performance of the LGs and volunteers. Results LGs were categorized into one of the 3 groups based on performance: A (good), B (fair), and C (poor), with the majority (46%,34/74) categorized into group B. Volunteers were similarly categorized into 4 performance groups (A-D), again with group A showing the best performance, with the majority categorized into groups B and C. After 16 months of implementation, 1029 abnormal events had been reported and confirmed to be true reports. The majority of abnormal reports were sick or dead animals (404/1029, 39.26%), followed by zoonoses and other human diseases (129/1029, 12.54%). Many potentially devastating animal disease outbreaks were detected and successfully controlled, including 26 chicken high mortality outbreaks, 4 cattle disease outbreaks, 3 pig disease outbreaks, and 3 fish disease outbreaks. In all cases, the communities and animal authorities cooperated to apply community contingency plans to control these outbreaks, and community volunteers continued to monitor the abnormal events for 3 weeks after each outbreak was controlled. Conclusions By design, PODD initially targeted only animal diseases that potentially could emerge into human pandemics (eg, avian influenza) and then, in response to community needs, expanded to cover human health and environmental health issues. PMID:29563079

CE: Inside an Ebola Treatment Unit: A Nurse's Report.

PubMed

Wilson, Deborah

2015-12-01

In December 2013, the first cases of the most recent outbreak of Ebola virus disease (formerly known as Ebola hemorrhagic fever) emerged in the West African nation of Guinea. Within months the disease had spread to the neighboring countries of Liberia and Sierra Leone. The international humanitarian aid organization Médecins Sans Frontières (MSF; known in English as Doctors Without Borders) soon responded by sending staff to set up treatment centers and outreach triage teams in all three countries. In August 2014, the World Health Organization declared the outbreak an international public health emergency.In September 2014, the author was sent by MSF to work as a nurse in an Ebola treatment unit in Liberia for five weeks. This article describes her experiences there. It provides some background, outlines the practices and teams involved, and aims to convey a sense of what it's like to work during an Ebola outbreak and to put a human face on this devastating epidemic.

Recent advances in genes involved in secondary metabolite synthesis, hyphal development, energy metabolism and pathogenicity in Fusarium graminearum (teleomorph Gibberella zeae).

PubMed

Geng, Zongyi; Zhu, Wei; Su, Hao; Zhao, Yong; Zhang, Ke-Qin; Yang, Jinkui

2014-01-01

The ascomycete fungus, Fusarium graminearum (teleomorph Gibberella zeae), is the most common causal agent of Fusarium head blight (FHB), a devastating disease for cereal crops worldwide. F. graminearum produces ascospores (sexual spores) and conidia (asexual spores), which can serve as disease inocula of FHB. Meanwhile, Fusarium-infected grains are often contaminated with mycotoxins such as trichothecenes (TRIs), fumonisins, and zearalenones, among which TRIs are related to the pathogenicity of F. graminearum, and these toxins are hazardous to humans and livestock. In recent years, with the complete genome sequencing of F. graminearum, an increasing number of functional genes involved in the production of secondary metabolites, hyphal differentiation, sexual and asexual reproduction, virulence and pathogenicity have been identified from F. graminearum. In this review, the secondary metabolite synthesis, hyphal development and pathogenicity related genes in F. graminearum were thoroughly summarized, and the genes associated with secondary metabolites, sexual reproduction, energy metabolism, and pathogenicity were highlighted. Copyright © 2013 Elsevier Inc. All rights reserved.

Serum CEACAM1 Elevation Correlates with Melanoma Progression and Failure to Respond to Adoptive Cell Transfer Immunotherapy

PubMed Central

Ortenberg, R.; Sapoznik, S.; Zippel, D.; Shapira-Frommer, R.; Itzhaki, O.; Kubi, A.; Zikich, D.; Besser, M. J.; Schachter, J.; Markel, G.

2015-01-01

Malignant melanoma is a devastating disease whose incidences are continuously rising. The recently approved antimelanoma therapies carry new hope for metastatic patients for the first time in decades. However, the clinical management of melanoma is severely hampered by the absence of effective screening tools. The expression of the CEACAM1 adhesion molecule on melanoma cells is a strong predictor of poor prognosis. Interestingly, a melanoma-secreted form of CEACAM1 (sCEACAM1) has recently emerged as a potential tumor biomarker. Here we add novel evidences supporting the prognostic role of serum CEACAM1 by using a mice xenograft model of human melanoma and showing a correlation between serum CEACAM1 and tumor burden. Moreover, we demonstrate that serum CEACAM1 is elevated over time in progressive melanoma patients who fail to respond to immunotherapy as opposed to responders and stable disease patients, thus proving a correlation between sCEACAM1, response to treatment, and clinical deterioration. PMID:26688824

Phytophthora ramorum

USDA-ARS?s Scientific Manuscript database

Phytophthora ramorum is a recently emerged plant pathogen and causal agent of one of the most destructive and devastating diseases currently affecting US horticulture and forests. Formally described in 2001, P. ramorum is a filamentous, diploid protozoan that is one of 117 currently recognized Phyto...

DNA markers linked to the R2 rust resistance gene in sunflower (Helianthus annuus L.) facilitate anticipatory breeding for this disease variant

USDA-ARS?s Scientific Manuscript database

Pre-emptive breeding for host disease resistance is an effective strategy for combating and managing devastating incursions of plant pathogens. Comprehensive, long term studies have revealed that virulence to the R2 sunflower (Helianthus annuus L.) rust resistance gene in the line, MC29, does not ex...

The Italian elm breeding program for Dutch elm disease resistance

Treesearch

Alberto Santini; Francesco Pecori; Luisa Ghelardini

2012-01-01

In the 20th century, elms across Europe and North America were devastated by two pandemics of Dutch elm disease (DED), caused by the introduction of two fungal pathogens: Ophiostoma ulmi, followed by O. novo-ulmi. At the end of 1920s, research into a resistance to DED began in Europe and then in the United States. No...

Variable Number of Tandem Repeat Markers in the Genome Sequence of Mycosphaerella Fijiensis, the Causal Agent of Black Leaf Streak Disease of Banana (Musa spp.)

USDA-ARS?s Scientific Manuscript database

Mycosphaerella fijiensis, the causal agent of banana leaf streak disease (commonly known as black Sigatoka), is the most devastating pathogen attacking bananas (Musa spp). Recently the whole genome sequence of M. fijiensis became available. This sequence was screened for the presence of Variable Num...

Rhipicephalus appendiculatus ticks transmit theileria parva from persistently infected cattle in the absence of detectable parasitemia: implications for East Coast fever epidemiology

USDA-ARS?s Scientific Manuscript database

East Coast fever is a devastating disease of cattle caused by infection with the protozoan parasite, Theileria parva. Transmitted by the three-host tick, Rhipicephalus appendiculatus, the disease is present in 11 sub-Saharan African countries and is a major constraint to improvement of livestock pro...

HOW to Identify and Manage Dutch Elm Disease

Treesearch

Linda Haugen

1998-01-01

At one time, the American elm was considered to be an ideal street tree because it was graceful, long-lived, fast growing, and tolerant of compacted soils and air pollution. Then Dutch elm disease (DED) was introduced and began devastating the elm population. Estimates of DED losses of elm in communities and woodlands across the U.S. are staggering (figure 1). Because...

Elms and Dutch elm disease: a quick overview

Treesearch

Michael Marcotrigiano

2017-01-01

In the 1930s Dutch elm disease (DED) was accidentally introduced from Europe into the United States. It had a devastating impact on American elm (Ulmus americana) and its relatives in urban and riparian environments. In the United States, the three-part pathosystem for DED is unique in that the affected elm species are North American, the pathogen originated in Asia,...

USDA-ARS strategies to address the imminent threat of redbay ambrosia beetle and laurel wilt disease to avocados in Florida

USDA-ARS?s Scientific Manuscript database

Laurel wilt, a deadly fungal disease of avocado and other trees in the Lauraceae, is vectored by the redbay ambrosia beetle (Xyleborus glabratus). First detected in GA in 2002, the beetle has spread to SC and FL to within 70 miles of commercial avocado areas. Impact is potentially devastating to the...

Transcriptome analysis of sweet orange trees infected with ‘Candidatus Liberibacter asiaticus’ and two strains of citrus tristeza virus

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) and tristeza, are diseases of citrus caused by a member of the a-proteobacteria, ‘Candidatus Liberibacter asiaticus’ (CaLas), and Citrus tristeza virus (CTV) respectively. HLB is a devastating disease, but CTV strains vary from very severe to very mild. Both CaLas and CTV are p...

Devastating Transboundary Impacts of Sea Star Wasting Disease on Subtidal Asteroids.

PubMed

Montecino-Latorre, Diego; Eisenlord, Morgan E; Turner, Margaret; Yoshioka, Reyn; Harvell, C Drew; Pattengill-Semmens, Christy V; Nichols, Janna D; Gaydos, Joseph K

2016-01-01

Sea star wasting disease devastated intertidal sea star populations from Mexico to Alaska between 2013-15, but little detail is known about its impacts to subtidal species. We assessed the impacts of sea star wasting disease in the Salish Sea, a Canadian / United States transboundary marine ecosystem, and world-wide hotspot for temperate asteroid species diversity with a high degree of endemism. We analyzed roving diver survey data for the three most common subtidal sea star species collected by trained volunteer scuba divers between 2006-15 in 5 basins and on the outer coast of Washington, as well as scientific strip transect data for 11 common subtidal asteroid taxa collected by scientific divers in the San Juan Islands during the spring/summer of 2014 and 2015. Our findings highlight differential susceptibility and impact of sea star wasting disease among asteroid species populations and lack of differences between basins or on Washington's outer coast. Specifically, severe depletion of sunflower sea stars (Pycnopodia helianthoides) in the Salish Sea support reports of major declines in this species from California to Alaska, raising concern for the conservation of this ecologically important subtidal predator.

Devastating Transboundary Impacts of Sea Star Wasting Disease on Subtidal Asteroids

PubMed Central

Montecino-Latorre, Diego; Eisenlord, Morgan E.; Turner, Margaret; Yoshioka, Reyn; Harvell, C. Drew; Pattengill-Semmens, Christy V.; Nichols, Janna D.

2016-01-01

Sea star wasting disease devastated intertidal sea star populations from Mexico to Alaska between 2013–15, but little detail is known about its impacts to subtidal species. We assessed the impacts of sea star wasting disease in the Salish Sea, a Canadian / United States transboundary marine ecosystem, and world-wide hotspot for temperate asteroid species diversity with a high degree of endemism. We analyzed roving diver survey data for the three most common subtidal sea star species collected by trained volunteer scuba divers between 2006–15 in 5 basins and on the outer coast of Washington, as well as scientific strip transect data for 11 common subtidal asteroid taxa collected by scientific divers in the San Juan Islands during the spring/summer of 2014 and 2015. Our findings highlight differential susceptibility and impact of sea star wasting disease among asteroid species populations and lack of differences between basins or on Washington’s outer coast. Specifically, severe depletion of sunflower sea stars (Pycnopodia helianthoides) in the Salish Sea support reports of major declines in this species from California to Alaska, raising concern for the conservation of this ecologically important subtidal predator. PMID:27783620

Genetic modifiers of Huntington's disease.

PubMed

Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

2014-09-15

Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs. © 2014 International Parkinson and Movement Disorder Society.

Mitochondrial DNA sequence variation in human evolution and disease.

PubMed

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.

Toward a whole-body neuroprosthetic.

PubMed

Lebedev, Mikhail A; Nicolelis, Miguel A L

2011-01-01

Brain-machine interfaces (BMIs) hold promise for the restoration of body mobility in patients suffering from devastating motor deficits caused by brain injury, neurological diseases, and limb loss. Considerable progress has been achieved in BMIs that enact arm movements, and initial work has been done on BMIs for lower limb and trunk control. These developments put Duke University Center for Neuroengineering in the position to develop the first BMI for whole-body control. This whole-body BMI will incorporate very large-scale brain recordings, advanced decoding algorithms, artificial sensory feedback based on electrical stimulation of somatosensory areas, virtual environment representations, and a whole-body exoskeleton. This system will be first tested in nonhuman primates and then transferred to clinical trials in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Insight into Alternative Approaches for Control of Avian Influenza in Poultry, with Emphasis on Highly Pathogenic H5N1

PubMed Central

Abdelwhab, E. M.; Hafez, Hafez M.

2012-01-01

Highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 causes a devastating disease in poultry but when it accidentally infects humans it can cause death. Therefore, decrease the incidence of H5N1 in humans needs to focus on prevention and control of poultry infections. Conventional control strategies in poultry based on surveillance, stamping out, movement restriction and enforcement of biosecurity measures did not prevent the virus spreading, particularly in developing countries. Several challenges limit efficiency of the vaccines to prevent outbreaks of HPAIV H5N1 in endemic countries. Alternative and complementary approaches to reduce the current burden of H5N1 epidemics in poultry should be encouraged. The use of antiviral chemotherapy and natural compounds, avian-cytokines, RNA interference, genetic breeding and/or development of transgenic poultry warrant further evaluation as integrated intervention strategies for control of HPAIV H5N1 in poultry. PMID:23202521

Policy Options for Addressing Health System and Human Resources for Health Crisis in Liberia Post-Ebola Epidemic.

PubMed

Budy, Fidel C T

2015-01-01

Qualified healthcare workers within an effective health system are critical in promoting and achieving greater health outcomes such as those espoused in the Millennium Development Goals. Liberia is currently struggling with the effects of a brutal 14-year long civil war that devastated health infrastructures and caused most qualified health workers to flee and settle in foreign countries. The current output of locally trained health workers is not adequate for the tasks at hand. The recent Ebola Virus Disease (EVD) exposed the failings of the Liberian healthcare system. There is limited evidence of policies that could be replicated in Liberia to encourage qualified diaspora Liberian health workers to return and contribute to managing the phenomenon. This paper reviews the historical context for the human resources for health crisis in Liberia; it critically examines two context-specific health policy options to address the crisis, and recommends reverse brain drain as a policy option to address the immediate and critical crisis facing the health care sector in Liberia.

Naegleria fowleri: pathogenesis, diagnosis, and treatment options.

PubMed

Grace, Eddie; Asbill, Scott; Virga, Kris

2015-11-01

Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Naegleria fowleri: Pathogenesis, Diagnosis, and Treatment Options

PubMed Central

Grace, Eddie; Asbill, Scott

2015-01-01

Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America. PMID:26259797

Ebolavirus is evolving but not changing: No evidence for functional change in EBOV from 1976 to the 2014 outbreak.

PubMed

Olabode, Abayomi S; Jiang, Xiaowei; Robertson, David L; Lovell, Simon C

2015-08-01

The 2014 epidemic of Ebola virus disease (EVD) has had a devastating impact in West Africa. Sequencing of ebolavirus (EBOV) from infected individuals has revealed extensive genetic variation, leading to speculation that the virus may be adapting to humans, accounting for the scale of the 2014 outbreak. We computationally analyze the variation associated with all EVD outbreaks, and find none of the amino acid replacements lead to identifiable functional changes. These changes have minimal effect on protein structure, being neither stabilizing nor destabilizing, are not found in regions of the proteins associated with known functions and tend to cluster in poorly constrained regions of proteins, specifically intrinsically disordered regions. We find no evidence that the difference between the current and previous outbreaks is due to evolutionary changes associated with transmission to humans. Instead, epidemiological factors are likely to be responsible for the unprecedented spread of EVD. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

A LINE-1 Component to Human Aging: Do LINE elements exact a longevity cost for evolutionary advantage?

PubMed Central

Laurent, Georges St.; Hammell, Neil; McCaffrey, Timothy A.

2010-01-01

Advancing age remains the largest risk factor for devastating diseases, such as heart disease, stroke, and cancer. The mechanisms by which advancing age predisposes to disease are now beginning to unfold, due in part, to genetic and environmental manipulations of longevity in lower organisms. Converging lines of evidence suggest that DNA damage may be a final common pathway linking several proposed mechanisms of aging. The present review forwards a theory for an additional aging pathway that involves modes of inherent genetic instability. Long interspersed nuclear elements (LINEs) are endogenous non-LTR retrotransposons that compose about 20% of the human genome. The LINE-1 (L1) gene products, ORF1p and ORF2p, possess mRNA binding, endonuclease, and reverse transcriptase activity that enable retrotransposition. While principally active only during embryogenesis, L1 transcripts are detected in adult somatic cells under certain conditions. The present hypothesis proposes that L1s act as an ‘endogenous clock’, slowly eroding genomic integrity by competing with the organism’s double-strand break repair mechanism. Thus, while L1s are an accepted mechanism of genetic variation fueling evolution, it is proposed that longevity is negatively impacted by somatic L1 activity. The theory predicts testable hypotheses about the relationship between L1 activity, DNA repair, healthy aging, and longevity. PMID:20346965

Neurodegenerative signaling factors and mechanisms in Parkinson's pathology.

PubMed

Goswami, Poonam; Joshi, Neeraj; Singh, Sarika

2017-09-01

Parkinson's disease (PD) is a chronic and progressive degenerative disorder of central nervous system which is mainly characterized by selective loss of dopaminergic neurons in the nigrostrial pathway. Clinical symptoms of this devastating disease comprise motor impairments such as resting tremor, bradykinesia, postural instability and rigidity. Current medications only provide symptomatic relief but fail to halt the dopaminergic neuronal death. While the etiology of dopaminergic neuronal death is not fully understood, combination of various molecular mechanisms seems to play a critical role. Studies from experimental animal models have provided crucial insights into the molecular mechanisms in disease pathogenesis and recognized possible targets for therapeutic interventions. Recent findings implicate the involvement of abnormal protein accumulation and phosphorylation, mitochondrial dysfunction, oxidative damage and deregulated kinase signaling as key molecular mechanisms affecting the normal function as well survival of dopaminergic neurons. Here we discuss the relevant findings on the PD pathology related mechanisms and recognition of the cell survival mechanisms which could be used as targets for neuroprotective strategies in preventing this devastating disorder. Copyright © 2017 Elsevier Ltd. All rights reserved.

Strategies in Ebola virus disease (EVD) diagnostics at the point of care.

PubMed

Coarsey, Chad T; Esiobu, Nwadiuto; Narayanan, Ramswamy; Pavlovic, Mirjana; Shafiee, Hadi; Asghar, Waseem

2017-11-01

Ebola virus disease (EVD) is a devastating, highly infectious illness with a high mortality rate. The disease is endemic to regions of Central and West Africa, where there is limited laboratory infrastructure and trained staff. The recent 2014 West African EVD outbreak has been unprecedented in case numbers and fatalities, and has proven that such regional outbreaks can become a potential threat to global public health, as it became the source for the subsequent transmission events in Spain and the USA. The urgent need for rapid and affordable means of detecting Ebola is crucial to control the spread of EVD and prevent devastating fatalities. Current diagnostic techniques include molecular diagnostics and other serological and antigen detection assays; which can be time-consuming, laboratory-based, often require trained personnel and specialized equipment. In this review, we discuss the various Ebola detection techniques currently in use, and highlight the potential future directions pertinent to the development and adoption of novel point-of-care diagnostic tools. Finally, a case is made for the need to develop novel microfluidic technologies and versatile rapid detection platforms for early detection of EVD.

World Organisation for Animal Health: strengthening Veterinary Services for effective One Health collaboration.

PubMed

Corning, S

2014-08-01

To effectively reduce health risks at the animal-human-ecosystems interface, a One Health strategy is crucially important to create strong national and regional animal health systems that are well coordinated with strong public health systems. Animal diseases, particularly those caused by new and emerging zoonotic pathogens, must be effectively controlled at their source to reduce their potentially devastating impact upon both animal and human health. As the international organisation responsible for developing standards, guidelines and recommendations for animal health, the World Organisation for Animal Health (OIE) plays an important role in minimising animal and public health risks attributable to zoonoses and other animal diseases, which can have severe consequences for global food safety and security. National Veterinary Services, which implement OIE animal health and welfare standards and other measures, are the first line of defence against these diseases, and must have the capacity to meet the core requirements necessary for their diagnosis and control. The OIE works collaboratively with the World Health Organization and Food and Agriculture Organization of the United Nations to improve the ability of national animal and public health systems to respond to current and emerging animal health risks with public health consequences. In addition to improving and aligning national laboratory capacities in high-risk areas, the OIE collaborates on One Health-oriented projects for key diseases, establishing model frameworks which can be applied to manage other existing and emerging priority diseases. This article reviews the role and activities of the OIE in strengthening the national Veterinary Services of its Member Countries for a more effective and sustainable One Health collaboration.

Ophiostomatoid fungi associated with invasive Tetropium spp. (Fabr.) (Coleoptera:Cerambycidae) in Atlantic Canada.

Treesearch

Karin Jacobs; Keith A. Seifert; Ken J. Harrison; Georgette Smith; Thomas Kirisits

2003-01-01

Species of the Ascomycete genus Ophiostoma are well-known for causing stain in living trees and lumber, as well as devastating pathogens, for example O. ulmi and O. novo-ulmi, the causes of Dutch elm disease.

Invasive streptococcal disease: a review for clinicians.

PubMed

Parks, Tom; Barrett, Lucinda; Jones, Nicola

2015-09-01

Streptococci are a genus of Gram-positive bacteria which cause diverse human diseases. Many of these species have the potential to cause invasive infection resulting from the presence of bacteria in a normally sterile site. Original articles, reviews and guidelines. Invasive infection by a streptococcus species usually causes life-threatening illness. When measured in terms of deaths, disability and cost, these infections remain an important threat to health in the UK. Overall they are becoming more frequent among the elderly and those with underlying chronic illness. New observational evidence has become available to support the use of clindamycin and intravenous immunoglobulin in invasive Group A streptococcal disease. Few interventions for the treatment and prevention of these infections have undergone rigorous evaluation in clinical trials. For example, the role of preventative strategies such as screening of pregnant women to prevent neonatal invasive Group B streptococcal disease needs to be clarified. Studies of invasive streptococcal disease are challenging to undertake, not least because individual hospitals treat relatively few confirmed cases. Instead clinicians and scientists must work together to build national and international networks with the aim of developing a more complete evidence base for the treatment and prevention of these devastating infections. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular Dynamics Simulations of the Human Glucose Transporter GLUT1

PubMed Central

Park, Min-Sun

2015-01-01

Glucose transporters (GLUTs) provide a pathway for glucose transport across membranes. Human GLUTs are implicated in devastating diseases such as heart disease, hyper- and hypo-glycemia, type 2 diabetes and caner. The human GLUT1 has been recently crystalized in the inward-facing open conformation. However, there is no other structural information for other conformations. The X-ray structures of E. coli Xylose permease (XylE), a glucose transporter homolog, are available in multiple conformations with and without the substrates D-xylose and D-glucose. XylE has high sequence homology to human GLUT1 and key residues in the sugar-binding pocket are conserved. Here we construct a homology model for human GLUT1 based on the available XylE crystal structure in the partially occluded outward-facing conformation. A long unbiased all atom molecular dynamics simulation starting from the model can capture a new fully opened outward-facing conformation. Our investigation of molecular interactions at the interface between the transmembrane (TM) domains and the intracellular helices (ICH) domain in the outward- and inward-facing conformation supports that the ICH domain likely stabilizes the outward-facing conformation in GLUT1. Furthermore, inducing a conformational transition, our simulations manifest a global asymmetric rocker switch motion and detailed molecular interactions between the substrate and residues through the water-filled selective pore along a pathway from the extracellular to the intracellular side. The results presented here are consistent with previously published biochemical, mutagenesis and functional studies. Together, this study shed light on the structure and functional relationships of GLUT1 in multiple conformational states. PMID:25919356

COST EFFECTIVE SEAWATER DESALINATION WITH FICP ELEMENT ARRAYS - PHASE II

EPA Science Inventory

Lack of fresh water hinders economic development, devastates human health, leads to environmental degradation and foments political instability. We obtain our water from limited and unevenly distributed surface and underground freshwater sources. Over withdrawal from these ...

Cholera in Zimbabwe: Developing an Educational Response to a Health Crisis

ERIC Educational Resources Information Center

Mandikonza, Caleb; Musindo, Beatrice; Taylor, Jim

2011-01-01

In February 2009, the World Health Organization (WHO) reported that the cholera epidemic in Zimbabwe had claimed 3,300 lives and infected 66,000 people--greater than the toll of that disease in the whole of Africa in most years. How is it possible that a disease such as cholera can have such a devastating effect in modern times? How should one…

Unraveling the Mysteries of Progeria | Center for Cancer Research

Cancer.gov

Hutchinson-Gilford progeria syndrome is a rare and devastating genetic disorder in which patients appear normal at birth, but by 12 to 18 months display signs of premature aging such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Because no treatments currently exist, most patients with progeria die in their mid-teens from heart disease or stroke.

The High-Level Radioactive Waste Policy Dilemma: Prospects for a Realistic Management Policy

ERIC Educational Resources Information Center

Hadjilambrinos, Constantine

2006-01-01

Since the dawn of the atomic age, the United States and every other nation that has chosen to use nuclear power have created hazardous substances that have the capacity to outlast human civilization, and possibly even the human species, and the potential to devastate the environment. The management of these substances that make up what has been…

Fire blight resistance in wild accessions of Malus sieversii

USDA-ARS?s Scientific Manuscript database

Fire blight (Erwinia amylovora) is a devastating bacterial disease in apple that results in severe economic losses. Epidemics are becoming more common as susceptible cultivars and rootstocks are being planted, and control is becoming more difficult as antibiotic-resistant strains develop. Resistan...

Erwinia tracheiphila colonization of cantaloupe fruits through flower inoculation

USDA-ARS?s Scientific Manuscript database

Cantaloupe (Cucumis melo var. cantalupensis) is a nutritious fresh fruit. Bacterial wilt, caused by Erwinia tracheiphila, is the most devastating cantaloupe disease globally. The pathogen is transmitted in nature by xylem-feeding spotted and striped cucumber beetles; other modes of infection have ...

Nutritional requirements for soybean cyst nematode

USDA-ARS?s Scientific Manuscript database

Soybeans [Glycine max] are the second largest cash crop in US Agriculture, but the soybean yield is compromised by infections from Heterodera glycines, also known as Soybean Cyst Nematodes [SCN]. SCN are the most devastating pathogen or plant disease soybean producers confront. This obligate parasi...

Theodore E. Woodward Award: The devastating backlash of a dread disease: poliomyelitis.

PubMed

Billings, F Tremaine; Collins, Robert D

2005-01-01

The paper is in three parts. 1) A description of acute anterior poliomyelitis; 2) A summary of the condition of post-polio syndrome; 3) A description of two small epidemics of poliomyelitis juxtaposed and related to one another.

Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

PubMed

Willet, Cali E; Makara, Mariano; Reppas, George; Tsoukalas, George; Malik, Richard; Haase, Bianca; Wade, Claire M

2015-01-01

Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant). Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

The impact of HIV/AIDS on human development in African countries.

PubMed

Boutayeb, Abdesslam

2009-11-18

In the present paper, we consider the impact of HIV/AIDS on human development in African countries, showing that, beyond health issues, this disease should and must be seen as a global development concern, affecting all components of human development. Consequently, we stress the necessity of multidisciplinary approaches that model, estimate and predict the real impact of HIV/AIDS on human development of African countries in order to optimise the strategies proposed by national countries, international institutions and their partners. In our search strategy, we relied on secondary information, mainly through National Human Development Reports of some African countries and regular publications released by the United Nations (UN), United Nations Development Programme (UNDP), World Health Organization (WHO) and the World Bank. We restricted ourselves to reports dealing explicitly with the impact of HIV/AIDS on human development in African countries. HIV/AIDS is affecting the global human development of African countries through its devastating impact on health and demographic indicators such as life expectancy at birth, healthcare assistance, age and sex distribution, economic indicators like income, work force, and economic growth, education and knowledge acquisition and other indicators like governance, gender inequality and human rights. On the basis of the national reports reviewed, it appears clearly that HIV/AIDS is no longer a crisis only for the healthcare sector, but presents a challenge to all sectors. Consequently, HIV/AIDS is a development question and should be viewed as such. The disease is impeding development by imposing a steady decline in the key indicators of human development and hence reversing the social and economic gains that African countries are striving to attain. Being at the same time a cause and consequence of poverty and underdevelopment, it constitutes a challenge to human security and human development by diminishing the chances of alleviating poverty and hunger, achieving universal primary education, promoting gender equality, reducing child and maternal mortality, and ensuring environmental sustainability.

A current view of Alzheimer's disease.

PubMed

Hooli, Basavaraj V; Tanzi, Rudolph E

2009-07-08

Several genes that influence susceptibility to Alzheimer's disease (AD) have been known for over two decades. Recent advances have elucidated novel candidate genes and the pathogenetic mechanisms underlying neurodegeneration in AD. Here, we summarize what we have learned from studies of the known AD genes with regard to the causes of AD and emerging therapies. We also review key recent discoveries that have enhanced our understanding of the etiology and pathogenesis of this devastating disease, based on new investigations into the genes and molecular mechanisms underlying AD.

Genetic architecture of downy mildew resistance in cucumber

USDA-ARS?s Scientific Manuscript database

Downy mildew (DM) caused by the obligate oomycete Pseudoperonospora cubensis is the most devastating fungal disease to cucumber production. The molecular mechanism of DM resistance in cucumber is not well understood. We conducted QTL mapping for DM resistances in four cucumber lines including WI7120...

Theodore E. Woodward Award: The Devastating Backlash of a Dread Disease: Poliomyelitis

PubMed Central

Billings, F. Tremaine; Collins, Robert D

2005-01-01

The paper is in three parts. 1) A description of acute anterior poliomyelitis; 2) A summary of the condition of post-polio syndrome; 3) A description of two small epidemics of poliomyelitis juxtaposed and related to one another. PMID:16555605

Host preference of the vector beetle, host resistance, and expanding patterns of Japanese oak wilt in a stand

Treesearch

Kazuyoshi Futai; Hiroaki Kiku; Hong-ye Qi; Hagus Tarn; Yuko Takeuchi; Michimasa Yamasaki

2012-01-01

Since the early 1980s, an epidemic forest disease, Japanese Oak Wilt (JOW), has been spreading from coastal areas along the Sea of Japan to the interior of Honshu island and has been devastating huge areas of forests by killing an enormous number of oak trees in urban fringe mountains, gardens, and parks. The disease is caused by a fungus, Raffaelea...

[Historical and biological approaches to the study of Modern Age French plague mass burials].

PubMed

Bianuccii, Raffaella; Tzortzis, Stéfan; Fornaciari, Gino; Signoli, Michel

2010-01-01

The "Black Death" and subsequent epidemics from 1346 to the early 18th century spread from the Caspian Sea all over Europe six hundred years after the outbreak of the Justinian plague (541-767 AD). Plague has been one of the most devastating infectious diseases that affected the humankind and has caused approximately 200 million human deaths historically. Here we describe the different approaches adopted in the study of several French putative plague mass burials dating to the Modern Age (16th-18th centuries). Through complementation of historical, archaeological and paleobiological data, ample knowledge of both the causes that favoured the spread of the Medieval plague in cities, towns and small villages and of the modification of the customary funerary practices in urban and rural areas due to plague are gained.

Fungal model systems and the elucidation of pathogenicity determinants

PubMed Central

Perez-Nadales, Elena; Almeida Nogueira, Maria Filomena; Baldin, Clara; Castanheira, Sónia; El Ghalid, Mennat; Grund, Elisabeth; Lengeler, Klaus; Marchegiani, Elisabetta; Mehrotra, Pankaj Vinod; Moretti, Marino; Naik, Vikram; Oses-Ruiz, Miriam; Oskarsson, Therese; Schäfer, Katja; Wasserstrom, Lisa; Brakhage, Axel A.; Gow, Neil A.R.; Kahmann, Regine; Lebrun, Marc-Henri; Perez-Martin, José; Di Pietro, Antonio; Talbot, Nicholas J.; Toquin, Valerie; Walther, Andrea; Wendland, Jürgen

2014-01-01

Fungi have the capacity to cause devastating diseases of both plants and animals, causing significant harvest losses that threaten food security and human mycoses with high mortality rates. As a consequence, there is a critical need to promote development of new antifungal drugs, which requires a comprehensive molecular knowledge of fungal pathogenesis. In this review, we critically evaluate current knowledge of seven fungal organisms used as major research models for fungal pathogenesis. These include pathogens of both animals and plants; Ashbya gossypii, Aspergillus fumigatus, Candida albicans, Fusarium oxysporum, Magnaporthe oryzae, Ustilago maydis and Zymoseptoria tritici. We present key insights into the virulence mechanisms deployed by each species and a comparative overview of key insights obtained from genomic analysis. We then consider current trends and future challenges associated with the study of fungal pathogenicity. PMID:25011008

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.

PubMed

Ronald, John A; Kim, Byung-Su; Gowrishankar, Gayatri; Namavari, Mohammad; Alam, Israt S; D'Souza, Aloma; Nishikii, Hidekazu; Chuang, Hui-Yen; Ilovich, Ohad; Lin, Chih-Feng; Reeves, Robert; Shuhendler, Adam; Hoehne, Aileen; Chan, Carmel T; Baker, Jeanette; Yaghoubi, Shahriar S; VanBrocklin, Henry F; Hawkins, Randall; Franc, Benjamin L; Jivan, Salma; Slater, James B; Verdin, Emily F; Gao, Kenneth T; Benjamin, Jonathan; Negrin, Robert; Gambhir, Sanjiv Sam

2017-06-01

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893-902. ©2017 AACR . ©2017 American Association for Cancer Research.

Antimicrobial peptides in marine invertebrate health and disease

PubMed Central

Destoumieux-Garzón, Delphine; Rosa, Rafael Diego; Schmitt, Paulina; Barreto, Cairé; Vidal-Dupiol, Jeremie; Mitta, Guillaume; Gueguen, Yannick; Bachère, Evelyne

2016-01-01

Aquaculture contributes more than one-third of the animal protein from marine sources worldwide. A significant proportion of aquaculture products are derived from marine protostomes that are commonly referred to as ‘marine invertebrates’. Among them, penaeid shrimp (Ecdysozosoa, Arthropoda) and bivalve molluscs (Lophotrochozoa, Mollusca) are economically important. Mass rearing of arthropods and molluscs causes problems with pathogens in aquatic ecosystems that are exploited by humans. Remarkably, species of corals (Cnidaria) living in non-exploited ecosystems also suffer from devastating infectious diseases that display intriguing similarities with those affecting farmed animals. Infectious diseases affecting wild and farmed animals that are present in marine environments are predicted to increase in the future. This paper summarizes the role of the main pathogens and their interaction with host immunity, with a specific focus on antimicrobial peptides (AMPs) and pathogen resistance against AMPs. We provide a detailed review of penaeid shrimp AMPs and their role at the interface between the host and its resident/pathogenic microbiota. We also briefly describe the relevance of marine invertebrate AMPs in an applied context. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160602

Importance of Apolipoprotein A-I in Multiple Sclerosis.

PubMed

Gardner, Lidia A; Levin, Michael C

2015-01-01

Jean-Martin Charcot has first described multiple sclerosis (MS) as a disease of the central nervous system (CNS) over a century ago. MS remains incurable today, and treatment options are limited to disease modifying drugs. Over the years, significant advances in understanding disease pathology have been made in autoimmune and neurodegenerative components. Despite the fact that brain is the most lipid rich organ in human body, the importance of lipid metabolism has not been extensively studied in this disorder. In MS, the CNS is under attack by a person's own immune system. Autoantigens and autoantibodies are known to cause devastation of myelin through up regulation of T-cells and cytokines, which penetrate through the blood-brain barrier to cause inflammation and myelin destruction. The anti-inflammatory role of high-density lipoproteins (HDLs) has been implicated in a plethora of biological processes: vasodilation, immunity to infection, oxidation, inflammation, and apoptosis. However, it is not known what role HDL plays in neurological function and myelin repair in MS. Understanding of lipid metabolism in the CNS and in the periphery might unveil new therapeutic targets and explain the partial success of some existing MS therapies.

Antimicrobial peptides in marine invertebrate health and disease.

PubMed

Destoumieux-Garzón, Delphine; Rosa, Rafael Diego; Schmitt, Paulina; Barreto, Cairé; Vidal-Dupiol, Jeremie; Mitta, Guillaume; Gueguen, Yannick; Bachère, Evelyne

2016-05-26

Aquaculture contributes more than one-third of the animal protein from marine sources worldwide. A significant proportion of aquaculture products are derived from marine protostomes that are commonly referred to as 'marine invertebrates'. Among them, penaeid shrimp (Ecdysozosoa, Arthropoda) and bivalve molluscs (Lophotrochozoa, Mollusca) are economically important. Mass rearing of arthropods and molluscs causes problems with pathogens in aquatic ecosystems that are exploited by humans. Remarkably, species of corals (Cnidaria) living in non-exploited ecosystems also suffer from devastating infectious diseases that display intriguing similarities with those affecting farmed animals. Infectious diseases affecting wild and farmed animals that are present in marine environments are predicted to increase in the future. This paper summarizes the role of the main pathogens and their interaction with host immunity, with a specific focus on antimicrobial peptides (AMPs) and pathogen resistance against AMPs. We provide a detailed review of penaeid shrimp AMPs and their role at the interface between the host and its resident/pathogenic microbiota. We also briefly describe the relevance of marine invertebrate AMPs in an applied context.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. © 2016 The Author(s).

Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations

PubMed Central

Gerlai, Robert; Ahmad, Fahad; Prajapati, Sonal

2009-01-01

Background With the arsenal of genetic tools available for zebrafish, this species has been successfully used to investigate the genetic aspects of human diseases from developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing as CNS disorders may be modeled and studied with this species. Alcoholism and alcohol abuse are among the most devastating and costliest diseases. However, the mechanisms of these diseases are not fully understood. Zebrafish has been proposed as a model organism to study such mechanisms. Characterization of alcohol’s effects on zebrafish is a necessary step in this research. Methods Here, we compare the effects of acute alcohol (EtOH) administration on the behavior of zebrafish from 4 distinct laboratory-bred populations using automated as well as observation based behavioral quantification methods. Results Alcohol treatment resulted in significant dose-dependent behavioral changes but the dose–response trajectories differed among zebrafish populations. Conclusions The results demonstrate for the first time a genetic component in alcohol responses in adult zebrafish and also show the feasibility of high throughput behavioral screening. We discuss the exploration and exploitation of the genetic differences found. PMID:18652595

Underground Tank Management.

ERIC Educational Resources Information Center

Bednar, Barbara A.

1990-01-01

The harm to human health and our environment caused by leaking underground storage tanks can be devastating. Schools can meet new federal waste management standards by instituting daily inventory monitoring, selecting a reliable volumetric testing company, locating and repairing leaks promptly, and removing and installing tanks appropriately. (MLH)

Machine learning for characterization of insect vector feeding

USDA-ARS?s Scientific Manuscript database

Insects that feed by ingesting plant and animal fluids cause devastating damage to humans, livestock, and agriculture worldwide, primarily by transmitting pathogens of plants and animals. The feeding processes required for successful pathogen transmission by sucking insects can be recorded by monito...

Coverage of Jade Goody's cervical cancer in UK newspapers: a missed opportunity for health promotion?

PubMed Central

2010-01-01

Background It has been claimed that publicity surrounding popular celebrity Jade Goody's experience of cervical cancer will raise awareness about the disease. This study examines the content of newspaper articles covering her illness to consider whether 'mobilising information' which could encourage women to adopt risk-reducing and health promoting behaviours has been included. Methods Content analysis of 15 national newspapers published between August 2008 and April 2009 Findings In the extensive coverage of Goody's illness (527 articles in the 7 months of study) few newspaper articles included information that might make women more aware of the signs and symptoms or risk factors for the disease, or discussed the role of the human papilloma virus (HPV) and the recently introduced HPV vaccination programme to reduce the future incidence of cervical cancer. For example, less than 5% of articles mentioned well-known risk-factors for cervical cancer and less than 8% gave any information about HPV. The 'human interest' aspects of Goody's illness (her treatment, the spread of her disease in later months, her wedding, and her preparations for her children's future) were more extensively covered. Conclusions Newspaper coverage of Goody's illness has tended not to include factual or educational information that could mobilise or inform women, or help them to recognise early symptoms. However, the focus on personal tragedy may encourage women to be receptive to HPV vaccination or screening if her story acts as a reminder that cervical cancer can be a devastating and fatal disease in the longer term. PMID:20576115

Nanomedicine for prion disease treatment: new insights into the role of dendrimers.

PubMed

McCarthy, James M; Appelhans, Dietmar; Tatzelt, Jörg; Rogers, Mark S

2013-01-01

Despite their devastating impact, no effective therapeutic yet exists for prion diseases at the symptomatic stage in humans or animals. Progress is hampered by the difficulty in identifying compounds that affect PrP (Sc) and the necessity of any potential therapeutic to gain access to the CNS. Synthetic polymers known as dendrimers are a particularly promising candidate in this area. Studies with cell culture models of prion disease and prion infected brain homogenate have demonstrated that numerous species of dendrimers eliminate PrP (Sc) in a dose and time dependent fashion and specific glycodendrimers are capable of crossing the CNS. However, despite their potential a number of important questions remained unanswered such as what makes an effective dendrimer and how dendrimers eliminate prions intracellularly. In a number of recent studies we have tackled these questions and revealed for the first time that a specific dendrimer can inhibit the intracellular conversion of PrP (C) to PrP (Sc) and that a high density of surface reactive groups is a necessity for dendrimers in vitro anti-prion activity. Understanding how a therapeutic works is a vital component in maximising its activity and these studies therefore represent a significant development in the race to find effective treatments for prion diseases.

Fatty Acid Methyl Ester (FAME) analyses for characterization and detection of grapevine pathogens

USDA-ARS?s Scientific Manuscript database

Grapevines can become infected by a variety of devastating pathogens, including the bacterium Xylella fastidiosa and canker fungi. Multiple strains of Xylella fastidiosa exist, each causing different diseases on various hosts. Although sequence-based genotyping can assist in distinguishing these str...

Selected techniques and protocols in American foulbrood research

USDA-ARS?s Scientific Manuscript database

American foulbrood is one of the most devastating diseases of the honey bee caused by the spore-forming, Gram-positive rod-shaped bacterium Paenibacillus larvae. The recent updated genome assembly and annotation of this pathogen now permits in depth molecular studies. In the present paper, selecte...

Behavioral assay on Asian citrus psyllid attraction to orange jasmine

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid (ACP) is an important pest because it transmits a bacterium putatively responsible for huanglongbing, a devastating citrus disease. Research on ACP chemical ecology is of interest with respect to identifying attractants and repellents for managing the psyllid. We report on a...

Microbial Scourges and Their Impact on Health.

ERIC Educational Resources Information Center

Howell, Dennis G.; Soltys, Marian A.

1982-01-01

A review of great epidemics (rat-borne, plague, smallpox, cholera, influenza, rabies, tuberculosis) reveals the devastation they have caused. Success in the battle against these is being won through hygiene, sanitation, vector control, and vaccines, especially since microbiology has provided a rational understanding of the diseases. (Author/JN)

Dissecting black spot resistance in polyploid hybrid roses

USDA-ARS?s Scientific Manuscript database

Devastating foliar diseases, such as black spot caused by Diplocarpon rosae, pose constant threats to the ornamental quality of outdoor grown roses. Black spot is primarily managed though the use of fungicides, however, there is a high demand for resistant roses which require low chemical inputs. To...

Synthetic substrate-borne vibrational signals that elicit Asian citrus psyllid communicatory and search responses

USDA-ARS?s Scientific Manuscript database

The Asian Citrus Psyllid (ACP), Diaphorina citri Kuwayama, vectors a harmful bacterium, Candidatus Liberibacter asiaticus, that causes huanglongbing, an economically devastating disease of citrus. Adult male and female ACP transmit vibratory communication signals over 10-50-cm distances within their...

Particle exposure and the historical loss of Native American lives to infections

EPA Science Inventory

This is a letter to the editor-excerpt: An alternative reason for the devastating loss of Native American lives to infectious diseases introduced through interactions with Europeans could include an impact of exposure to particulate matter (PM) associated with the preparation of...

Strategies in Ebola virus disease (EVD) diagnostics at the point of care

PubMed Central

Coarsey, Chad T.; Esiobu, Nwadiuto; Narayanan, Ramswamy; Pavlovic, Mirjana; Shafiee, Hadi; Asghar, Waseem

2017-01-01

Ebola virus disease (EVD) is a devastating, highly infectious illness with a high mortality rate. The disease is endemic to regions of Central and West Africa, where there is limited laboratory infrastructure and trained staff. The recent 2014 West African EVD outbreak has been unprecedented in case numbers and fatalities, and has proven that such regional outbreaks can become a potential threat to global public health, as it became the source for the subsequent transmission events in Spain and the USA. The urgent need for rapid and affordable means of detecting Ebola is crucial to control the spread of EVD and prevent devastating fatalities. Current diagnostic techniques include molecular diagnostics and other serological and antigen detection assays; which can be time-consuming, laboratory-based, often require trained personnel and specialized equipment. In this review, we discuss the various Ebola detection techniques currently in use, and highlight the potential future directions pertinent to the development and adoption of novel point-of-care diagnostic tools. Finally, a case is made for the need to develop novel microfluidic technologies and versatile rapid detection platforms for early detection of EVD. PMID:28440096

A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

PubMed Central

Wesseling, Hendrik; Chan, Man K; Tsang, T M; Ernst, Agnes; Peters, Fabian; Guest, Paul C; Holmes, Elaine; Bahn, Sabine

2013-01-01

Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass spectrometry proteomic- and proton nuclear magnetic resonance-based metabonomic profiling of the rat frontal cortex after chronic phencyclidine (PCP) intervention, which induces SCZ-like symptoms. The findings were compared with results from a proteomic profiling of post-mortem prefrontal cortex from SCZ patients and with relevant findings in the literature. Through this approach, we identified proteomic alterations in glutamate-mediated Ca2+ signaling (Ca2+/calmodulin-dependent protein kinase II, PPP3CA, and VISL1), mitochondrial function (GOT2 and PKLR), and cytoskeletal remodeling (ARP3). Metabonomic profiling revealed changes in the levels of glutamate, glutamine, glycine, pyruvate, and the Ca2+ regulator taurine. Effects on similar pathways were also identified in the prefrontal cortex tissue from human SCZ subjects. The discovery of similar but not identical proteomic and metabonomic alterations in the chronic PCP rat model and human brain indicates that this model recapitulates only some of the molecular alterations of the disease. This knowledge may be helpful in understanding mechanisms underlying psychosis, which, in turn, can facilitate improved therapy and drug discovery for SCZ and other psychiatric diseases. Most importantly, these molecular findings suggest that the combined use of multiple models may be required for more effective translation to studies of human SCZ. PMID:23942359

Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure

PubMed Central

Jonasson, Sara; Eriksson, Johan; Berntzon, Lotta; Spáčil, Zdenĕk; Ilag, Leopold L.; Ronnevi, Lars-Olof; Rasmussen, Ulla; Bergman, Birgitta

2010-01-01

β-methylamino-L-alanine (BMAA), a neurotoxic nonprotein amino acid produced by most cyanobacteria, has been proposed to be the causative agent of devastating neurodegenerative diseases on the island of Guam in the Pacific Ocean. Because cyanobacteria are widespread globally, we hypothesized that BMAA might occur and bioaccumulate in other ecosystems. Here we demonstrate, based on a recently developed extraction and HPLC-MS/MS method and long-term monitoring of BMAA in cyanobacterial populations of a temperate aquatic ecosystem (Baltic Sea, 2007–2008), that BMAA is biosynthesized by cyanobacterial genera dominating the massive surface blooms of this water body. BMAA also was found at higher concentrations in organisms of higher trophic levels that directly or indirectly feed on cyanobacteria, such as zooplankton and various vertebrates (fish) and invertebrates (mussels, oysters). Pelagic and benthic fish species used for human consumption were included. The highest BMAA levels were detected in the muscle and brain of bottom-dwelling fishes. The discovery of regular biosynthesis of the neurotoxin BMAA in a large temperate aquatic ecosystem combined with its possible transfer and bioaccumulation within major food webs, some ending in human consumption, is alarming and requires attention. PMID:20439734

Preclinical Corrective Gene Transfer in Xeroderma Pigmentosum Human Skin Stem Cells

PubMed Central

Warrick, Emilie; Garcia, Marta; Chagnoleau, Corinne; Chevallier, Odile; Bergoglio, Valérie; Sartori, Daniela; Mavilio, Fulvio; Angulo, Jaime F; Avril, Marie-Françoise; Sarasin, Alain; Larcher, Fernando; Del Rio, Marcela; Bernerd, Françoise; Magnaldo, Thierry

2012-01-01

Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (>1040 cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients. PMID:22068429

Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis.

PubMed

Weaver, Lehn K; Behrens, Edward M

2017-03-01

Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remains for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.

Pharmabiotic Manipulation of the Microbiota in Gastrointestinal Disorders: A Clinical Perspective.

PubMed

Giron, Fanny; Quigley, Eamonn M M

2018-04-24

The advent and widespread availability of high-throughput technology has revolutionized the assessment of the communities of microorganisms that inhabit the gastrointestinal tract - the gut microbiota. As our understanding of the role of the microbiota in health and human disease increases so to do efforts to prevent and treat disease through the modulation of the microbiota. Several strategies are available to us and range from time honored approaches, such as antibiotics and probiotics, to changes in diet, the administration of prebiotics as food supplements and fecal microbiota transplantation. Of these, diet is perhaps the most pervasive but often ignored modulator of the microbiota and a failure to recognize its impact complicates the interpretation of many microbiota studies. The impacts of antibiotics on the microbiotia are more complex than originally thought and, though antibiotics can be life-saving, their effects on commensal bacterial populations can have devastating consequences. Though there have been many studies of, and even more claims made for, probiotics, the majority of available studies suffer from significant deficits in study design and execution and many claims remain to be substantiated. Though holding much promise, the study of prebiotics in human disease is still in its infancy. Possibilities other than the administration of live organisms have been identified through efforts to mine the microbiota for novel therapeutics and include dead organisms, bacterial components, small molecules elaborated by bacteria and even bacterial DNA; the term pharmabiotic has been introduced to encompass the full range of therapeutic possibilities that the microbiota offers.

Translational Model of Zika Virus Disease in Baboons.

PubMed

Gurung, Sunam; Preno, Alisha N; Dubaut, Jamie P; Nadeau, Hugh; Hyatt, Kimberly; Reuter, Nicole; Nehete, Bharti; Wolf, Roman F; Nehete, Pramod; Dittmer, Dirk P; Myers, Dean A; Papin, James F

2018-06-06

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus with devastating outcomes seen recently in the Americas due to the association of maternal ZIKV infection with fetal microcephaly and other fetal malformations not previously associated with flavivirus infections. Here, we have developed the olive baboon ( Papio anubis ) as a non-human primate (NHP) translational model for the study of ZIKV pathogenesis and associated disease outcomes to contrast and compare with humans and other major NHPs such as macaques. Following subcutaneous inoculation of adult male and non-pregnant female baboons, viremia was detected at 3 and 4 days post infection (dpi) with the concordant presentation of a visible rash and conjunctivitis similar to human ZIKV infection. Furthermore, virus was detected in the mucosa and cerebrospinal fluid. A robust ZIKV-specific IgM and IgG antibody response was also observed in all animals. These data show striking similarity between humans and the olive baboon following infection with ZIKV suggesting our model as a suitable translational NHP model to study ZIKV pathogenesis and potential therapeutics. IMPORTANCE ZIKV was first identified in 1947 in a sentinel rhesus monkey in Uganda and subsequently spread to Southeast Asia. Until 2007, only a small number of cases were reported, and ZIKV infection was relatively minor until the South Pacific and Brazilian outbreaks where more severe outcomes were reported. Here we present the baboon as a non-human primate model for contrast and comparison to other published animal models of ZIKV such as the mouse and macaque species. Baboons breed year around and are not currently a primary non-human primate species used in biomedical research marking them more readily available for studies other than Human Immunodeficiency virus studies, which many macaque species are designated for. This taken together with the similarities baboons have with humans, such as immunology, reproduction, genetics and size, makes the baboon an attractive NHP model for ZIKV studies in comparison to other non-human primates. Copyright © 2018 American Society for Microbiology.

The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon

PubMed Central

Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K.; Alcami, Antonio

2010-01-01

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. PMID:20019241

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

PubMed Central

Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X.-Q.; Beitel, Lenore K.; Durcan, Thomas M.

2018-01-01

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders. PMID:29467610

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders.

PubMed

Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X-Q; Beitel, Lenore K; Durcan, Thomas M

2018-01-01

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop "first-of-their-kind" disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an "Open Science" model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

Recent advances in the development of vaccines for Ebola virus disease.

PubMed

Ohimain, Elijah Ige

2016-01-04

Ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. Ebola virus (EBOV) is a zoonotic infection, which emerges and re-emerges in human populations. The 2014 outbreak was caused by the Zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. The 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. It is the first time that the virus was sustained in urban centers and spread beyond Africa into Europe and USA. Thus far, over 22,000 cases have been reported with about 50% mortality in one year. There are currently no approved therapeutics and preventive vaccines against Ebola virus disease (EVD). Responding to the devastating effe1cts of the 2014 outbreak and the potential risk of global spread, has spurred research for the development of therapeutics and vaccines. This review is therefore aimed at presenting the progress of vaccine development. Results showed that conventional inactivated vaccines produced from EBOV by heat, formalin or gamma irradiation appear to be ineffective. However, novel vaccines production techniques have emerged leading to the production of candidate vaccines that have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models. Some of the promising vaccines have undergone phase 1 clinical trials, which demonstrated their safety and immunogenicity. Many of the candidate vaccines are vector based such as Vesicular Stomatitis Virus (VSV), Rabies Virus (RABV), Adenovirus (Ad), Modified Vaccinia Ankara (MVA), Cytomegalovirus (CMV), human parainfluenza virus type 3 (HPIV3) and Venezuelan Equine Encephalitis Virus (VEEV). Other platforms include virus like particle (VLP), DNA and subunit vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia.

PubMed

Fukawa, Tomoya; Yan-Jiang, Benjamin Chua; Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Huang, Dan; Qian, Chao-Nan; Ong, Pauline; Li, Zhimei; Chen, Shuwen; Mak, Shi Ya; Lim, Wan Jun; Kanayama, Hiro-Omi; Mohan, Rosmin Elsa; Wang, Ruiqi Rachel; Lai, Jiunn Herng; Chua, Clarinda; Ong, Hock Soo; Tan, Ker-Kan; Ho, Ying Swan; Tan, Iain Beehuat; Teh, Bin Tean; Shyh-Chang, Ng

2016-06-01

Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer. Additionally, although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid-induced oxidative stress could be targeted to prevent cancer-induced cachexia.

New insights into pancreatic cancer biology.

PubMed

Hidalgo, M

2012-09-01

Pancreatic cancer remains a devastating disease. Over the last few years, there have been important advances in the molecular and biological understanding of pancreatic cancer. This included understanding of the genomic complexity of the disease, the role of pancreatic cancer stem cells, the relevance of the tumor microenvironment, and the unique metabolic adaptation of pancreas cancer cells to obtain nutrients under hypoxic environment. In this paper, we review the most salient developments in these few areas.

Falling Behind. An Examination of Critical Social Programs and Policies in New York State. Implications for the Black Community. Report of the Human Services Subcommittee. The Governor's Advisory Committee for Black Affairs. Volume 2, Human Services.

ERIC Educational Resources Information Center

New York Governor's Advisory Committee for Black Affairs, Albany.

This document, examining critical social programs and policies impacting blacks in New York State, is the second volume of a study of the needs of the more than two million blacks in New York. The following human service issues that have a devastating impact on the black community and threaten its long-term viability are discussed: (1) Acquired…

Johnsongrass mosaic virus contributes to maize lethal necrosis in East Africa

USDA-ARS?s Scientific Manuscript database

Maize lethal necrosis (MLN), a severe virus disease of maize, has emerged in East Africa in recent years with devastating effects on production and food security where maize is a staple subsistence crop. In extensive surveys of MLN-symptomatic plants in East Africa, sequences of Johnsongrass mosaic ...

Effects of elevated [CO2] on the defense response of wheat against Fusarium graminearum infection

USDA-ARS?s Scientific Manuscript database

Fusarium head blight (FHB) is one of the world’s most devastating wheat diseases, and results in significant yield loss and contamination of grain with harmful mycotoxins called trichothecenes. Despite emerging risks of increased mycotoxin contamination in food and feed associated with climate chang...

Partial proteome of the corynetoxin-producing Gram-positive bacterium, Rathayibacter toxicus

USDA-ARS?s Scientific Manuscript database

Rathayibacter toxicus is a Gram-positive bacterium that is the causative agent of annual ryegrass toxicity (ARGT), a disease that causes devastating losses in the Australian livestock industry. R. toxicus exhibits a complex life cycle, using the nematode Anguina funesta as a physical vector to carry...

CNV analysis of host responses to porcine reproductive and respiratory syndrome virus infection

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease with a significant impact on the swine industry causing major economic losses. Recent studies revealed a region on Sus Scrofa chromosome (SSC) 4 associated with serum viremia and weight gain in pigs infected with the PRRS ...

Current state of knowledge of hepatic encephalopathy (part IV): Management of Hepatic Encephalopathy by liver support systems.

PubMed

Hassanein, Tarek

2017-04-01

Hepatic Encephalopathy is a devastating complication of End-Stage Liver Disease. In its severe grades it requires extra intervention beyond the standard medical approaches. In this article were view the role of liver support systems in managing hepatic encephalopthy.

Structural and Functional Characterization of TRI3 Acetyltransferase from Fusarium sporotrichioides

USDA-ARS?s Scientific Manuscript database

Fusarium Head Blight (FHB) is a devastating disease of cereal crops whose worldwide incidence is increasing and at present there is no satisfactory way of combating this pathogen or its associated toxins. There is a wide variety of trichothecene mycotoxins and they all contain a 12,13-epoxytrichoth...

Empirical, metagenomic, and computational techniques illuminate the mechanisms by which fungicides compromise bee health

USDA-ARS?s Scientific Manuscript database

Because disease can be devastating to crops, growers often spray fungicides as preventative measures. Unfortunately, many sprays are applied to in-bloom crops, which expose bees to fungicide residues. Generally considered “bee-safe,” fungicides are applied globally on flowering crops. However, there...

Marker validation for Rpf1 red stele resistance in strawberry

USDA-ARS?s Scientific Manuscript database

Red stele is a devastating root rot disease in strawberries. Several sources for genetic resistance are exploited in breeding, and several race-specific R-genes were identified. Recently, a tightly linked SSR marker was found for the Rpf1 gene at Wageningen-UR, The Netherlands. One hundred and forty...

Controlled release of Pantoea agglomerans E325 for biocontrol of fire blight

USDA-ARS?s Scientific Manuscript database

Microencapsulation and controlled release of Pantoea agglomerans strain E325 (E325), which is an antagonist to bacterial pathogen (Erwinia amylovora) of fire blight, a devastating disease of apple and pear, have been investigated. Uniform core-shell alginate microcapsules (AMCs), 60-300 µm in diamet...

Host plant resistance associated with Poncirus trifoliata influences oviposition, development and adult emergence of Diaphorina citri (Hemiptera: Liviidae)

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid, Diaphorina citri Kuwayama, is the primary vector of the phloem-inhabiting bacterium Candidatus Liberibacter asiaticus putatively responsible for citrus greening (huanglongbing), a devastating citrus disease. Infestations of Diaphorina citri frequently develop on Citrus and ...

Current Agricultural Research Issues on One-Host ticks and Bovine Babesiosis

USDA-ARS?s Scientific Manuscript database

Bovine babesiosis is a tick-borne disease caused by the apicomplexan protozoans Babesia bovis and B. bigemina, which can have devastating economic effects on the livestock industry. Estimates indicate the domestic livestock industry realizes annual savings of at least 3 billion dollars at today’s c...

Allelic analysis of sheath blight resistance with association mapping in rice

USDA-ARS?s Scientific Manuscript database

Sheath blight is one of the most devastating diseases world-wide in rice. For the first time, we adopted association mapping to identify quantitative trait loci for sheath blight resistance from the USDA rice mini-core collection. The phenotyping was conducted with a newly developed micro-chamber me...

Transgenic wheat expressing a barley UDP-glucosyltransferase detoxifies deoxynivalenol and provides high levels of resistance to Fusarium graminearum

USDA-ARS?s Scientific Manuscript database

Fusarium head blight (FHB), mainly caused by Fusarium graminearum, is a devastating disease of wheat and barley that results in huge economic losses worldwide. During infection, F. graminearum produces trichothecene mycotoxins, such as deoxynivalenol (DON), that increase fungal virulence and decreas...

Future Approaches for Inner Ear Protection and Repair

ERIC Educational Resources Information Center

Shibata, Seiji B.; Raphael, Yehoash

2010-01-01

Health care professionals tending to patients with inner ear disease face inquiries about therapy options, including treatments that are being developed for future use but not yet available. The devastating outcome of sensorineural hearing loss, combined with the permanent nature of the symptoms, make these inquiries demanding and frequent. The…

Protecting the Oblivious

ERIC Educational Resources Information Center

Ramaswami, Rama

2008-01-01

When it comes to dealing with cyber attacks, there's no silver bullet. Ironically, however, college educators are already accustomed to wielding what may be the best weapon of all--education. Assaulted by the myriad species of spam, worms, Trojan horses, spyware, viruses, and other diseases that so easily infect and sometimes devastate campus…

A graft-based chemotherapy method for screening effective molecules and rescuing Huanglongbing (HLB)-affected citrus plants

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB), the most devastating disease of citrus worldwide, is associated with three species of fastidious and phloem-limited a-Proteobacteria in the genus of ‘Candidatus Liberibacter’. We previously reported a regeneration-based chemical screening system using periwinkle cuttings. In ...

SNP-based differentiation of Phytophthora infestans clonal lineages using locked nucleic acid probes and high resolution melt analysis

USDA-ARS?s Scientific Manuscript database

Phytophthora infestans, the cause of the devastating late blight disease of potato and tomato, exhibits a clonal reproductive lifestyle in North America. Phenotypes such as fungicide sensitivity and host preference are conserved among individuals within clonal lineages, while substantial phenotypic ...

Colonization of Clonostachys rosea on soybean root inoculated with Fusarium graminearum

USDA-ARS?s Scientific Manuscript database

Soybean root rot, caused by Fusarium graminearum, is a devastating disease. Clonostachys rosea has been reported to have protection against plant pathogens in different crops. The objectives of this study were to determine if a strain of C. rosea (ACM941) can colonize soybean root that were inocula...

Asian citrus psyllid, huanglongbing and the orange jasmine conundrum

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid (ACP) is an important invasive pest in Florida because it vectors a bacterium ‘Ca. Liberibacter asiaticus’ (LAS) responsible for a devastating citrus disease known as huanglongbing (HLB). Soon after finding HLB in Florida, concerns arose that orange jasmine in urban areas wo...

Submission of nucleotide sequence eimeria tenella elongation factor 1-alpha to genBank database

USDA-ARS?s Scientific Manuscript database

Avian coccidiosis is caused by multiple species of the apicomplexan protozoan, Eimeria, and is one of the most economically devastating enteric diseases for the poultry industry worldwide. Host immunity to Eimeria infection, however, is relatively species-specific. The ability to immunize chickens a...

The Socioeconomic Impact of Lymphatic Filariasis in Tropical Countries

ERIC Educational Resources Information Center

Nwoke, Bertram Ekejiuba Bright; Nwoke, Eunice Anyalewechi; Dozie, Ikechukwu Nosike Simplicius

2007-01-01

Lymphatic filariasis (LF) is an endemic parasitic disease and a major cause of acute and chronic morbidity and incapacitation with devastating public health and socio-economic consequences. It exacerbates poor conditions of afflicted persons and endemic communities through reduced or lost labour supply and productivity. Stigmatisation and…

First report of Xyleborus glabratus (Coleoptera: Curculionidae: Scolytinae) and laurel wilt in Louisiana, USA: The disease continues westward on sassafras

Treesearch

Stephen W. Fraedrich; C. Wood Johnson; Roger D. Menard; Thomas C. Harrington; Rabiu Olatinwo; G. Susan Best

2015-01-01

Laurel wilt, caused by Raffaelea lauricola Harrington, Fraedrich & Aghayeva (Ophiostomatales: Ophiostomataceae), has spread rapidly through the coastal plains forests of the southeastern United States (USA) with devastating effects on redbay (Persea borbonia [L.] Spreng.; Laurales: Lauraceae) populations (Fraedrich et...

Host-choice behavior of Diaphorina citri Kuwayama (Hemiptera: Psyllidae) under laboratory conditions

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the vector of huanglongbing (HLB), considered to be the most devastating disease of citrus worldwide. Knowledge of the ACP’s host-plant finding behavior aids in our understanding of the epidemiology of HLB and in designing experiments to ...

Huanglongbing increases Diplodia Stem End Rot in Citrus sinensis

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB), one of the most devastating diseases of citrus is caused by the a-Proteobacteria Candidatus Liberibacter. Diplodia natalensis Pole-Evans is a fungal pathogen which has been known to cause a postharvest stem-end rot of citrus, the pathogen infects citrus fruit under the calyx, an...

Speech Intelligibility and Marital Communication in Amyotrophic Lateral Sclerosis: An Exploratory Study

ERIC Educational Resources Information Center

Joubert, Karin; Bornman, Juan; Alant, Erna

2011-01-01

Amyotrophic lateral sclerosis (ALS), a rapidly progressive neuromuscular disease, has a devastating impact not only on individuals diagnosed with ALS but also their spouses. Speech intelligibility, often compromised as a result of dysarthria, affects the couple's ability to maintain effective, intimate communication. The purpose of this…

Morphological characterization of a new and easily recognizable nuclear male sterile mutant of sorghum (Sorghum bicolor).

USDA-ARS?s Scientific Manuscript database

All commercial sorghum (Sorghum bicolor L. Moench) hybrids are produced using A1 cytoplasmic male sterility (CMS) lines. However, this homogenous cytoplasm could predispose sorghum to devastating diseases. Furthermore, it is expensive to develop and maintain the CMS-based breeding system, because it...

Multimodal cues drive host-plant assessment in Asian citrus psyllid (Diaphorina citri)

USDA-ARS?s Scientific Manuscript database

Asian citrus psyllid (Diaphorina citri) transmits the causal agent of Huanglongbing, a devastating disease of citrus trees. In this study, we measured behavioral responses of D. citri to combinations of visual, olfactory, and gustatory stimuli in test arenas. Stimuli were presented to the psyllids ...

Spectral difference analysis and airborne imaging classification for citrus greening infected trees

USDA-ARS?s Scientific Manuscript database

Citrus greening, also called Huanglongbing (HLB), became a devastating disease spread through citrus groves in Florida, since it was first found in 2005. Multispectral (MS) and hyperspectral (HS) airborne images of citrus groves in Florida were acquired to detect citrus greening infected trees in 20...

Within-orchard edge effects of the azimuth of the sun on Diaphorina citri adults in mature orchards

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) has been considered the most devastating disease of citrus. The bacterium and vector associated with HLB in Florida are ‘Candidatus Liberibacter asiaticus’ and Diaphorina citri (Asian citrus psyllid), respectively. D. citri is positively phototropic, and higher populations have b...

Human health risk assessment due to global warming--a case study of the Gulf countries.

PubMed

Husain, Tahir; Chaudhary, Junaid Rafi

2008-12-01

Accelerated global warming is predicted by the Intergovernmental Panel on Climatic Change (IPCC) due to increasing anthropogenic greenhouse gas emissions. The climate changes are anticipated to have a long-term impact on human health, marine and terrestrial ecosystems, water resources and vegetation. Due to rising sea levels, low lying coastal regions will be flooded, farmlands will be threatened and scarcity of fresh water resources will be aggravated. This will in turn cause increased human suffering in different parts of the world. Spread of disease vectors will contribute towards high mortality, along with the heat related deaths. Arid and hot climatic regions will face devastating effects risking survival of the fragile plant species, wild animals, and other desert ecosystems. The paper presents future changes in temperature, precipitation and humidity and their direct and indirect potential impacts on human health in the coastal regions of the Gulf countries including Yemen, Oman, United Arab Emirates, Qatar, and Bahrain. The analysis is based on the long-term changes in the values of temperature, precipitation and humidity as predicted by the global climatic simulation models under different scenarios of GHG emission levels. Monthly data on temperature, precipitation, and humidity were retrieved from IPCC databases for longitude 41.25 degrees E to 61.875 degrees E and latitude 9.278 degrees N to 27.833 degrees N. Using an average of 1970 to 2000 values as baseline, the changes in the humidity, temperature and precipitation were predicted for the period 2020 to 2050 and 2070 to 2099. Based on epidemiological studies on various diseases associated with the change in temperature, humidity and precipitation in arid and hot regions, empirical models were developed to assess human health risk in the Gulf region to predict elevated levels of diseases and mortality rates under different emission scenarios as developed by the IPCC.The preliminary assessment indicates increased mortality rates due to cardiovascular and respiratory illnesses, thermal stress, and increased frequency of infectious vector borne diseases in the region between 2070 and 2099.

Small RNA profiling reveals phosphorus deficiency as a contributing factor in symptom expression for citrus huanglongbing disease.

PubMed

Zhao, Hongwei; Sun, Ruobai; Albrecht, Ute; Padmanabhan, Chellappan; Wang, Airong; Coffey, Michael D; Girke, Thomas; Wang, Zonghua; Close, Timothy J; Roose, Mikeal; Yokomi, Raymond K; Folimonova, Svetlana; Vidalakis, Georgios; Rouse, Robert; Bowman, Kim D; Jin, Hailing

2013-03-01

Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus 'Candidatus Liberibacter' (Ca. L.). Powerful diagnostic tools and management strategies are desired to control HLB. Host small RNAs (sRNA) play a vital role in regulating host responses to pathogen infection and are used as early diagnostic markers for many human diseases, including cancers. To determine whether citrus sRNAs regulate host responses to HLB, sRNAs were profiled from Citrus sinensis 10 and 14 weeks post grafting with Ca. L. asiaticus (Las)-positive or healthy tissue. Ten new microRNAs (miRNAs), 76 conserved miRNAs, and many small interfering RNAs (siRNAs) were discovered. Several miRNAs and siRNAs were highly induced by Las infection, and can be potentially developed into early diagnosis markers of HLB. miR399, which is induced by phosphorus starvation in other plant species, was induced specifically by infection of Las but not Spiroplasma citri that causes citrus stubborn-a disease with symptoms similar to HLB. We found a 35% reduction of phosphorus in Las-positive citrus trees compared to healthy trees. Applying phosphorus oxyanion solutions to HLB-positive sweet orange trees reduced HLB symptom severity and significantly improved fruit production during a 3-year field trial in south-west Florida. Our molecular, physiological, and field data suggest that phosphorus deficiency is linked to HLB disease symptomology.

ADAM10 Missense Mutations Potentiate β-Amyloid Accumulation by Impairing Prodomain Chaperone Function

PubMed Central

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M.; Gannon, Moira A.; Lesinski, Andrea N.; Kim, Doo Yeon; Tanzi, Rudolph E.

2014-01-01

SUMMARY The generation of Aβ, the main component of senile plaques in Alzheimer’s disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that co-segregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. PMID:24055016

ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function.

PubMed

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M; Gannon, Moira A; Lesinski, Andrea N; Kim, Doo Yeon; Tanzi, Rudolph E

2013-10-16

The generation of Aβ, the main component of senile plaques in Alzheimer's disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that cosegregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Batrachochytrium salamandrivorans and the risk of a second amphibian pandemic

USGS Publications Warehouse

Yap, Tiffany A.; Nguyen, Natalie T.; Serr, Megan; Shepak, Alex; Vredenburg, Vance

2017-01-01

Amphibians are experiencing devastating population declines globally. A major driver is chytridiomycosis, an emerging infectious disease caused by the fungal pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). Bdwas described in 1999 and has been linked with declines since the 1970s, while Bsal is a more recently discovered pathogen that was described in 2013. It is hypothesized that Bsaloriginated in Asia and spread via international trade to Europe, where it has been linked to salamander die-offs. Trade in live amphibians thus represents a significant threat to global biodiversity in amphibians. We review the current state of knowledge regarding Bsal and describe the risk of Bsal spread. We discuss regional responses to Bsal and barriers that impede a rapid, coordinated global effort. The discovery of a second deadly emerging chytrid fungal pathogen in amphibians poses an opportunity for scientists, conservationists, and governments to improve global biosecurity and further protect humans and wildlife from a growing number of emerging infectious diseases.

Current methods of laboratory diagnosis of Chlamydia trachomatis infections.

PubMed Central

Black, C M

1997-01-01

Infections caused by Chlamydia trachomatis are probably the most common sexually transmitted diseases in the United States. Commonly unrecognized and often inadequately treated, chlamydial infections can ascend the reproductive tract and cause pelvic inflammatory disease, which often results in the devastating consequences of infertility, ectopic pregnancy, or chronic pelvic pain. C. trachomatis infections are also known to increase the risk for human immunodeficiency virus infection. The obligate intracellular life cycle of C. trachomatis has traditionally required laboratory diagnostic tests that are technically demanding, labor-intensive, expensive, and difficult to access. In spite of these historical challenges, however, laboratory diagnosis of C. trachomatis has been a rapidly advancing area in which there is presently a wide array of commercial diagnostic technologies, costs, manufacturers. This review describes and compares the diagnostic methods for C. trachomatis infection that are currently approved for use in the United States, including the newest DNA amplification technologies which are yet to be licensed for commercial use. Issues to consider in selecting a test for purposes of screening versus diagnosis based on prevalence, performance, legal, social, and cost issues are also discussed. PMID:8993862

Toward development of a surface-enhanced Raman scattering (SERS)-based cancer diagnostic immunoassay panel.

PubMed

Granger, Jennifer H; Granger, Michael C; Firpo, Matthew A; Mulvihill, Sean J; Porter, Marc D

2013-01-21

Proteomic analyses of readily obtained human fluids (e.g., serum, urine, and saliva) indicate that the diagnosis of complex diseases will be enhanced by the simultaneous measurement of multiple biomarkers from such samples. This paper describes the development of a nanoparticle-based multiplexed platform that has the potential for simultaneous read-out of large numbers of biomolecules. For this purpose, we have chosen pancreatic adenocarcinoma (PA) as a test bed for diagnosis and prognosis. PA is a devastating form of cancer in which an estimated 86% of diagnoses resulted in death in the United States in 2010. The high mortality rate is due, in part, to the asymptomatic development of the disease and the dearth of sensitive diagnostics available for early detection. One promising route lies in the development of a serum biomarker panel that can generate a signature unique to early stage PA. We describe the design and development of a proof-of-concept PA biomarker immunoassay array coupled with surface-enhanced Raman scattering (SERS) as a sensitive readout method.

Intraspinal Stem Cell Transplantation for Amyotrophic Lateral Sclerosis

PubMed Central

Chen, Kevin S.; Sakowski, Stacey A.; Feldman, Eva L.

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder in which the loss of upper and lower motor neurons produces progressive weakness and eventually death. In the decades since the approval of riluzole, the only FDA approved medication to moderately slow progression of ALS, no new therapeutics have arisen to alter the course of the disease. This is partly due to our incomplete understanding of the complex pathogenesis of motor neuron degeneration. Stem cells have emerged as an attractive option in treating ALS since they come armed with equally complex cellular machinery and may modulate the local microenvironment in many ways to rescue diseased motor neurons. While various stem cell types are being evaluated in preclinical and early clinical applications, here we review the preclinical strategies and advances supporting the recent clinical translation of neural progenitor cell therapy for ALS. Specifically, we focus on the use of spinal cord neural progenitor cells and the pipeline starting from preclinical studies to the designs of the Phase I and IIa clinical trials involving direct intraspinal transplantation in humans. PMID:26696091

The impact of contact

NASA Astrophysics Data System (ADS)

Finney, B.

1986-10-01

Scenarios of the impact on human society of radio contact with an extraterrestrial civilization are presented. Some believe that contact with advanced extraterrestrials would quickly devastate the human spirit, while others believe that these super-intelligent beings would show the inhabitants of the earth how to live in peace. It is proposed that the possible existence of extraterrestrial civilizations and the development of means of studying and communicating with them need to be considered.

White-nose syndrome in North American bats - U.S. Geological Survey updates

USGS Publications Warehouse

Lankau, Emily W.; Moede Rogall, Gail

2016-12-27

White-nose syndrome is a devastating wildlife disease that has killed millions of hibernating bats. This disease first appeared in New York during 2007 and has continued to spread at an alarming rate from the northeastern to the central United States and throughout eastern Canada. The disease is named for the fungus Pseudogymnoascus destructans, which often appears white when it infects the skin of the nose, ears, and wings of hibernating bats. This fact sheet provides updates on white-nose syndrome research and management efforts and highlights US Geological Survey scientists’ contributions to understanding and combating this disease.

Childhood inflammatory brain diseases: pathogenesis, diagnosis and therapy.

PubMed

Twilt, Marinka; Benseler, Susanne M

2014-08-01

Inflammatory brain diseases (IBrainDs) are a leading cause of devastating neurological deficits or neuropsychiatric syndromes in previously healthy children. The spectrum is expanding rapidly and new disease entities have been discovered in the last decade. IBrainD can occur as a primary disease or may occur secondary to an underlying cause. This review focuses on the clinical presentation, diagnostic features, pathology and histology characteristics and treatment of the primary childhood IBrainDs. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multiple sclerosis.

PubMed

Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

2015-06-01

Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS. Copyright © 2015 Elsevier Inc. All rights reserved.

Lifeboat Ethics: A Reply to Hardin

ERIC Educational Resources Information Center

Besecker, Janet; Elder, Phil

1975-01-01

This paper is a rebuttal to Garrett Hardin's thesis that long-term survival of human beings can be threatened by environmental devastation caused by brief humanitarian desires to save lives. Discussions include population dynamics, resource distribution, ecological stability, and ethics of developed nations and undeveloped nations relationships.…

Chemical analysis of plants that poison livestock: Successes, challenges, and opportunities

USDA-ARS?s Scientific Manuscript database

Poisonous plants have a devastating impact on the livestock industry, as well as human health. In order to fully understand the effects of poisonous plants, multiple scientific disciplines are required. Chemical analysis of plant secondary compounds is key to identifying the responsible toxins, char...

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

PubMed

Mohammadi, Alireza; Maleki-Jamshid, Ali; Sanooghi, Davood; Milan, Peiman Brouki; Rahmani, Arash; Sefat, Farshid; Shahpasand, Koorosh; Soleimani, Mansoureh; Bakhtiari, Mehrdad; Belali, Rafie; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Perry, George; Mozafari, Masoud

2018-03-16

A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

Psychiatric and Psychological Impact of Chronic Skin Disease.

PubMed

Jafferany, Mohammad; Pastolero, Paul

2018-04-26

Chronic skin disease has a devastating effect on a person's physical and psychological well-being. Skin disease significantly impacts all aspects of a patient's life including school, relationships, career choices, social and leisure activities, and sexual life. The physical, psychological, and social consequences affect not only the patients, but also caregivers and family members as well. Common psychological problems associated with skin disease include, but are not limited to, feelings of stress, anxiety, anger, depression, shame, social isolation, low self-esteem, and embarrassment. Besides psychopharmacology, multiple psychotherapeutic techniques have proved to be helpful in addressing the psychological sequelae of skin disease. © Copyright 2018 Physicians Postgraduate Press, Inc.

Seeking approval: Present and future therapies for pemphigus vulgaris

PubMed Central

Mao, Xuming; Payne, Aimee S

2014-01-01

Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes. Despite the potentially fatal prognosis, there are currently no FDA-approved treatments specifically for pemphigus. In 2006, the FDA designated orphan drug status to mycophenolate mofetil for the treatment of pemphigus vulgaris indicating both federal and commercial interest in developing therapies for this devastating disease. This review focuses on pemphigus therapies that are currently in preclinical or clinical trials, as well as potential novel therapies based on recent advances in the understanding of the pathophysiology of this disease. PMID:18465660

Seeking approval: present and future therapies for pemphigus vulgaris.

PubMed

Mao, Xuming; Payne, Aimee S

2008-05-01

Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes. Despite the potentially fatal prognosis, there are currently no FDA-approved treatments specifically for pemphigus. In 2006, the FDA designated orphan drug status to mycophenolate mofetil for the treatment of pemphigus vulgaris, indicating both federal and commercial interest in developing therapies for this devastating disease. This review focuses on pemphigus therapies that are currently in preclinical or clinical trials, as well as potential novel therapies based on recent advances in the understanding of the pathophysiology of this disease.

Creation of Rift Valley Fever Viruses with Four-Segmented Genomes Reveals Flexibility in Bunyavirus Genome Packaging

PubMed Central

Oreshkova, Nadia; Moormann, Rob J. M.; Kortekaas, Jeroen

2014-01-01

ABSTRACT Bunyavirus genomes comprise a small (S), a medium (M), and a large (L) RNA segment of negative polarity. Although the untranslated regions have been shown to comprise signals required for transcription, replication, and encapsidation, the mechanisms that drive the packaging of at least one S, M, and L segment into a single virion to generate infectious virus are largely unknown. One of the most important members of the Bunyaviridae family that causes devastating disease in ruminants and occasionally humans is the Rift Valley fever virus (RVFV). We studied the flexibility of RVFV genome packaging by splitting the glycoprotein precursor gene, encoding the (NSm)GnGc polyprotein, into two individual genes encoding either (NSm)Gn or Gc. Using reverse genetics, six viruses with a segmented glycoprotein precursor gene were rescued, varying from a virus comprising two S-type segments in the absence of an M-type segment to a virus consisting of four segments (RVFV-4s), of which three are M-type. Despite that all virus variants were able to grow in mammalian cell lines, they were unable to spread efficiently in cells of mosquito origin. Moreover, in vivo studies demonstrated that RVFV-4s is unable to cause disseminated infection and disease in mice, even in the presence of the main virulence factor NSs, but induced a protective immune response against a lethal challenge with wild-type virus. In summary, splitting bunyavirus glycoprotein precursor genes provides new opportunities to study bunyavirus genome packaging and offers new methods to develop next-generation live-attenuated bunyavirus vaccines. IMPORTANCE Rift Valley fever virus (RVFV) causes devastating disease in ruminants and occasionally humans. Virions capable of productive infection comprise at least one copy of the small (S), medium (M), and large (L) RNA genome segments. The M segment encodes a glycoprotein precursor (GPC) protein that is cotranslationally cleaved into Gn and Gc, which are required for virus entry and fusion. We studied the flexibility of RVFV genome packaging and developed experimental live-attenuated vaccines by applying a unique strategy based on the splitting of the GnGc open reading frame. Several RVFV variants, varying from viruses comprising two S-type segments to viruses consisting of four segments (RVFV-4s), of which three are M-type, could be rescued and were shown to induce a rapid protective immune response. Altogether, the segmentation of bunyavirus GPCs provides a new method for studying bunyavirus genome packaging and facilitates the development of novel live-attenuated bunyavirus vaccines. PMID:25008937

Creation of Rift Valley fever viruses with four-segmented genomes reveals flexibility in bunyavirus genome packaging.

PubMed

Wichgers Schreur, Paul J; Oreshkova, Nadia; Moormann, Rob J M; Kortekaas, Jeroen

2014-09-01

Bunyavirus genomes comprise a small (S), a medium (M), and a large (L) RNA segment of negative polarity. Although the untranslated regions have been shown to comprise signals required for transcription, replication, and encapsidation, the mechanisms that drive the packaging of at least one S, M, and L segment into a single virion to generate infectious virus are largely unknown. One of the most important members of the Bunyaviridae family that causes devastating disease in ruminants and occasionally humans is the Rift Valley fever virus (RVFV). We studied the flexibility of RVFV genome packaging by splitting the glycoprotein precursor gene, encoding the (NSm)GnGc polyprotein, into two individual genes encoding either (NSm)Gn or Gc. Using reverse genetics, six viruses with a segmented glycoprotein precursor gene were rescued, varying from a virus comprising two S-type segments in the absence of an M-type segment to a virus consisting of four segments (RVFV-4s), of which three are M-type. Despite that all virus variants were able to grow in mammalian cell lines, they were unable to spread efficiently in cells of mosquito origin. Moreover, in vivo studies demonstrated that RVFV-4s is unable to cause disseminated infection and disease in mice, even in the presence of the main virulence factor NSs, but induced a protective immune response against a lethal challenge with wild-type virus. In summary, splitting bunyavirus glycoprotein precursor genes provides new opportunities to study bunyavirus genome packaging and offers new methods to develop next-generation live-attenuated bunyavirus vaccines. Rift Valley fever virus (RVFV) causes devastating disease in ruminants and occasionally humans. Virions capable of productive infection comprise at least one copy of the small (S), medium (M), and large (L) RNA genome segments. The M segment encodes a glycoprotein precursor (GPC) protein that is cotranslationally cleaved into Gn and Gc, which are required for virus entry and fusion. We studied the flexibility of RVFV genome packaging and developed experimental live-attenuated vaccines by applying a unique strategy based on the splitting of the GnGc open reading frame. Several RVFV variants, varying from viruses comprising two S-type segments to viruses consisting of four segments (RVFV-4s), of which three are M-type, could be rescued and were shown to induce a rapid protective immune response. Altogether, the segmentation of bunyavirus GPCs provides a new method for studying bunyavirus genome packaging and facilitates the development of novel live-attenuated bunyavirus vaccines. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

ZIP4 silencing improves bone loss in pancreatic cancer

PubMed Central

Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

2015-01-01

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

The unmet need for philanthropic funding of early career cardiovascular investigators.

PubMed

Ahmad, Tariq; Becker, Richard C

2014-05-01

Philanthropic donations have funded scientific investigations of cardiovascular disease for much of human history, and the patrons who enabled them are indirectly responsible for major breakthroughs in the field. Today, however, the lion's share of funding for cardiovascular research in Western countries comes from the government, professional agencies, and industry. Rapid budget cuts at these traditional sources of financial support are having a devastating impact on the cardiovascular research infrastructure by slashing funding for investigators. A particularly unfortunate consequence is the discouraging effect this is having on early career investigators, who are the life-blood of future breakthroughs in the field, leading to the potential loss of an entire generation of researchers. Here, we summarize the challenges faced by emerging cardiovascular investigators, make a case for the unmet need for appropriately targeted philanthropic support for cardiovascular research, and provide a roadmap for solving the funding shortfall for these investigators.

Genetic and biochemical analysis of protozoal polyamine transporters.

PubMed

Hasne, Marie-Pierre; Ullman, Buddy

2011-01-01

Polyamines are aliphatic polycations that function in key cellular processes such as growth, differentiation, and macromolecular biosynthesis. Intracellular polyamines pools are maintained from de novo synthesis and from transport of polyamines from the extracellular milieu. This acquisition of exogenous polyamines is mediated by cell surface transporter proteins. Protozoan parasites are the etiologic agents of a plethora of devastating and often fatal diseases in humans and their domestic animals. These pathogens accommodate de novo and/or salvage mechanisms for polyamine acquisition. Because of its therapeutic relevance, the polyamine biosynthetic pathway has been thoroughly investigated in many genera of protozoan parasites, but the polyamine permeation pathways have generally been ignored. Our group has now identified at the molecular level polyamine transporters from two species of protozoan parasites, Leishmania major and Trypanosoma cruzi, characterized these polytopic proteins with respect to ligand specificities and affinities, and determined the subcellular environments in which these transporters reside.

Mycobacterial glycolipids di-O-acylated trehalose and tri-O-acylated trehalose downregulate inducible nitric oxide synthase and nitric oxide production in macrophages.

PubMed

Espinosa-Cueto, Patricia; Escalera-Zamudio, Marina; Magallanes-Puebla, Alejandro; López-Marín, Luz María; Segura-Salinas, Erika; Mancilla, Raúl

2015-06-23

Tuberculosis (TB) remains a serious human health problem that affects millions of people in the world. Understanding the biology of Mycobacterium tuberculosis (Mtb) is essential for tackling this devastating disease. Mtb possesses a very complex cell envelope containing a variety of lipid components that participate in the establishment of the infection. We have previously demonstrated that di-O-acylated trehalose (DAT), a non-covalently linked cell wall glycolipid, inhibits the proliferation of T lymphocytes and the production of cytokines. In this work we show that DAT and the closely related tri-O-acylated trehalose (TAT) inhibits nitric oxide (NO) production and the inducible nitric oxide synthase (iNOS) expression in macrophages (MØ). These findings show that DAT and TAT are cell-wall located virulence factors that downregulate an important effector of the immune response against mycobacteria.

Invasion genetics of emerald ash borer (Agrilus planipennis Fairmaire)

Treesearch

Alicia M. Bray; Leah S. Bauer; Therese M. Poland; Bob A. Haack; James J. Smith

2011-01-01

Emerald ash borer (EAB), Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), is a devastating invasive pest of North American ash trees (Fraxinus spp.) that was first discovered outside of its native range of northeastern Asia in 2002 (Haack et al. 2002). With unintended assistance from human movement of infested ash material...

Three Campus Crises: Lessons for Administrators.

ERIC Educational Resources Information Center

Rothman, Michael

1992-01-01

In October 1989-October 1991, Mills College (California) faced three crises: an earthquake; a strike over plans to convert to a coeducational institution; and a devastating fire in the area. The college has learned to focus its structural, human, political, and symbolic frames of reference; communicate; plan; consider the public; and develop…

454 pyrosequencing project on expressed genes from the New World Screwworm, Cochliomyia hominivorax

USDA-ARS?s Scientific Manuscript database

The New World screwworm, Cochliomyia hominivorax, was a devastating pest of livestock and other animals, including humans, throughout the US, Mexico and Central America. Although eradicated from North America, the screwworm still is a pest in South America and the Caribbean. Reinfestation of North A...

Bigger than a Breadbox; Lighter than a Heavy Heart

ERIC Educational Resources Information Center

Hill, Robert V.

2009-01-01

Inexact measurements can have devastating effects in sciences where precision is of paramount importance. In contrast, morphological sciences rely heavily on description, comparison, and estimation to make meaningful inferences about the structure of humans and other animals. A review of the 1918 edition of "Gray's Anatomy" shows that the tendency…

Technological Lessons from the Fukushima Dai-Ichi Accident

DTIC Science & Technology

2016-06-01

for human consumption . Fish from the area are now being assessed using a non-destructive testing regimen developed by Tohoku University. Monitoring...radioactivity limits for human consumption , even though much of the rice was grown in con- taminated soil. Fish were contaminated both by the initial event...a devastating earth- quake and tsunami. One of the many secondary effects of these disas- ters was a loss of control of the Fukushima Dai-Ichi nuclear

Characterization of stem rust resistance in wheat cultivar 'Gage'

USDA-ARS?s Scientific Manuscript database

Wheat (Triticum spp.) stem rust, caused by Puccinia graminis f. sp. tritici Eriks. & E. Henn. (Pgt), re-emerged as a devastating disease of wheat because of virulent race Ug99 (TTKSK). Many bread wheat (T. aestivum L.) cultivars grown in North America are susceptible to Ug99 or its derivative races ...

Elevated [CO2] compromises both Type I and Type II wheat resistance to Fusarium head blight

USDA-ARS?s Scientific Manuscript database

Fusarium head blight (FHB) is one of the world’s most devastating wheat diseases, and results in significant yield loss and contamination of grain with harmful mycotoxins called trichothecenes. Despite emerging risks of increased mycotoxin contamination in food and feed associated with climate chang...

Effects of interferon-alpha on the immune response to porcine reproductive and respiratory syndrome virus

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry world-wide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak and results in delayed elimination of virus from the host and inferior vaccine protection. PR...

Genome Sequences of 19 Novel Erwinia amylovora Bacteriophages

PubMed Central

Esplin, Ian N. D.; Berg, Jordan A.; Sharma, Ruchira; Allen, Robert C.; Arens, Daniel K.; Ashcroft, Cody R.; Bairett, Shannon R.; Beatty, Nolan J.; Bickmore, Madeline; Bloomfield, Travis J.; Brady, T. Scott; Bybee, Rachel N.; Carter, John L.; Choi, Minsey C.; Duncan, Steven; Fajardo, Christopher P.; Foy, Brayden B.; Fuhriman, David A.; Gibby, Paul D.; Grossarth, Savannah E.; Harbaugh, Kala; Harris, Natalie; Hilton, Jared A.; Hurst, Emily; Hyde, Jonathan R.; Ingersoll, Kayleigh; Jacobson, Caitlin M.; James, Brady D.; Jarvis, Todd M.; Jaen-Anieves, Daniella; Jensen, Garrett L.; Knabe, Bradley K.; Kruger, Jared L.; Merrill, Bryan D.; Pape, Jenny A.; Payne Anderson, Ashley M.; Payne, David E.; Peck, Malia D.; Pollock, Samuel V.; Putnam, Micah J.; Ransom, Ethan K.; Ririe, Devin B.; Robinson, David M.; Rogers, Spencer L.; Russell, Kerri A.; Schoenhals, Jonathan E.; Shurtleff, Christopher A.; Simister, Austin R.; Smith, Hunter G.; Stephenson, Michael B.; Staley, Lyndsay A.; Stettler, Jason M.; Stratton, Mallorie L.; Tateoka, Olivia B.; Tatlow, P. J.; Taylor, Alexander S.; Thompson, Suzanne E.; Townsend, Michelle H.; Thurgood, Trever L.; Usher, Brittian K.; Whitley, Kiara V.; Ward, Andrew T.; Ward, Megan E. H.; Webb, Charles J.; Wienclaw, Trevor M.; Williamson, Taryn L.; Wells, Michael J.; Wright, Cole K.; Breakwell, Donald P.; Hope, Sandra

2017-01-01

ABSTRACT Erwinia amylovora is the causal agent of fire blight, a devastating disease affecting some plants of the Rosaceae family. We isolated bacteriophages from samples collected from infected apple and pear trees along the Wasatch Front in Utah. We announce 19 high-quality complete genome sequences of E. amylovora bacteriophages. PMID:29146842

Development of a duplex ddPCR assay for detection of “Candidatus Liberibacter asiaticus”

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) (aka citrus greening) is a devastating citrus disease associated with “Candidatus Liberibacter asiaticus” (CLas). Currently, diagnosis of CLas in regulatory samples is based on a real-time quantitative polymerase chain reaction (qPCR) assay using 16S rRNA gene specific primers/pr...

QTL mapping of downy mildew resistance in PI 197088 and PI 330628 cucumbers

USDA-ARS?s Scientific Manuscript database

Downy mildew (DM, Pseudoperonospora cubensis) is a devastating fungal disease of cucumber worldwide. Several plant introduction lines have been identified with high resistance to the post-2004 new DM strain found in the U.S. However, the inheritance of DM resistance is still not well defined. Molecu...

Vaccination with Eimeria tenella Elongation Factor-1alpha Recombinant Protein Induces protective Immunity against E. tenella and E. maxima infections

USDA-ARS?s Scientific Manuscript database

Avian coccidiosis is caused by multiple species of the apicomplexan protozoan, Eimeria, and is one of the most economically devastating enteric diseases for the poultry industry worldwide. Host immunity to Eimeria infection, however, is relatively species-specific. The ability to immunize chickens a...

Deciphering the bacterial microbiome of citrus plants in response to ‘Candidatus Liberibacter asiaticus’-infection and antibiotic treatment

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB), the most devastating citrus disease worldwide, is vectored by phloem-feeding insects, and the pathogen in the USA is Candidatus Liberibacter asiaticus (Las). The bacterial microbiome of citrus after Las-infection and treatments with ampicillin (Amp) and gentamicin (Gm) was chara...

Analysis of apple (Malus) responses to bacterial pathogens using an oligo microarray

USDA-ARS?s Scientific Manuscript database

Fire blight is a devastating disease of apple (Malus x domestica) caused by the bacterial pathogen Erwinia amylovora (Ea). When infiltrated into host leaves, Ea induces reactions similar to a hypersensitive response (HR). Type III (T3SS) associated effectors, especially DspA/E, are suspected to ha...

Registration of an oilseed sunflower germplasm line HA-BSR1 highly tolerant to Sclerotinia basal stalk rot

USDA-ARS?s Scientific Manuscript database

Basal stalk rot (BSR) caused by Sclerotinia sclerotiorum (Lib.) de Bary is a devastating disease that causes a significant damage to worldwide sunflower (Helianthus annuus L.) production by reducing seed yield and quality. The objective of this research was to develop highly BSR tolerant sunflower g...

Influence of Varroa mite (Varroa destructor) infestation levels and management practices on insecticide sensitivity in the honey bee (Apis mellifera)

USDA-ARS?s Scientific Manuscript database

Because Varroa mites may cause devastating losses of honey bees through direct feeding, transmitting diseases, and increasing pathogen susceptibility, chemical and mechanical practices commonly are used to reduce mite infestation. While miticide applications are typically the most consistent and eff...

A real-time PCR assay for early detection of eastern filbert blight

USDA-ARS?s Scientific Manuscript database

Eastern filbert blight (EFB) is a devastating disease of European hazelnut, Corylus avellana, which causes economic losses in Oregon where 99% of the U.S. crop is produced. The causal fungus, Anisogramma anomala, is native to eastern North America, where it is found associated with the American haz...

A simple culture method inducing sexual reproduction by Fusarium graminearum, the primary causal agent of Fusarium head blight

USDA-ARS?s Scientific Manuscript database

The homothallic ascomycete fungus Fusarium graminearum is the primary causal agent of Fusarium head blight (FHB), a devastating disease of wheat and barley worldwide. The fungus undergoes both asexual and sexual stages in its life cycle. The asexual stage produces conidiospores, whereas the sexual s...

Diaphorina citri (Hemiptera: Liviidae) responses to microcontroller-buzzer communication signals of potential use in vibration traps

USDA-ARS?s Scientific Manuscript database

Monitoring of Diaphorina citri Kuwayama populations is an important component of efforts to reduce damage caused by huanglongbing, a devastating disease it vectors in citrus groves. Currently, D. citri is monitored primarily by unbaited sticky traps or visual inspection of trees. A potentially more ...

Protection and coexistence of conventional papaya productions with PRSV resistant transgenic papaya

USDA-ARS?s Scientific Manuscript database

Papaya ringspot virus (PRSV) is a devastating disease that has a detrimental impact on both commercial papaya production and Caricaceae germplasm conservation. Transgenic line 55-1 and derived progeny ‘SunUp’ and ‘Rainbow’ are resistant to PRSV and have saved the papaya industry in Hawaii. In small...

Pre- and post-harvest development of Phytophthora fruit rot on watermelons treated with fungicides in the field

USDA-ARS?s Scientific Manuscript database

Fruit rot, caused by Phytophthora capsici, is a serious disease in most watermelon producing regions in southeastern U.S., and has caused devastating loss over the past few years. In many instances, severe losses occurred after harvest during transportation. Experiments were conducted in 2010, 201...

Dothistroma Needle Blight of Pines

Treesearch

Glenn W. Peterson

1982-01-01

Dothistroma blight is a devastating foliar disease of a wide range of pine species. The causal fungus, Dothistroma pini Hulbary, infects and kills needles. Premature defoliation caused by this fungus has resulted in complete failure of most ponderosa pine plantings in States east of the Great Plains. In the central and southern Great Plains, D. pini damages Austrian...

Toward The Identification Of Candidate Genes Involved In Black Pod Disease Resistance In Theobroma cacao L.

USDA-ARS?s Scientific Manuscript database

Black Pod (Phytophthora sp.) has a devastating effect on the worldwide cacao (Theobroma cacao) yield and incorporating resistance into production fields has been an ongoing effort of breeding programs. Previous meta-QTL analysis of genetic maps created with a variety of molecular markers identified...

Toward the identification of candidate genes involved In black pod disease resistance in Theobroma cacao L.

USDA-ARS?s Scientific Manuscript database

Black Pod (Phytophthora sp.) has a devastating effect on the worldwide cacao (Theobroma cacao) yield and incorporating resistance into production fields has been an ongoing effort of breeding programs. Previous meta-QTL analysis of genetic maps created with a variety of molecular markers identified...

Behavioral responses of male Diaphorina citri (Hemiptera: Liviidae) to mating communication signals from vibration traps in citrus (Sapindales: Rutaceae) trees

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid, Diaphorina citri Kuwayama, vectors the bacterium causing citrus greening disease, which has devastated citrus production worldwide wherever it has been introduced. To help monitor and target D citri populations in commercial groves, thereby facilitating more effective manag...

Powder Keg on the Upper Missouri: Sources of Blackfeet Hostility, 1730-1810.

ERIC Educational Resources Information Center

Judy, Mark A.

1987-01-01

Evaluates reasons why Blackfeet Indians were bitterly hostile toward white fur traders in the upper Missouri River basin during the early 1800s. Explains causes of internal tribal turmoil including rapid adaptation of horses to tribal culture, devastating effects of disease, and guns disrupting the balance of power among tribes. (JHZ)

Comparative “omics” of the Fusarium fujikuroi species complex highlights differences in genetic potential and metabolite synthesis

USDA-ARS?s Scientific Manuscript database

Species of the Fusarium fujikuroi species complex (FFC) cause a wide spectrum of often devastating diseases on diverse agricultural crops, including coffee, fig, mango, maize, rice, and sugarcane. Although species within the FFC are difficult to distinguish by morphology, and their genes often share...

The destructive citrus pathogen, ‘Candidatus Liberibacter asiaticus’ encodes a functional flagellin characteristic of a pathogen-associated molecular pattern

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB) is presently the most devastating citrus disease worldwide. As an intracellular plant pathogen and insect symbiont, the HLB bacterium, ‘Candidatus Liberibacter asiaticus’ (Las) retains the entire flagellum-encoding gene cluster in its significantly reduced genome. Las encodes a...

Plum orchards can remain Plum pox virus free for the life of the orchard

USDA-ARS?s Scientific Manuscript database

Plum pox virus (PPV), the cause of sharka disease, is a quarantine virus pathogen that can cause devastating losses mainly to plum. Estimated costs associated with sharka management worldwide in the last 30 years exceeded 10 billion Euros. To prevent the spread of PPV, we suggest three requirement...

Conservation of genetic diversity in slippery elm (Ulmus rubra) in Wisconsin despite the devastating impact of Dutch elm disease

USDA-ARS?s Scientific Manuscript database

Forest trees tend to be genetically diverse, a condition related to their longevity, outcrossing mating system and extensive gene flow that maintains high levels of genetic diversity within populations. Forest pest epidemics are responsible for many historic and contemporary population declines repo...

Bioassay conditions for infection of Pinus radiata seedlings with Phytophthora pinifolia zoospores

USDA-ARS?s Scientific Manuscript database

Phytophthora pinifolia is known to cause a devastating disease on Monterey pines in Chile. Although this pathogen is not yet present in the U.S., there is reason for concern. The main source of Monterey pine genetic material is found in California and there is potential for other important tree sp...

AIDS Researcher Gives Retrospective

ERIC Educational Resources Information Center

Hawkins, B. Denise

2011-01-01

Nearly 30 years ago, renowned immunologist James E.K. Hildreth, M.D., Ph.D., was compelled to start researching the virus that causes AIDS. He marveled at its enigma and was pressed into action by its ability to cut lives short and devastate communities. The disease set him on a course of medical inquiry that has included biomedical breakthroughs…

Sources of stem rust resistance in wheat-alien introgression lines

USDA-ARS?s Scientific Manuscript database

Stem rust, caused by Puccinia graminis f. sp. tritici, is one of the most devastating diseases of wheat and the novel highly virulent race of TTKSK and its lineage are threatening wheat production worldwide. The objective of the study was to identify new sources of resistance in wheat-alien introgre...

Detection of wheat stem rust race RRTTF in Ecuador in 2016

USDA-ARS?s Scientific Manuscript database

Wheat stem rust is a devastating disease that has incited numerous severe epidemics resulting in extreme yield losses over the past century. Stem rust infection in plots of wheat line UC11075, known to carry the Sr38 resistance gene, was severe in February 2016 in a nursery at the Instituto Nacional...

Genomic dissection of nonhost resistance to wheat stem rust in Brachypodium distachyon

USDA-ARS?s Scientific Manuscript database

Wheat stem rust caused by the fungus Puccinia graminis f.sp. tritici (Pgt) is a devastating disease that has largely been controlled for decades by the deployment of resistance genes. However, new races of this pathogen have emerged that overcome many important wheat stem rust resistance genes used ...

Lived Experience of Women Suffering from Vitiligo: A Phenomenological Study

ERIC Educational Resources Information Center

Borimnejad, Leili; Yekta, Zohreh Parsa; Nasrabadi, Alireza Nikbakht

2006-01-01

Vitiligo is a chronic skin disease, which through change of appearance and body image, exerts a devastating effect on people, especially women. The objective of this study is to explore lived experience of women with Vitiligo by the hermeneutic phenomenology method. The purposive sample consisted of 16 Iranian women. Data analysis followed…

A SNP mutation affects rhizomania-virus content of sugar beets grown on resistance-breaking soi

USDA-ARS?s Scientific Manuscript database

Rhizomania is one of the most devastating biotic stresses affecting sugar beet (Beta vulgaris L.). It is caused by Beet necrotic yellow vein virus (BNYVV) vectored by the plasmodiophorid Polymyxa betae K. The only means available to control the disease is the use of genetically resistant varieties. ...

Cassava brown streak virus has a rapidly evolving genome: implications for virus speciation, variability, diagnosis and host resistance

PubMed Central

Alicai, Titus; Ndunguru, Joseph; Sseruwagi, Peter; Tairo, Fred; Okao-Okuja, Geoffrey; Nanvubya, Resty; Kiiza, Lilliane; Kubatko, Laura; Kehoe, Monica A.; Boykin, Laura M.

2016-01-01

Cassava is a major staple food for about 800 million people in the tropics and sub-tropical regions of the world. Production of cassava is significantly hampered by cassava brown streak disease (CBSD), caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). The disease is suppressing cassava yields in eastern Africa at an alarming rate. Previous studies have documented that CBSV is more devastating than UCBSV because it more readily infects both susceptible and tolerant cassava cultivars, resulting in greater yield losses. Using whole genome sequences from NGS data, we produced the first coalescent-based species tree estimate for CBSV and UCBSV. This species framework led to the finding that CBSV has a faster rate of evolution when compared with UCBSV. Furthermore, we have discovered that in CBSV, nonsynonymous substitutions are more predominant than synonymous substitution and occur across the entire genome. All comparative analyses between CBSV and UCBSV presented here suggest that CBSV may be outsmarting the cassava immune system, thus making it more devastating and harder to control. PMID:27808114

Calciphylaxis: a devastating complication of derangements of calcium-phosphorus metabolism--a case report and review of the literature.

PubMed

Carter, Trish; Ratnam, Shobha

2013-01-01

Calciphylaxis is a rare and potentially devastating condition also referred to as uremic gangrene syndrome, calcific uremic arteriolopathy, metastatic calcification, and uremic small-vessel disease that can present in patients with end stage renal disease. This article reports a case of a 38-year-old African-American female on peritoneal dialysis for six years with a known history of non-adherence with diet, medications, and prescribed peritoneal dialysis treatment regimen. At her monthly clinic visit, the patient complained of burning sensation in the fingers of both hands with limited fine motor movement due to edema and severe pain. A presumptive diagnosis of calciphylaxis led to hospital admission with confirmation by X-ray of her hands. The patient was switched to hemodialysis with low calcium dialysate, aggressive reduction in phosphorus, diet counseling, use of cinacalcet, and six weeks of intravenous sodium thiosulfate infusion with hemodialysis treatments. The patient's condition improved with resolution of symptoms. This case was chosen based on the rarity of a calciphylaxis presentation and paucity of knowledge regarding diagnosis and treatment.

Production and characterization of murine models of classic and intermediate maple syrup urine disease

PubMed Central

Homanics, Gregg E; Skvorak, Kristen; Ferguson, Carolyn; Watkins, Simon; Paul, Harbhajan S

2006-01-01

Background Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has several clinical phenotypes depending on the degree of enzyme deficiency. Current treatments are not satisfactory and require new approaches to combat this disease. A major hurdle in developing new treatments has been the lack of a suitable animal model. Methods To create a murine model of classic MSUD, we used gene targeting and embryonic stem cell technologies to create a mouse line that lacked a functional E2 subunit gene of branched-chain keto acid dehydrogenase. To create a murine model of intermediate MSUD, we used transgenic technology to express a human E2 cDNA on the knockout background. Mice of both models were characterized at the molecular, biochemical, and whole animal levels. Results By disrupting the E2 subunit gene of branched-chain keto acid dehydrogenase, we created a gene knockout mouse model of classic MSUD. The homozygous knockout mice lacked branched-chain keto acid dehydrogenase activity, E2 immunoreactivity, and had a 3-fold increase in circulating branched-chain amino acids. These metabolic derangements resulted in neonatal lethality. Transgenic expression of a human E2 cDNA in the liver of the E2 knockout animals produced a model of intermediate MSUD. Branched-chain keto acid dehydrogenase activity was 5–6% of normal and was sufficient to allow survival, but was insufficient to normalize circulating branched-chain amino acids levels, which were intermediate between wildtype and the classic MSUD mouse model. Conclusion These mice represent important animal models that closely approximate the phenotype of humans with the classic and intermediate forms of MSUD. These animals provide useful models to further characterize the pathogenesis of MSUD, as well as models to test novel therapeutic strategies, such as gene and cellular therapies, to treat this devastating metabolic disease. PMID:16579849

Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells.

PubMed

Molina-Molina, M; Machahua-Huamani, C; Vicens-Zygmunt, V; Llatjós, R; Escobar, I; Sala-Llinas, E; Luburich-Hernaiz, P; Dorca, J; Montes-Worboys, A

2018-04-27

Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor β1 (TGF-β). Extracellular matrix protein and gene expression of markers involved in lung fibrosis (tenascin-c, fibronectin, collagen I [COL1A1], collagen III [COL3A1] and α-smooth muscle actin [α-SMA]) were analyzed. A cell migration assay in pirfenidone, rapamycin and TGF-β-containing media was performed. Gene and protein expression of tenascin-c and fibronectin of fibrotic fibroblasts were reduced by pirfenidone or rapamycin treatment. Pirfenidone-rapamycin treatment did not revert the epithelial to mesenchymal transition pathway activated by TGF-β. However, the drug combination significantly abrogated fibroblast to myofibroblast transition. The inhibitory effect of pirfenidone on fibroblast migration in the scratch-wound assay was potentiated by rapamycin combination. These findings indicate that the combination of pirfenidone and rapamycin widen the inhibition range of fibrogenic markers and prevents fibroblast migration. These results would open a new line of research for an anti-fibrotic combination therapeutic approach.

Patient perspectives on quality of life after penile cancer.

PubMed

Mortensen, Gitte Lee; Jakobsen, Jakob Kristian

2013-07-01

Penile cancer (PC) is a rare, but ominous disease. In 50-60% of squamous cell carcinomas of the penis, human papilloma virus infection, particularly with types 16 and 18, is part of the pathogenesis. Depending on cancer invasiveness, PC is treated with local resection of the glans and partial or total penectomy. This quality of life (QoL) study aimed at obtaining in-depth knowledge about patients' experiences with PC. A literature study was carried out to identify relevant topics for a semi-structured interview. Qualitative interviews with four former PC patients were transcribed verbatim and analysed using a medical anthropological approach. The analysis focused on the ways patients frame their disease experiences and relate the physical, sexual and emotional disease impact. Varying degrees of amputation affected the participants' sexual capabilities. Still, three participants (aged 66-72 years) said that their partner relationships were not negatively affected by the disease. In contrast, the impact on sexual function and self-esteem had been devastating to the fourth participant (aged 44 years) who was single and worried about the disease impeding his chance of finding love in life. For all participants, having had a potentially fatal disease put the physical disease impact into perspective. PC may greatly impact the psycho-sexual QoL of PC patients, particularly at a younger age and depending on their partnership status. Disease impact appears to be related to age, overall life situation and the cancer experience. The study was funded by an unrestricted research grant from Sanofi Pasteur MSD. not relevant.

A Participatory System for Preventing Pandemics of Animal Origins: Pilot Study of the Participatory One Health Disease Detection (PODD) System.

PubMed

Yano, Terdsak; Phornwisetsirikun, Somphorn; Susumpow, Patipat; Visrutaratna, Surasing; Chanachai, Karoon; Phetra, Polawat; Chaisowwong, Warangkhana; Trakarnsirinont, Pairat; Hemwan, Phonpat; Kaewpinta, Boontuan; Singhapreecha, Charuk; Kreausukon, Khwanchai; Charoenpanyanet, Arisara; Robert, Chongchit Sripun; Robert, Lamar; Rodtian, Pranee; Mahasing, Suteerat; Laiya, Ekkachai; Pattamakaew, Sakulrat; Tankitiyanon, Taweesart; Sansamur, Chalutwan; Srikitjakarn, Lertrak

2018-03-21

Aiming for early disease detection and prompt outbreak control, digital technology with a participatory One Health approach was used to create a novel disease surveillance system called Participatory One Health Disease Detection (PODD). PODD is a community-owned surveillance system that collects data from volunteer reporters; identifies disease outbreak automatically; and notifies the local governments (LGs), surrounding villages, and relevant authorities. This system provides a direct and immediate benefit to the communities by empowering them to protect themselves. The objective of this study was to determine the effectiveness of the PODD system for the rapid detection and control of disease outbreaks. The system was piloted in 74 LGs in Chiang Mai, Thailand, with the participation of 296 volunteer reporters. The volunteers and LGs were key participants in the piloting of the PODD system. Volunteers monitored animal and human diseases, as well as environmental problems, in their communities and reported these events via the PODD mobile phone app. LGs were responsible for outbreak control and provided support to the volunteers. Outcome mapping was used to evaluate the performance of the LGs and volunteers. LGs were categorized into one of the 3 groups based on performance: A (good), B (fair), and C (poor), with the majority (46%,34/74) categorized into group B. Volunteers were similarly categorized into 4 performance groups (A-D), again with group A showing the best performance, with the majority categorized into groups B and C. After 16 months of implementation, 1029 abnormal events had been reported and confirmed to be true reports. The majority of abnormal reports were sick or dead animals (404/1029, 39.26%), followed by zoonoses and other human diseases (129/1029, 12.54%). Many potentially devastating animal disease outbreaks were detected and successfully controlled, including 26 chicken high mortality outbreaks, 4 cattle disease outbreaks, 3 pig disease outbreaks, and 3 fish disease outbreaks. In all cases, the communities and animal authorities cooperated to apply community contingency plans to control these outbreaks, and community volunteers continued to monitor the abnormal events for 3 weeks after each outbreak was controlled. By design, PODD initially targeted only animal diseases that potentially could emerge into human pandemics (eg, avian influenza) and then, in response to community needs, expanded to cover human health and environmental health issues. ©Terdsak Yano, Somphorn Phornwisetsirikun, Patipat Susumpow, Surasing Visrutaratna, Karoon Chanachai, Polawat Phetra, Warangkhana Chaisowwong, Pairat Trakarnsirinont, Phonpat Hemwan, Boontuan Kaewpinta, Charuk Singhapreecha, Khwanchai Kreausukon, Arisara  Charoenpanyanet, Chongchit Sripun Robert, Lamar Robert, Pranee Rodtian, Suteerat Mahasing, Ekkachai Laiya, Sakulrat Pattamakaew, Taweesart Tankitiyanon, Chalutwan Sansamur, Lertrak Srikitjakarn. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 21.03.2018.

Development of vaccines against Crimean-Congo haemorrhagic fever virus.

PubMed

Dowall, Stuart D; Carroll, Miles W; Hewson, Roger

2017-10-20

Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the utmost seriousness being highly lethal causing devastating disease symptoms that result in intense and prolonged suffering to those infected. During the past 40years, this virus has repeatedly caused sporadic outbreaks responsible for relatively low numbers of human casualties, but with an alarming fatality rate of up to 80% in clinically infected patients. CCHFV is transmitted to humans by Hyalomma ticks and contact with the blood of viremic livestock, additionally cases of human-to-human transmission are not uncommon in nosocomial settings. The incidence of CCHF closely matches the geographical range of permissive ticks, which are widespread throughout Africa, Asia, the Middle East and Europe. As such, CCHFV is the most widespread tick-borne virus on earth. It is a concern that recent data shows the geographic distribution of Hyalomma ticks is expanding. Migratory birds are also disseminating Hyalomma ticks into more northerly parts of Europe thus potentially exposing naïve human populations to CCHFV. The virus has been imported into the UK on two occasions in the last five years with the first fatal case being confirmed in 2012. A licensed vaccine to CCHF is not available. In this review, we discuss the background and complications surrounding this limitation and examine the current status and recent advances in the development of vaccines against CCHFV. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Establishing the UK DNA Bank for motor neuron disease (MND).

PubMed

Smith, Lucy; Cupid, B C; Dickie, B G M; Al-Chalabi, A; Morrison, K E; Shaw, C E; Shaw, P J

2015-07-14

In 2003 the Motor Neurone Disease (MND) Association, together with The Wellcome Trust, funded the creation of a national DNA Bank specific for MND. It was anticipated that the DNA Bank would constitute an important resource to researchers worldwide and significantly increase activity in MND genetic research. The DNA Bank houses over 3000 high quality DNA samples, all of which were donated by people living with MND, family members and non-related controls, accompanied by clinical phenotype data about the patients. Today the primary focus of the UK MND DNA Bank still remains to identify causative and disease modifying factors for this devastating disease.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Susheela, A.K.

Fluorosis, a crippling disease caused by ingesting excess fluoride in drinking water, is a public health problem, affecting people in 20 nations in the world. One of the worst public health problems in the history of mankind known to have occurred and reported about 6 decades ago strangely enough the disease continue to be afflicting millions of people in India, Africa and China with all its severity even during the turn of the century. The present report describes the disease characteristics and the devastating manner in which the disease affects children and adults. The need to bring this to themore » attention of policy, makers, has been attempted.« less

Cognitive impairment and pragmatics.

PubMed

Gutiérrez-Rexach, Javier; Schatz, Sara

2016-01-01

One of the most important ingredients of felicitous conversation exchanges is the adequate expression of illocutionary force and the achievement of perlocutionary effects, which can be considered essential to the functioning of pragmatic competence. The breakdown of illocutionary and perlocutionary functions is one of the most prominent external features of cognitive impairment in Alzheimer's Disease, with devastating psychological and social consequences for patients, their family and caregivers. The study of pragmatic functions is essential for a proper understanding of the linguistic and communicative aspects of Alzheimer's disease.

Recognition and treatment of neuropsychiatric disturbances in Parkinson's disease.

PubMed

Akbar, Umer; Friedman, Joseph H

2015-01-01

The non-motor symptoms of Parkinson's disease (PD) have been attracting increasing attention due to their ubiquitous nature and their often devastating effects on the quality of life. Behavioral problems in PD include dementia, depression, apathy, fatigue, anxiety, psychosis, akathisia, personality change, sleep disorders and impulse control disorders. Some of these are intrinsic to the neuropathology while others occur as an interplay between pathology, psychology and pharmacology. While few data exist for guiding therapy, enough is known to guide therapy in a rational manner.

A case of Apophysomyces trapeziformis necrotizing soft tissue infection.

PubMed

Echaiz, Jose F; Burnham, Carey-Ann D; Bailey, Thomas C

2013-12-01

Mucormycosis is a rare and devastating disease. Apophysomyces trapeziformis is an environmental mold that was recently implicated in several cases of cutaneous and soft tissue mucormycosis in victims of a tornado in Joplin, Missouri. Here, we report a case of Apophysomyces trapeziformis necrotizing soft tissue infection in a resident of Joplin 10 months after the disaster and without preceding trauma. Aspects of histological and microbiological diagnosis are also reviewed. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Empowering Local Organizations and Decision-makers in a Changing Climate: EO-guided Environmental Surveillance of Cholera and Rotavirus for South Asia

NASA Astrophysics Data System (ADS)

Akanda, A. S.; Hasan, M. A.; Jutla, A.; Aziz, S.; Alam, M.; Ahsan, G. U.; Huq, A.; Colwell, R. R.

2017-12-01

Despite significant advancements in scientific research, diarrheal diseases remain a leading cause of mortality and morbidity in the developing world. Although under-5 child mortality due to such diseases is dropping, prevalence of most diarrheal diseases has increased over past decades, exerting a terrible toll on global public health. Providing safe water and sanitation access, and a safe and clean environment in a sustainable manner remains a critical challenge in the face of rapid population growth, urbanization and increasing threats of natural hazards in a changing climate. We focus on the Bengal Delta region of South Asia, where Cholera and Rotavirus diarrhea continue to have a devastating impact on the public health burden. Climatic change and anthropogenic forcings have greatly affected available water quantity and quality, while the lack of effective institutions and capacity have greatly affected the water-sanitation and public health sectors. The region suffers from recurring dry season freshwater scarcity and temperature extremes, salinity intrusion in coastal areas, inland flooding during monsoons, and resulting water contamination across the delta region. We use earth observation (EO) datasets and techniques to develop a series of tools for surveillance, analysis and decision support to empower government, academic, and non-government stakeholder organizations in South Asia to monitor changes in environmental conditions related to the two most devastating diarrheal diseases, cholera and rotavirus. The developed tools will enable decision makers and stakeholders to significantly increase their understanding of the threats to public health and environmental and climatic conditions related to these diseases, ways to monitor future projections of disease risk, and help identify required policy interventions and strategies to strengthen prevention efforts and limit disease burden in near- (tactical) and long- (strategic) terms.

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

PubMed Central

Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

2015-01-01

Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

Hypothalamic Mechanisms in Cachexia

PubMed Central

Grossberg, Aaron J.; Scarlett, Jarrad M.; Marks, Daniel L.

2010-01-01

The role of nutrition and balanced metabolism in normal growth, development, and health maintenance is well known. Patients affected with either acute or chronic diseases often show disorders of nutrient balance. In some cases, a devastating state of malnutrition known as cachexia arises, brought about by a synergistic combination of a dramatic decrease in appetite and an increase in metabolism of fat and lean body mass. Other common features that are not required for the diagnosis include decreases in voluntary movement, insulin resistance, and anhedonia. This combination is found in a number of disorders including cancer, cystic fibrosis, AIDS, rheumatoid arthritis, renal failure, and Alzheimer's disease. The severity of cachexia in these illnesses is often the primary determining factor in both quality of life, and in eventual mortality. Indeed, body mass retention in AIDS patients has a stronger association with survival than any other current measure of the disease. This has led to intense investigation of cachexia and the proposal of numerous hypotheses regarding its etiology. Most authors suggest that cytokines released during inflammation and malignancy act on the central nervous system to alter the release and function of a number of neurotransmitters, thereby altering both appetite and metabolic rate. This review will discuss the salient features of cachexia in human diseases, and review the mechanisms whereby inflammation alters the function of key brain regions to produce stereotypical illness behavior. PMID:20346963

A yeast functional screen predicts new candidate ALS disease genes

PubMed Central

Couthouis, Julien; Hart, Michael P.; Shorter, James; DeJesus-Hernandez, Mariely; Erion, Renske; Oristano, Rachel; Liu, Annie X.; Ramos, Daniel; Jethava, Niti; Hosangadi, Divya; Epstein, James; Chiang, Ashley; Diaz, Zamia; Nakaya, Tadashi; Ibrahim, Fadia; Kim, Hyung-Jun; Solski, Jennifer A.; Williams, Kelly L.; Mojsilovic-Petrovic, Jelena; Ingre, Caroline; Boylan, Kevin; Graff-Radford, Neill R.; Dickson, Dennis W.; Clay-Falcone, Dana; Elman, Lauren; McCluskey, Leo; Greene, Robert; Kalb, Robert G.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Ludolph, Albert; Robberecht, Wim; Andersen, Peter M.; Nicholson, Garth A.; Blair, Ian P.; King, Oliver D.; Bonini, Nancy M.; Van Deerlin, Vivianna; Rademakers, Rosa; Mourelatos, Zissimos; Gitler, Aaron D.

2011-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of these genes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila, with the ALS-linked variants having a more severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery. PMID:22065782

Differential X-ray phase contrast tomography of Alzheimer plaques in mouse models: perspectives for drug development and clinical imaging techniques

NASA Astrophysics Data System (ADS)

Pinzer, B. R.; Cacquevel, M.; Modregger, P.; Thuering, T.; Stampanoni, M.

2013-05-01

Alzheimer's disease (AD) is a looming threat on an ever-ageing population, with devastating effects on the human intellect. A particular characteristic lesion — the extracellular amyloid plaque — accumulates in the brain of AD patients during the course of the disease, and could therefore be used to monitor the progression of the disease, years before the first neurological symptoms appear. In addition, strategies for drug intervention in AD are often based on amyloid reduction, since amyloid plaques are hypothesized to be involved in a chain of reactions leading to the death of neurons. Developments in both fields would benefit from a microscopic technique that is capable of single plaque imaging, ideally in 3D. While such a non-destructive, single-plaque imaging technique does not yet exist for humans, it has been recently shown that synchrotron based differential X-ray phase contrast imaging can be used to visualize individual plaques at μm resolution in mouse models of AD ex-vivo. This method, which relies on a grating interferometer to measure refraction angles induced by fluctuations in the refractive index, yields a precise three-dimensional distribution of single plaques. These data could not only improve the understanding of the evolution of AD or the effectiveness of drugs, but could also help to improve reliable markers for current and future non-invasive clinical imaging techniques. In particular, validation of PET markers with small animal models could be rapidly carried out by co-registration of PET and DPC signals.

Myelination, oligodendrocytes, and serious mental illness.

PubMed

Haroutunian, V; Katsel, P; Roussos, P; Davis, K L; Altshuler, L L; Bartzokis, G

2014-11-01

Historically, the human brain has been conceptually segregated from the periphery and further dichotomized into gray matter (GM) and white matter (WM) based on the whitish appearance of the exceptionally high lipid content of the myelin sheaths encasing neuronal axons. These simplistic dichotomies were unfortunately extended to conceptually segregate neurons from glia, cognition from behavior, and have been codified in the separation of clinical and scientific fields into medicine, psychiatry, neurology, pathology, etc. The discrete classifications have helped obscure the importance of continual dynamic communication between all brain cell types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2) cells) as well as between brain and periphery through multiple signaling systems. The signaling systems range from neurotransmitters to insulin, angiotensin, and multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help integrate metabolism, inflammation, and myelination processes and orchestrate the development, plasticity, maintenance, and repair that continually optimize function of neural networks. A more comprehensive, evolution-based, systems biology approach that integrates brain, body, and environmental interactions may ultimately prove more fruitful in elucidating the complexities of human brain function. The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems-level understanding of the interdependent age-related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases. Herein we highlight the role of glia, especially the most recently evolved oligodendrocytes and the myelin they produce, in achieving and maintaining optimal brain function. The human brain undergoes exceptionally protracted and pervasive myelination (even throughout its GM) and can thus achieve and maintain the rapid conduction and synchronous timing of neural networks on which optimal function depends. The continuum of increasing myelin vulnerability resulting from the human brain's protracted myelination underlies underappreciated communalities between different disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD). These shared vulnerabilities also expose significant yet underexplored opportunities for novel treatment and prevention approaches that have the potential to considerably reduce the tremendous burden of neuropsychiatric disease. © 2014 Wiley Periodicals, Inc.

Adult somatic stem cells in the human parasite Schistosoma mansoni.

PubMed

Collins, James J; Wang, Bo; Lambrus, Bramwell G; Tharp, Marla E; Iyer, Harini; Newmark, Phillip A

2013-02-28

Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.

The Decade of Education for Sustainable Development: A Perspective from Australia

ERIC Educational Resources Information Center

Lang, Josephine R.

2005-01-01

Amidst Australia's background of ecological devastation there is hope as people and their communities search for ways to re-think and revision their future, moving ever so slowly towards sustainability. For the author, sustainability is the intersection where humanity consciously engages with the ecological systems in ways to ensure all life is…

Handling Sexuality Concerns in Women with Gynecological Cancer: Egyptian Nurse's Knowledge and Attitudes

ERIC Educational Resources Information Center

Mansour, Suzan E.; Mohamed, Hanan E.

2015-01-01

Sexuality is an important part of normal human functioning. Gynecological cancer diagnosis and treatment has devastating effect on Sexual issues. Study aim was to investigate Oncology Nurses knowledge and attitudes in Relation to Provision of Sexual Health Care to Women Diagnosed with Gynecological Cancer. The study setting was conducted at…

Digitizing Ethiopic: Coding for Linguistic Continuity in the Face of Digital Extinction

ERIC Educational Resources Information Center

Zaugg, Isabelle Alice

2017-01-01

Despite the growing sophistication of digital technologies, it appears they are contributing to language extinction on a par with devastating losses in biodiversity. With language extinction comes loss of identity, inter-generational cohesion, culture, and a global wealth of knowledge to address future problems facing humanity. Linguists estimate…

Hurricane Ike versus an Atomic Bomb

ERIC Educational Resources Information Center

Pearson, Earl F.

2013-01-01

The destructive potential of one of nature's most destructive forces, the hurricane, is compared to one of human's most destructive devices, an atomic bomb. Both can create near absolute devastation at "ground zero". However, how do they really compare in terms of destructive energy? This discussion compares the energy, the…

Five Essential Elements of Crisis Intervention for Communities and Schools When Responding to Technological Disasters

ERIC Educational Resources Information Center

Sulkowski, Michael L.; Lazarus, Philip J.

2013-01-01

Technological disasters result from human error, negligence, or limitations in perceiving and reducing risk. They are a form of manmade disaster that exerts a devastating effect on impacted individuals, communities, and ecosystems. Because of their negative impacts, technological disasters often erode community connectedness, undermine adaptive…

The HPLC-Fluorescence Detection of Coumarins in ‘Hamlin’ Sweet Orange and ‘Marsh’ Grapefruit Leaf Cankers

USDA-ARS?s Scientific Manuscript database

Canker is a devastating disease for the citrus fresh fruit market and is caused by the pathogenic bacterium Xanthomonas citri var. citri (Xcc). Infection occurs by bacterial penetration through physical damage of leaves, peel and stems, and also by bacterial entry through the stomates of these photo...

Wheat transcription factor TaWRKY70 is positively involved in high-temperature seedling-plant resistance to Puccinia striiformis f. sp. tritici

USDA-ARS?s Scientific Manuscript database

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease of wheat (Triticum aestivum) worldwide. Wheat high-temperature seedling-plant (HTSP) resistance to Pst is non-race-specific and durable. WRKY transcription factors have proven to play important roles in ...

Validation of a major quantitative trait locus associated with host response to experimental infection with Porcine Reproductive and Respiratory Syndrome virus

USDA-ARS?s Scientific Manuscript database

Infectious diseases are costly to the swine industry and porcine reproductive and respiratory syndrome virus (PRRSV) is the most devastating. In earlier work, a quantitative trait locus associated with resistance/susceptibility to PRRSV was identified on Sus scrofa chromosome 4 (SSC4) using ~560 exp...

Genome Sequences of 19 Novel Erwinia amylovora Bacteriophages.

PubMed

Esplin, Ian N D; Berg, Jordan A; Sharma, Ruchira; Allen, Robert C; Arens, Daniel K; Ashcroft, Cody R; Bairett, Shannon R; Beatty, Nolan J; Bickmore, Madeline; Bloomfield, Travis J; Brady, T Scott; Bybee, Rachel N; Carter, John L; Choi, Minsey C; Duncan, Steven; Fajardo, Christopher P; Foy, Brayden B; Fuhriman, David A; Gibby, Paul D; Grossarth, Savannah E; Harbaugh, Kala; Harris, Natalie; Hilton, Jared A; Hurst, Emily; Hyde, Jonathan R; Ingersoll, Kayleigh; Jacobson, Caitlin M; James, Brady D; Jarvis, Todd M; Jaen-Anieves, Daniella; Jensen, Garrett L; Knabe, Bradley K; Kruger, Jared L; Merrill, Bryan D; Pape, Jenny A; Payne Anderson, Ashley M; Payne, David E; Peck, Malia D; Pollock, Samuel V; Putnam, Micah J; Ransom, Ethan K; Ririe, Devin B; Robinson, David M; Rogers, Spencer L; Russell, Kerri A; Schoenhals, Jonathan E; Shurtleff, Christopher A; Simister, Austin R; Smith, Hunter G; Stephenson, Michael B; Staley, Lyndsay A; Stettler, Jason M; Stratton, Mallorie L; Tateoka, Olivia B; Tatlow, P J; Taylor, Alexander S; Thompson, Suzanne E; Townsend, Michelle H; Thurgood, Trever L; Usher, Brittian K; Whitley, Kiara V; Ward, Andrew T; Ward, Megan E H; Webb, Charles J; Wienclaw, Trevor M; Williamson, Taryn L; Wells, Michael J; Wright, Cole K; Breakwell, Donald P; Hope, Sandra; Grose, Julianne H

2017-11-16

Erwinia amylovora is the causal agent of fire blight, a devastating disease affecting some plants of the Rosaceae family. We isolated bacteriophages from samples collected from infected apple and pear trees along the Wasatch Front in Utah. We announce 19 high-quality complete genome sequences of E. amylovora bacteriophages. Copyright © 2017 Esplin et al.

Variation in the AvrSr35 effector determines Sr35 resistance against wheat stem rust race Ug99

USDA-ARS?s Scientific Manuscript database

Puccinia graminis f. sp. tritici (Pgt) causes wheat stem rust, a devastating fungal disease. The Sr35 resistance gene confers immunity against this pathogen’s most virulent races, including Ug99. We used the comparative whole genome sequencing of chemically mutagenized and natural Pgt isolates to id...

Characterization and purification of proteins suitable for the production of antibodies against ‘Ca. Liberibacter asiaticus’

USDA-ARS?s Scientific Manuscript database

The citrus disease huanglongbing (HLB), which is caused by ‘Candidatus Liberibacter asiaticus’ (CaLas), is one of the most devastating pathogens of citrus, and with no effective method of control, poses a serious threat to citrus production throughout the world. In a previous study we described the...

Induction of humoral immune response to multiple recombinant rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

USDA-ARS?s Scientific Manuscript database

Background: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiologic agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect fee...

First detection of bat white-nose syndrome in western North America

Treesearch

Jeffrey M. Lorch; Jonathan M. Palmer; Daniel L. Lindner; Anne E. Ballmann; Kyle G. George; Kathryn Griffin; Susan Knowles; John R. Huckabee; Katherine H. Haman; Christopher D. Anderson; Penny A. Becker; Joseph B. Buchanan; Jeffrey T. Foster; David S. Blehert; Katherine McMahon

2016-01-01

White-nose syndrome (WNS) is an emerging fungal disease of bats caused by Pseudogymnoascus destructans. Since it was first detected near Albany, NY, in 2006, the fungus has spread across eastern North America, killing unprecedented numbers of hibernating bats. The devastating impacts of WNS on Nearctic bat species are attributed to the likely...

Biological control of Asian citrus psyllid (Diaphorina citri) in Florida by the parasitoid Tamarixia radiata in urban plantings of orange jasmine

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid is an important invasive citrus pest in the United States because it vectors a bacterium responsible for a devastating disease of citrus known as huanglongbing. A parasitoid of the psyllid, Tamarixia radiata (Hymenoptera: Eulophidae), was imported from Southeast Asia and re...

A Morpholino Strategy to Assess TSC Gene Function in Zebrafish

DTIC Science & Technology

2006-11-01

ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...devastating autosomal dominant disease that results in severe neurological symptoms including mental retardation, autism , and seizures (DiMario, 2004

First report of brown rot on apple fruit caused by Monilinia fructicola in the United States

USDA-ARS?s Scientific Manuscript database

Brown rot, caused by Monilinia fructicola (G. Wint.) Honey, is the most devastating disease of stone fruits in North America resulting in significant economic losses. The fungus has been recently reported to cause pre and postharvest brown rot on apple fruit in Germany, Italy, and Serbia. However, M...

Why Biosecurity Matters: Students' Knowledge of Biosecurity and Implications for Future Engagement with Biosecurity Initiatives

ERIC Educational Resources Information Center

Ram, Rajesh; France, Bev; Birdsall, Sally

2016-01-01

Background: Research on biosecurity is important as New Zealand's agricultural export-driven economy is susceptible to biosecurity threats. Because New Zealand is reliant on the primary industries to drive its economy, bovine diseases such as foot and mouth could have a devastating effect on the economy. Purpose: Making sure that the general…

The efficacy of recombinant turkey herpesvirus vaccines targeting the H5 of highly pathogenic avian influenza virus from the 2014/2015 North American outbreak

USDA-ARS?s Scientific Manuscript database

The outbreak of highly pathogenic avian influenza virus in North American poultry during 2014 and 2015 demonstrated the devastating effects of the disease and highlighted the need for effective emergency vaccine prevention and control strategies targeted at currently circulating strains. This study...

MontanideTM Gel01 ST adjuvant enhances PRRS modified live vaccine efficacy by regulating porcine humoral and cellular immune responses

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity against PRRSV infection in piglets when used in combination with PRRS modified live vac...

Response of swamp bay, Persea palustris , and redbay, P. borbonia , to Raffaelea spp. isolated from Xyleborus glabratus

Treesearch

T. J. Dreaden; A. S. Campbell; C. A. Gonzalez-Benecke; R. C. Ploetz; J. A. Smith

2016-01-01

Laurel wilt is a devastating invasive disease of members of the Lauraceae plant family. It is caused by the fungus Raffaelea lauricola, which is a nutritional symbiont of its ambrosia beetle vector, Xyleborus glabratus. In the United States, six Raffaelea spp., in addition to R. lauricola...

Identification of wheat gene Sr35 that confers resistance to Ug99 stem rust race group

USDA-ARS?s Scientific Manuscript database

Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt) is a devastating disease that can cause severe yield losses. A new Pgt race designated Ug99 has overcome most of the widely used resistance genes and is spreading through Africa and Asia threatening major wheat production areas. We re...

Exposing Cancer Cells' Secret Aides to Spread Disease to Distant Sites | Center for Cancer Research

Cancer.gov

Researchers are shedding new light on the way cancer spreads from the primary organ to distant sites in the body, a process called metastasis. The assault of metastatic tumors on vital organs too frequently results in death, and until recently, little was known about the molecular mechanisms governing this devastating phenomenon.

Long-term changes in fusiform rust incidence in the southeastern United States

Treesearch

KaDonna C. Randolph; Ellis B. Cowling; Dale A. Starkey

2015-01-01

Fusiform rust is the most devastating disease of slash pine (Pinus elliottii) and loblolly pine (Pinus taeda) in the southeastern United States. Since the 1970s, the USDA Forest Service Forest Inventory and Analysis (FIA) Program has assessed fusiform rust incidence on its network of ground plots in 13 states across the...

An interspecific barberry hybrid enables genetic dissection of non-host resistance to the wheat stem rust pathogen

USDA-ARS?s Scientific Manuscript database

Stem rust, caused by the macrocyclic fungal pathogen Puccinia graminis (Pg), is one of the most devastating diseases of wheat and other small grains globally; and the emergence of new stem rust races virulent on deployed resistance genes brings urgency to the discovery of more durable sources of gen...

Conservation status of a threatened tree species: establishing a baseline for restoration of Juglans cinerea L

Treesearch

Amanda M. Parks; Michael A. Jenkins; Keith E. Woeste; Michael E. Ostry

2013-01-01

To mitigate the loss of native tree species threatened by non-native pathogens, managers need to better understand the conservation status of remaining populations and the conditions that favor successful regeneration. Populations of Juglans cinerea L. (butternut), a wide-ranging riparian species, have been devastated by butternut canker, a disease...

The intricate mechanisms of neurodegeneration in prion diseases

PubMed Central

Soto, Claudio; Satani, Nikunj

2010-01-01

Prion diseases are a group of infectious neurodegenerative diseases with an entirely novel mechanism of transmission, involving a protein-only infectious agent that propagates the disease by transmitting protein conformational changes. The disease results from extensive and progressive brain degeneration. The molecular mechanisms involved in neurodegeneration are not entirely known but involve multiple processes operating simultaneously and synergistically in the brain, including spongiform degeneration, synaptic alterations, brain inflammation, neuronal death and the accumulation of protein aggregates. Here, we review the pathways implicated in prion-induced brain damage and put the pieces together into a possible model of neurodegeneration in prion disorders. A more comprehensive understanding of the molecular basis of brain degeneration is essential to develop a much needed therapy for these devastating diseases. PMID:20889378

Hidradenitis suppurativa - Management, comorbidities and monitoring.

PubMed

Vekic, Dunja A; Cains, Geoffrey D

2017-01-01

Hidradenitis suppurativa (HS) is a chronic inflammatory disease presenting in intertriginous areas. HS is associated with a number of disease-modifying comorbidities, including metabolic syndrome and androgen dysfunction, and smoking. This review provides a synopsis of the aetiology and diagnosis of HS, and an overview of management for this often devastating disease. The clinical course and disease severity of HS are variable among patients. HS has profound physical and psychological consequences that affect patients' quality of life. Effective treatment is now a realistic goal, but needs to be combined with treatment of the comorbidities and psyche. Evidence-based management guidelines have been established for the management of this disease. General practitioners play a pivotal role in the holistic treatment of this disease.

Canine Disorder Mirrors Human Disease: Exonic Deletion in HES7 Causes Autosomal Recessive Spondylocostal Dysostosis in Miniature Schnauzer Dogs

PubMed Central

Willet, Cali E.; Makara, Mariano; Reppas, George; Tsoukalas, George; Malik, Richard; Haase, Bianca; Wade, Claire M.

2015-01-01

Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of P raw = 4.759e-36 (genome-wide significant). Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses. PMID:25659135

Structural Insights into SraP-Mediated Staphylococcus aureus Adhesion to Host Cells

PubMed Central

Zhang, Juan; Wang, Lei; Bai, Xiao-Hui; Zhang, Shi-Jie; Ren, Yan-Min; Li, Na; Zhang, Yong-Hui; Zhang, Zhiyong; Gong, Qingguo; Mei, Yide; Xue, Ting; Zhang, Jing-Ren; Chen, Yuxing; Zhou, Cong-Zhao

2014-01-01

Staphylococcus aureus, a Gram-positive bacterium causes a number of devastating human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. S. aureus SraP, a surface-exposed serine-rich repeat glycoprotein (SRRP), is required for the pathogenesis of human infective endocarditis via its ligand-binding region (BR) adhering to human platelets. It remains unclear how SraP interacts with human host. Here we report the 2.05 Å crystal structure of the BR of SraP, revealing an extended rod-like architecture of four discrete modules. The N-terminal legume lectin-like module specifically binds to N-acetylneuraminic acid. The second module adopts a β-grasp fold similar to Ig-binding proteins, whereas the last two tandem repetitive modules resemble eukaryotic cadherins but differ in calcium coordination pattern. Under the conditions tested, small-angle X-ray scattering and molecular dynamic simulation indicated that the three C-terminal modules function as a relatively rigid stem to extend the N-terminal lectin module outwards. Structure-guided mutagenesis analyses, in addition to a recently identified trisaccharide ligand of SraP, enabled us to elucidate that SraP binding to sialylated receptors promotes S. aureus adhesion to and invasion into host epithelial cells. Our findings have thus provided novel structural and functional insights into the SraP-mediated host-pathogen interaction of S. aureus. PMID:24901708

Small RNA Profiling Reveals Phosphorus Deficiency as a Contributing Factor in Symptom Expression for Citrus Huanglongbing Disease

PubMed Central

Zhao, Hongwei; Sun, Ruobai; Jin, Hailing

2013-01-01

Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus ‘Candidatus Liberibacter’ (Ca. L.). Powerful diagnostic tools and management strategies are desired to control HLB. Host small RNAs (sRNA) play a vital role in regulating host responses to pathogen infection and are used as early diagnostic markers for many human diseases, including cancers. To determine whether citrus sRNAs regulate host responses to HLB, sRNAs were profiled from Citrus sinensis 10 and 14 weeks post grafting with Ca. L. asiaticus (Las)-positive or healthy tissue. Ten new microRNAs (miRNAs), 76 conserved miRNAs, and many small interfering RNAs (siRNAs) were discovered. Several miRNAs and siRNAs were highly induced by Las infection, and can be potentially developed into early diagnosis markers of HLB. miR399, which is induced by phosphorus starvation in other plant species, was induced specifically by infection of Las but not Spiroplasma citri that causes citrus stubborn—a disease with symptoms similar to HLB. We found a 35% reduction of phosphorus in Las-positive citrus trees compared to healthy trees. Applying phosphorus oxyanion solutions to HLB-positive sweet orange trees reduced HLB symptom severity and significantly improved fruit production during a 3-year field trial in south-west Florida. Our molecular, physiological, and field data suggest that phosphorus deficiency is linked to HLB disease symptomology. PMID:23292880

Environmental and social influences on emerging infectious diseases: past, present and future.

PubMed Central

McMichael, A J

2004-01-01

During the processes of human population dispersal around the world over the past 50 000-100 000 years, along with associated cultural evolution and inter-population contact and conflict, there have been several major transitions in the relationships of Homo sapiens with the natural world, animate and inanimate. Each of these transitions has resulted in the emergence of new or unfamiliar infectious diseases.The three great historical transitions since the initial advent of agriculture and livestock herding, from ca. 10 000 years ago, occurred when: (i) early agrarian-based settlements enabled sylvatic enzootic microbes to make contact with Homo sapiens; (ii) early Eurasian civilizations (such as the Greek and Roman empires, China and south Asia) came into military and commercial contact, ca. 3000-2000 years ago, swapping their dominant infections; and (iii) European expansionism, over the past five centuries, caused the transoceanic spread of often lethal infectious diseases. This latter transition is best known in relation to the conquest of the Americas by Spanish conquistadores, when the inadvertent spread of measles, smallpox and influenza devastated the Amerindian populations.Today, we are living through the fourth of these great transitional periods. The contemporary spread and increased lability of various infectious diseases, new and old, reflect the combined and increasingly widespread impacts of demographic, environmental, behavioural, technological and other rapid changes in human ecology. Modern clinical medicine has, via blood transfusion, organ transplantation, and the use of hypodermic syringes, created new opportunities for microbes. These have contributed to the rising iatrogenic problems of hepatitis C, HIV/AIDS and several other viral infections. Meanwhile, the injudicious use of antibiotics has been a rare instance of human action actually increasing 'biodiversity'.Another aspect of this fourth transition is that modern hyper-hygienic living restricts microbial exposure in early life. This, in the 1950s, may have contributed to an epidemic of more serious, disabling, poliomyelitis, affecting older children than those affected in earlier, more endemic decades. As with previous human-microbe transitions, a new equilibrial state may lie ahead. However, it certainly will not entail a world free of infectious diseases. Any mature, sustainable, human ecology must come to terms with both the need for, and the needs of, the microbial species that help to make up the interdependent system of life on Earth. Humans and microbes are not "at war"; rather, both parties are engaged in amoral, self-interested, coevolutionary struggle. We need to understand better, and therefore anticipate, the dynamics of that process. PMID:15306389

Regional and international approaches on prevention and control of animal transboundary and emerging diseases.

PubMed

Domenech, J; Lubroth, J; Eddi, C; Martin, V; Roger, F

2006-10-01

Transboundary animal diseases pose a serious risk to the world animal agriculture and food security and jeopardize international trade. The world has been facing devastating economic losses from major outbreaks of transboundary animal diseases (TADs) such as foot-and-mouth disease, classical swine fever, rinderpest, peste des petits ruminants (PPR), and Rift Valley fever. Lately the highly pathogenic avian influenza (HPAI) due to H5N1 virus, has become an international crisis as all regions around the world can be considered at risk. In the past decades, public health authorities within industrialized countries have been faced with an increasing number of food safety issues. The situation is equally serious in developing countries. The globalization of food (and feed) trade, facilitated by the liberalization of world trade, while offering many benefits and opportunities, also represents new risks. The GF-TADs Global Secretariat has carried out several regional consultations for the identification of priority diseases and best ways for their administration, prevention and control. In the questionnaires carried out and through the consultative process, it was noted that globally, FMD was ranked as the first and foremost priority. Rift Valley fever, and today highly pathogenic avian influenza, are defined as major animal diseases which also affect human health. PPR and CBPP, a disease which is particularly serious in Africa and finally, African swine fever (ASF) and classical swine fever (CSF) are also regionally recognised as top priorities on which the Framework is determined to work. The FAO philosophy--shared by the OIE--embraces the need to prevent and control TADs and emerging diseases at their source, which is most of the time in developing countries. Regional and international approaches have to be followed, and the FAO and OIE GF-TADs initiative provides the appropriate concepts and objectives as well as an organizational framework to link international and regional organizations at the service of their countries to better prevent and control the risks on animal and human health and the economic impact of TADs and emerging animal diseases.

Antifungal activity of plant extracts against Aspergillus niger and Rhizopus stolonifer.

PubMed

Surapuram, Venkatasaichaitanya; Setzer, William N; McFeeters, Robert L; McFeeters, Hana

2014-11-01

Despite recent advances in antifungal development, fungi remain a devastating threat to human health and compromise viability of the food supply. Plant based antimicrobials represent a vast untapped source with tremendous potential. Herein we present the antifungal properties of more than 50 plant extracts against two important human and agricultural pathogens, Aspergillus niger and Rhizopus stolonifer. Multiple extracts exhibit promising MIC values of less than 100 μg/mL and are reported for both fungal species.

Detection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage▿ †

PubMed Central

Loh, Joy; Zhao, Guoyan; Presti, Rachel M.; Holtz, Lori R.; Finkbeiner, Stacy R.; Droit, Lindsay; Villasana, Zoilmar; Todd, Collin; Pipas, James M.; Calgua, Byron; Girones, Rosina; Wang, David; Virgin, Herbert W.

2009-01-01

The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the asfarvirus family but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among asfarviruses than previously thought and raises the possibility that human infection by asfarviruses may occur. PMID:19812170

Aloesin as a medical food ingredient for systemic oxidative stress of diabetes

PubMed Central

Yimam, Mesfin; Brownell, Lidia; Jia, Qi

2015-01-01

Diabetes is a chronic disease that requires a long term management where oxidative stress plays a pivotal role in disease progression and intensifying secondary complications. In spite of all the research on diabetes and recent advances in diabetes treatments, the reality is that there is no cure for diabetes and its devastating complications. While currently available anti-diabetic therapies are effective in reducing blood glucose level, they are not without associated side effects when they are used for a long term applications. As a result, physicians and patients are inclining more towards to a safer therapy with less serious side effects in the form of medicinal foods and botanical alternatives that are suitable for chronic usage. Aloesin, an Aloe chromone, has previously been formulated with an aloe polysaccharide to give a composition called Loesyn, where it showed significant impact in reducing glycosylated hemoglobin, fasting blood glucose, fructosamine and plasma insulin level in humans. Radical scavenging activities of chromones and polysaccharides from Aloe have also been reported. Here we rationalize the relevance of use of Aloesin alone or in a standardized blend with Aloe polysaccharides, as a potential medical food to manage systemic oxidative stress and/or high blood glucose of diabetes. PMID:26265996

Metals and Alzheimer’s Disease: How Far Have We Come in the Clinic?

PubMed Central

Adlard, Paul A.; Bush, Ashley I.

2018-01-01

It is estimated that by the year 2050 there will be more than 1.5 billion people globally over the age of 65 years. Aging is associated with changes to a number of different cellular processes which are driven by a variety of factors that contribute to the characteristic decline in function that is seen across multiple physiological domains/tissues in the elderly (including the brain). Importantly, aging is also the primary risk factor for the development of neurodegenerative disorders such as Alzheimer’s disease. As such, there is an urgent need to provide a greater understanding of both the pathogenesis and treatment of these devastating neurodegenerative disorders. One of the key cellular processes that becomes dysregulated with age and participates both directly and indirectly in age-related dysfunction, is metal homeostasis and the neurochemistry of metalloproteins, the basic science of which has been extensively reviewed in the past. In this review, we will focus on the human clinical intervention trials that have been conducted over approximately the last four decades that have attempted to establish the efficacy of targeting metal ions in the treatment of AD. PMID:29562528

Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri.

PubMed

Baig, Abdul Mannan

2016-08-17

Naegleria fowleri causes one of the most devastating necrotic meningoencephalitis in humans. The infection caused by this free-living amoeba is universally fatal within a week of onset of the signs and symptoms of the disease called primary amoebic meningoencephalitis (PAM). In all the affected patients, there is always a history of entry of water into the nose. Even though the diagnostic and treatment protocols have been revised and improved, the obstinate nature of the disease can be gauged by the fact that the mortality rate has persisted around ∼95% over the past 60 years. Some of the unanswered questions regarding PAM are is there a neurochemical basis of the chemotaxis of N. fowleri to the brain? What immune evasion means occurs preceding the neurotropic invasion? What is the contribution of the acute inflammatory response in the fatal cases? Can a combination of anti-amoebic drugs with antagonism of the acute inflammation help save the patient's life? As prevention remains the most valuable safeguard against N. fowleri, a quicker diagnosis, better understanding of the pathogenesis of PAM coupled with testing of newer and safer drugs could improve the chances of survival in patients affected with PAM.

A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles Protects Nonhuman Primates from Lethal Ebola Virus Challenge.

PubMed

Domi, Arban; Feldmann, Friederike; Basu, Rahul; McCurley, Nathanael; Shifflett, Kyle; Emanuel, Jackson; Hellerstein, Michael S; Guirakhoo, Farshad; Orlandi, Chiara; Flinko, Robin; Lewis, George K; Hanley, Patrick W; Feldmann, Heinz; Robinson, Harriet L; Marzi, Andrea

2018-01-16

Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013-2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV). GP and VP40 form EBOV-like particles and elicit protective immune responses. In this study, we report 100% protection against lethal EBOV infection in guinea pigs after prime/boost vaccination with MVA-EBOV. Furthermore, this MVA-EBOV protected macaques from lethal disease after a single dose or prime/boost vaccination. The vaccine elicited a variety of antibody responses to both antigens, including neutralizing antibodies and antibodies with antibody-dependent cellular cytotoxic activity specific for GP. This is the first report that a replication-deficient MVA vector can confer full protection against lethal EBOV challenge after a single dose vaccination in macaques.

Phytomedicines and Nutraceuticals: Alternative Therapeutics for Sickle Cell Anemia

PubMed Central

Imaga, Ngozi Awa

2013-01-01

Sickle cell anemia is a genetically inherited disease in which the “SS” individual possesses an abnormal beta globin gene. A single base substitution in the gene encoding the human β-globin subunit results in replacement of β6 glutamic acid by valine, leading to the devastating clinical manifestations of sickle cell disease. This substitution causes drastic reduction in the solubility of sickle cell hemoglobin (HbS) when deoxygenated. Under these conditions, the HbS molecules polymerize to form long crystalline intracellular mass of fibers which are responsible for the deformation of the biconcave disc shaped erythrocyte into a sickle shape. First-line clinical management of sickle cell anemia include, use of hydroxyurea, folic acid, amino acids supplementation, penicillinprophylaxis, and antimalarial prophylaxis to manage the condition and blood transfusions to stabilize the patient's hemoglobin level. These are quite expensive and have attendant risk factors. However, a bright ray of hope involving research into antisickling properties of medicinal plants has been rewarding. This alternative therapy using phytomedicines has proven to not only reduce crisis but also reverse sickling (in vitro). The immense benefits of phytomedicines and nutraceuticals used in the management of sickle cell anemia are discussed in this paper. PMID:23476125

The role of oxidative stress in Huntington's disease: are antioxidants good therapeutic candidates?

PubMed

Gil-Mohapel, Joana; Brocardo, Patricia S; Christie, Brian R

2014-04-01

Huntington's disease (HD) is the most common polyglutamine neurodegenerative disorder in humans, and is caused by a mutation of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. Although abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, and there, predominantly in the striatum and cortex. The mechanisms that account for this selective neuronal death are multifaceted in nature and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and DNA) might play important roles. Over time, this can result in the death of the affected neuronal populations. In this review article we present an overview of the preclinical and clinical studies that have indicated a link between oxidative stress, neurodegeneration, and cell death in HD. We also discuss how changes in ROS production affect neuronal survival, highlighting the evidence for the use of antioxidants including essential fatty acids, coenzyme Q10, and creatine, as potential therapeutic strategies for the treatment of this devastating neurodegenerative disorder.

Current controversies in the USA regarding vaccine safety.

PubMed

Chatterjee, Archana; O'Keefe, Catherine

2010-05-01

As a result of the vaccines discovered in the 20th Century, parents and many healthcare providers of the 21st Century have limited or no experience with the devastating effects of diseases such as polio, smallpox or measles. Fear of disease has shifted to concerns regarding vaccine safety. Scientific evidence has refuted many of the misconceptions regarding vaccine safety; however, parental refusal of vaccines is increasing. Here we review six of the most prevalent controversies surrounding vaccine safety: the proposed causal relationship between receipt of the measles-mumps-rubella vaccine and autism; thimerosal as a potential trigger for autism; religious objection based on some vaccine viruses being grown in cell lines from aborted fetal tissues; parental worries that use of the human papillomavirus vaccine may lead to youth promiscuity; fears regarding the purported association between pertussis vaccination and adverse neurological outcomes; and concerns regarding too many vaccines overloading or weakening the infant immune system. Healthcare providers are ideally positioned to correct these misconceptions, but they must recognize and acknowledge parents' concerns, educate themselves on the latest scientific research that addresses these, and dedicate sufficient time to discuss vaccine safety with worried parents.

Apartheid medicine. Health and human rights in South Africa.

PubMed

Nightingale, E O; Hannibal, K; Geiger, H J; Hartmann, L; Lawrence, R; Spurlock, J

Human rights and health care under apartheid in South Africa were studied. Human rights violations, such as detention without charge or trial, assault and torture in police custody, and restriction orders, have had devastating effects on the health of persons experiencing them. These violations have occurred in the context of a deliberate policy of discriminatory health care favoring the white minority over the black majority. South Africa's medical societies have had mixed responses to the health problems raised by human rights violations and inequities in the health care system. The amelioration of health care for all and prevention of human rights violations depend on ending apartheid and discrimination and greater government attention to these problems.

Software support for Huntingtons disease research.

PubMed

Conneally, P M; Gersting, J M; Gray, J M; Beidleman, K; Wexler, N S; Smith, C L

1991-01-01

Huntingtons disease (HD) is a hereditary disorder involving the central nervous system. Its effects are devastating, to the affected person as well as his family. The Department of Medical and Molecular Genetics at Indiana University (IU) plays an integral part in Huntingtons research by providing computerized repositories of HD family information for researchers and families. The National Huntingtons Disease Research Roster, founded in 1979 at IU, and the Huntingtons Disease in Venezuela Project database contain information that has proven to be invaluable in the worldwide field of HD research. This paper addresses the types of information stored in each database, the pedigree database program (MEGADATS) used to manage the data, and significant findings that have resulted from access to the data.

Idiopathic intracranial hypertension and sickle cell disease: two case reports.

PubMed

Segal, Laura; Discepola, Marino

2005-12-01

Two patients with sickle cell disease presented with headaches and visual disturbances, typical complaints of this disorder. However, prompt diagnosis of idiopathic intracranial hypertension and initiation of medical therapy lead to improved symptoms and restored vision. Ophthalmologists should consider sickle cell disease to be an independent risk factor for idiopathic intracranial hypertension when a patient is being assessed for visual disturbances. Although a rare condition, idiopathic intracranial hypertension has several key signs useful in establishing a diagnosis. It is critical to recognize the warning signs and symptoms to prevent devastating ophthalmologic complications. We report the first cases of idiopathic intracranial hypertension in patients with the novel Quebec-Chori beta-chain variant of sickle cell disease.

Christian Education, White Supremacy, and Humility in Formational Agendas

ERIC Educational Resources Information Center

Turpin, Katherine

2017-01-01

Christian education served as a tool of White supremacy that played a central role in the devastation of millions of human lives throughout the colonial era of Western expansion. An adequate account of how Christian education paired with colonial imperatives helps to identify where the legacy of White supremacy and imperial domination lives on in…

Open Dialogue Systems: Humanizing the Designs of Residential Mental Health Systems

ERIC Educational Resources Information Center

Harris, Charles

1977-01-01

Describes a devastating personal experience that led to a new awareness. Author still has no recollection of the head-on car wreck in which she was critically injured. She discusses the recovery process, especially the facilitative and inhibiting roles played by various people. Makes a plea for improvement in the training of health professionals.…

The Challenges for Sub-Saharan Africa. Sir John Crawford Memorial Lecture (1st, Washington, DC, November 1, 1985).

ERIC Educational Resources Information Center

McNamara, Robert S.

The economic crisis in Sub-Saharan Africa threatens to condemn an entire continent to human misery unless stronger action is taken to control population growth, reverse ecological devastation, eliminate distortions in domestic economic policies, and increase external development finance. Substantial increases in financial assistance to Africa are…

Pre-Layoff Intervention: A Response to Unemployment. Second Edition.

ERIC Educational Resources Information Center

Stone, Judson; And Others

Based on a program provided by a consortium of mental health centers in the Detroit, Michigan, area, this manual is intended to assist in the development and delivery of programs that allay or prevent the devastating human impact of plant shutdowns and large-scale layoffs. The guide focuses on delivery of programs that promote more effective use…

Structural imaging in premanifest and manifest Huntington disease.

PubMed

Scahill, Rachael I; Andre, Ralph; Tabrizi, Sarah J; Aylward, Elizabeth H

2017-01-01

Huntington disease (HD) neuropathology has a devastating effect on brain structure and consequently brain function; neuroimaging provides a means to assess these effects in gene carriers. In this chapter we first outline the unique utility of structural imaging in understanding HD and discuss some of the acquisition and analysis techniques currently available. We review the existing literature to summarize what we know so far about structural brain changes across the spectrum of disease from premanifest through to manifest disease. We then consider how these neuroimaging findings relate to patient function and nonimaging biomarkers, and can be used to predict disease onset. Finally we review the utility of imaging measures for assessment of treatment efficacy in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Elucidating the triggers, progression, and effects of Alzheimer's disease.

PubMed

Medeiros, Rodrigo; Chabrier, Meredith A; LaFerla, Frank M

2013-01-01

As the number of patients with Alzheimer's disease (AD) continues to rise, the need for efficacious therapeutics is becoming more and more urgent. Understanding the molecular relationship and interactions between Aβ and tau and their contribution to cognitive decline remain one of the most fundamental and unresolved questions in the AD field. Likewise, elucidating the initial triggers of disease pathology, as well as the impact of various factors such as stress and inflammation on disease progression, are equally important to fully understand this devastating disorder. Here we discuss recent studies that have illuminated the importance of key facilitators of disease progression using the 3xTg-AD and CaM/Tet-DTA mouse models, and suggest viable targets for ameliorating both molecular pathology and cognitive decline.

The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and fibroblasts in fibrotic lung disease

PubMed Central

Karmouty-Quintana, Harry; Cicko, Sanja; Ayata, Korcan; Zissel, Gernot; Goldmann, Torsten; Lungarella, Giuseppe; Ferrari, Davide; Di Virgilio, Francesco; Robaye, Bernard; Boeynaems, Jean-Marie; Blackburn, Michael R.; Idzko, Marco

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y2 in the context of fibrotic lung diseases. The concentration of different nucleotides was measured in the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals with bleomycin-induced pulmonary fibrosis. In addition expression of P2Y2 receptors by different cell types was determined. To investigate the functional relevance of P2Y2 receptors for the pathogenesis of the disease the bleomycin model of pulmonary fibrosis was used. Finally, experiments were performed in pursuit of the involved mechanisms. Compared to healthy individuals or vehicle treated animals, extracellular nucleotide levels in the BAL fluid were increased in patients with IPF and in mice after bleomycin administration, paralleled by a functional up-regulation of P2Y2R expression. Both bleomycin-induced inflammation and fibrosis were reduced in P2Y2R-deficient compared to wild type animals. Mechanistic studies demonstrated that recruitment of neutrophils into the lungs, proliferation and migration of lung fibroblasts as well as IL6 production are key P2Y2R mediated processes. Our results clearly demonstrate the involvement of P2Y2R subtypes in the pathogenesis of fibrotic lung diseases in humans and mice and hence support the development of selective P2Y2R antagonists for the treatment of IPF. PMID:28415591

Solidarity and AIDS: introduction.

PubMed

Krieger, N

1991-01-01

Perhaps more than any other disease in recent history, AIDS has taught a cruel and crucial lesson: the constraints on our response to this epidemic are as deep as our denial, as entrenched as the inequities that permeate our society, as circumscribed as our knowledge, and as unlimited as our compassion and our commitment to human rights. Elaborating on these themes, the final three articles in this Special Section on AIDS consider three widely divergent yet intimately connected topics: AIDS in Cuba, AIDS in Brazil, and global AIDS prevention in the 1990s. Together, they caution that if we persist in treating AIDS as a problem only of "others," no country will be spared the social and economic devastation that promises to be the cost of our contempt and our folly. Solidarity is not an option; it is a necessity. Without conscious recognition of the worldwide relationship between health, human rights, and social inequalities, our attempts to abate the spread of AIDS--and to ease the suffering that follows in its wake--most surely will fall short of our goals. Finally, as we mourn our dead, we must take to heart the words of Mother Jones, and "fight like hell for living." This is the politics of survival.

Totipotency, Pluripotency and Nuclear Reprogramming

NASA Astrophysics Data System (ADS)

Mitalipov, Shoukhrat; Wolf, Don

Mammalian development commences with the totipotent zygote which is capable of developing into all the specialized cells that make up the adult animal. As development unfolds, cells of the early embryo proliferate and differentiate into the first two lineages, the pluripotent inner cell mass and the trophectoderm. Pluripotent cells can be isolated, adapted and propagated indefinitely in vitro in an undifferentiated state as embryonic stem cells (ESCs). ESCs retain their ability to differentiate into cells representing the three major germ layers: endoderm, mesoderm or ectoderm or any of the 200+ cell types present in the adult body. Since many human diseases result from defects in a single cell type, pluripotent human ESCs represent an unlimited source of any cell or tissue type for replacement therapy thus providing a possible cure for many devastating conditions. Pluripotent cells resembling ESCs can also be derived experimentally by the nuclear reprogramming of somatic cells. Reprogrammed somatic cells may have an even more important role in cell replacement therapies since the patient's own somatic cells can be used for reprogramming thereby eliminating immune based rejection of transplanted cells. In this review, we summarize two major approaches to reprogramming: (1) somatic cell nuclear transfer and (2) direct reprogramming using genetic manipulations.

The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry world-wide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak and results in delayed elimination of virus from the host and inferior vaccine protection. PRR...

Use of multiple sequencing technologies to produce a high-quality genome of the fungus Pseudogymnoascus destructans, the causative agent of bat White-Nose syndrome

USGS Publications Warehouse

Drees, Kevin P.; Palmer, Jonathan M.; Sebra, Robert; Lorch, Jeffrey M.; Chen, Cynthia; Wu, ChengCang; Bok, Jin Woo; Keller, Nancy F.; Blehert, David; Cuomo, Christina A.; Linder, Daniel L.; Foster, Jeffrey T.

2016-01-01

White-Nose syndrome has recently emerged as one of the most devastating wildlife diseases recorded, causing widespread mortality in numerous bat species throughout eastern North America. Here, we present an improvised reference genome of the fungal pathogen Pseudogymnoascus destructans for use in comparative genomic studies.

Genome-wide association mapping for stripe rust (Puccinia striiformis F. sp. tritici) in US Pacific Northwest winter wheat (Triticum aestivum L.)

USDA-ARS?s Scientific Manuscript database

Stripe rust (Puccinia striiformis F. sp. tritici; also known as yellow rust) is a globally devastating disease of wheat (Triticum aestivum L.) and a major threat to wheat production in the US Pacific Northwest (PNW), therefore both adult plant and all-stage resistance have been introduced into the w...

HOPX1 Ea (Eop3) in Erwinia Amylovora functions as an avirulence gene in apple and is regulated by HRPL

USDA-ARS?s Scientific Manuscript database

Fire blight is a devastating disease of rosaceous plants caused by the Gram-negative bacterium E. amylovora. This pathogen delivers virulence proteins into host cells utilizing the Type-Three Secretion System (T3SS). Expression of the T3SS and associated substrates are activated by the alternative s...

Quantitative and qualitative stem rust resistance factors in barley are associated with transcriptional suppression of defense regulons

USDA-ARS?s Scientific Manuscript database

Stem rust (Puccinia graminis f. sp. tritici; Pgt) is a devastating fungal disease of wheat and barley. Pgt race TTKSK (isolate Ug99) is a serious threat to these Triticeae grain crops because resistance is rare. In barley, the complex Rpg-TTKSK locus on chromosome 5H is presently the only known so...

Wheat stripe rust resistance protein WKS1 reduces the ability of the thylakoid-associated ascorbate peroxidase to detoxify reactive oxygen species

USDA-ARS?s Scientific Manuscript database

Stripe rust is a devastating fungal disease of wheat caused by Puccinia striiformis f. sp. tritici(Pst). The WKS1 resistance gene has an unusual combination of serine/threonine kinase and START lipid-binding domains and confers partial resistance to Pst. Here we show that wheat plants transformed w...

Genotyping-by-sequencing uncovers the introgression alien segments associated with Sclerotinia basal stalk rot resistance from wild species—I. Helianthus argophyllus and H. petiolaris

USDA-ARS?s Scientific Manuscript database

Basal stalk rot (BSR), caused by Sclerotinia Sclerotiorum, is a devastating disease in sunflower worldwide. The progress of breeding for Sclerotinia BSR resistance has been hampered due to the lack of effective sources of resistance for cultivated sunflower. Our objective was to transfer BSR resista...

Mapping host-species abundance of three major exotic forest pests

Treesearch

Randall S. Morin; Andrew M. Liebhold; Eugene R. Luzader; Andrew J. Lister; Kurt W. Gottschalk; Daniel B. Twardus

2005-01-01

Periodically over the last century, forests of the Eastern United States devastated by invasive pests. We used existing data to predict the geographical extent of future damage from beech bark disease (BBD), hemlock woolly adelgid (HWA), and gypsy moth. The distributions of host species of these alien pests were mapped in 1-km2 cells by interpolating host basal area/ha...

Quantitative trait loci mapping of resistance to Fusarium oxysporum f. sp. niveum race 2 in Citrullus lanatus var. citroides using genotyping-by-sequencing

USDA-ARS?s Scientific Manuscript database

One of the most devastating watermelon diseases worldwide, Fusarium wilt, is caused by Fusarium oxysporum f. sp. niveum (Fon). Spread of the particularly virulent Fon race 2 in the United States, coupled with the lack of resistance in edible cultivars of the sweet cultivated watermelon Citrullus lan...

Mapping of Yr62 and a small effect QTL for high-temperature adult-plant resistance to stripe rust in spring wheat PI 192252

USDA-ARS?s Scientific Manuscript database

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease of wheat worldwide. Spring wheat germplasm PI 192252 showed a high level of high-temperature adult-plant (HTAP) resistance to stripe rust in germplasm evaluation over eight years in the State of Washington. ...

Tuber resistance and slow rotting characteristics of potato clones associated with the Solanaceae Coordinated Agricultural Project to the US-24 clonal lineage of Phytophthora infestans

USDA-ARS?s Scientific Manuscript database

Late blight, caused by Phytophthora infestans, is a devastating disease on potato worldwide and new lineages of the pathogen continue to develop in the U.S. Breeding for resistance is important for economic and environmental purposes. The Solanaceae Coordinated Agricultural Project (SolCAP) focuses ...

Bionomics of Asian citrus psyllid associated with orange jasmine hedges in Florida, with special reference to biological control by Tamarixia radiata

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid (ACP) is an important invasive citrus pest because it vectors a bacterium responsible for a devastating disease of citrus known as huanglongbing. Orange jasmine (Murraya paniculata) is a favored alternate ACP host plant and is widely grown as an ornamental plant in urban ar...

Use of Multiple Sequencing Technologies To Produce a High-Quality Genome of the Fungus Pseudogymnoascus destructans, the Causative Agent of Bat White-Nose Syndrome

PubMed Central

Sebra, Robert; Lorch, Jeffrey M.; Chen, Cynthia; Wu, Cheng-Cang; Bok, Jin Woo; Keller, Nancy P.; Blehert, David S.; Lindner, Daniel L.

2016-01-01

White-nose syndrome has recently emerged as one of the most devastating wildlife diseases recorded, causing widespread mortality in numerous bat species throughout eastern North America. Here, we present an improved reference genome of the fungal pathogen Pseudogymnoascus destructans for use in comparative genomic studies. PMID:27365344

Deletion of v-chiA from a baculovirus reduces horizontal transmission in the field

Treesearch

Vincent D' Amico; James Slavicek; John D. Podgwaite; Ralph Webb; Roger Fuester; Randall A. Peiffer

2013-01-01

Nucleopolyhedroviruses (NPVs) can initiate devastating disease outbreaks in populations of defoliating Lepidoptera, a fact that has been exploited for the purposes of biological control of some pest insects. A key part of the horizontal transmission process of NPVs is the degradation of the larval integument by virus-coded proteins called chitinases, such as V-CHIA...

Developing hazelnuts (Corylus spp.) with durable resistance to eastern filbert blight caused by Anisogramma anomala

Treesearch

Thomas J. Molnar; John Capik; Clayton W. Leadbetter; Ning Zhang; Guohong Cai; Bradley I. Hillman

2012-01-01

Eastern filbert blight (EFB) is a devastating fungal disease of European hazelnut, Corylus avellana L., and is considered to be the primary reason hazelnuts have not been developed as a commercial crop in the eastern United States. The pathogen, Anisogramma anomala, is native to a wide area east of the Rocky Mountains, where it...

Correlation of electronic monitoring and stylet pathways elucidate the role of sclerenchymatous ring as a barrier to phloem feeding on citrus leaves by Asian citrus psyllid

USDA-ARS?s Scientific Manuscript database

Asian citrus psyllid (ACP, Diaphorina. citri) feeding behaviors play a significant role in the transmission of the phloem-limited Candidatus Liberibacter asiaticus (CLas) bacterium that causes the economically devastating citrus greening disease. Recent studies have shown a fibrous ring of thick-wal...

De novo assembly and phasing of dikaryotic genomes from two isolates of Puccini coronata f. sp. avenae, the causal agent of oat crown rust

Treesearch

Marisa E. Miller; Ying Zhang; Vahid Omidvar; Jana Sperschneider; Benjamin Schwessinger; Castle Raley; Jonathan M. Palmer; Diana Garnica; Narayana Upadhyaya; John Rathjen; Jennifer M. Taylor; Robert F. Park; Peter N. Dodds; Cory D. Hirsch; Shahryar F. Kianian; Melania Figueroa

2018-01-01

Oat crown rust, caused by the fungus Pucinnia coronata f. sp. avenae, is a devastating disease that impacts worldwide oat production. For much of its life cycle, P. coronata f. sp. avenae is dikaryotic, with two separate haploid nuclei that may vary in virulence genotype, highlighting...

Use of multiple sequencing technologies to produce a high-quality genome of the fungus Pseudogymnoascus destructans, the causative agent of bat white-nose syndrome

Treesearch

Kevin P. Drees; Jonathan M. Palmer; Robert Sebra; Jeffrey M. Lorch; Cynthia Chen; Cheng-Cang Wu; Jin Woo Bok; Nancy P. Keller; David S. Blehert; Christina A. Cuomo; Daniel L. Lindner; Jeffrey T. Foster

2016-01-01

White-nose syndrome has recently emerged as one of the most devastating wildlife diseases recorded, causing widespread mortality in numerous bat species throughout eastern North America. Here, we present an improved reference genome of the fungal pathogen Pseudogymnoascus destructans for use in comparative genomic studies.

Unraveling the Mysteries of Progeria | Center for Cancer Research

Cancer.gov

Hutchinson-Gilford progeria syndrome is a rare and devastating genetic disorder in which patients appear normal at birth, but by 12 to 18 months display signs of premature aging such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Because no treatments currently exist, most patients with progeria die in their mid-teens from heart

Stem rust resistance in 1BL.1RS and 2RL.2BS double wheat-rye translocation lines

USDA-ARS?s Scientific Manuscript database

The wheat stem rust pathogen, Puccinia graminis f. sp. tritici, is a significant and devastating disease of wheat crops worldwide. Wheat has many wild relatives in which to source new resistance genes, including the cereal crop of rye in the tertiary genepool. The aim of this study was to assess the...

Teaching Conflict Management Skills in Schools: Prerequisite for Peace and Achievement of Millennium Development Goals in Kenya

ERIC Educational Resources Information Center

Dawo, Jane Irene A.; Wagah, Mical Ongachi

2011-01-01

The Kenyan society is experiencing a lot of conflicts, some with devastating effects such as deaths, starvation, disease and destruction. These normally arise out of difference between people. Secondary schools being part of the society have not been left out of this challenge as evidenced by mass media reports on strikes, demonstrations and…

Animal Models to Study Gluten Sensitivity1

PubMed Central

Marietta, Eric V.; Murray, Joseph A.

2012-01-01

The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70–80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease. PMID:22572887

Effect of Economic Assets on Sexual Risk-Taking Intentions Among Orphaned Adolescents in Uganda

PubMed Central

Han, Chang-Keun; Neilands, Torsten B.; Ismayilova, Leyla; Sperber, Elizabeth

2010-01-01

Objectives. We examined the effect of economic assets on sexual risk-taking intentions among school-going AIDS-orphaned adolescents in rural Uganda. Methods. AIDS-orphaned adolescents from 15 comparable schools were randomly assigned to control (n = 133) or treatment (n = 127) conditions. Treatment participants received child savings accounts, workshops, and mentorship. This economic intervention was in addition to the traditional care and support services for school-going orphaned adolescents (counseling and school supplies) provided to both treatment and control groups. Adolescents in the treatment condition were compared with adolescents in the control condition at baseline and at 10 months after the intervention. Results. After control for sociodemographic factors, child-caregiver/parental communication, and peer pressure, adolescents in the economic intervention group reported a significant reduction in sexual risk-taking intentions compared with adolescents in the control condition. Conclusions. The findings indicate that in Uganda, a country devastated by poverty and disease (including HIV/AIDS), having access to economic assets plays an important role in influencing adolescents' sexual risk-taking intentions. These findings have implications for the care and support of orphaned adolescents, especially in poor African countries devastated by poverty and sexually transmitted diseases. PMID:20075323

Nucleic-acid testing, new platforms and nanotechnology for point-of-decision diagnosis of animal pathogens.

PubMed

Teles, Fernando; Fonseca, Luís

2015-01-01

Accurate disease diagnosis in animals is crucial for animal well-being but also for preventing zoonosis transmission to humans. In particular, livestock diseases may constitute severe threats to humans due to the particularly high physical contact and exposure and, also, be the cause of important economic losses, even in non-endemic countries, where they often arise in the form of rapid and devastating epidemics. Rapid diagnostic tests have been used for a long time in field situations, particularly during outbreaks. However, they mostly rely on serological approaches, which may confirm the exposure to a particular pathogen but may be inappropriate for point-of-decision (point-of-care) settings when emergency responses supported on early and accurate diagnosis are required. Moreover, they often exhibit modest sensitivity and hence significantly depend on later result confirmation in central or reference laboratories. The impressive advances observed in recent years in materials sciences and in nanotechnology, as well as in nucleic-acid synthesis and engineering, have led to an outburst of new in-the-bench and prototype tests for nucleic-acid testing towards point-of-care diagnosis of genetic and infectious diseases. Manufacturing, commercial, regulatory, and technical nature issues for field applicability more likely have hindered their wider entrance into veterinary medicine and practice than have fundamental science gaps. This chapter begins by outlining the current situation, requirements, difficulties, and perspectives of point-of-care tests for diagnosing diseases of veterinary interest. Nucleic-acid testing, particularly for the point of care, is addressed subsequently. A range of valuable signal transduction mechanisms commonly employed in proof-of-concept schemes and techniques born on the analytical chemistry laboratories are also described. As the essential core of this chapter, sections dedicated to the principles and applications of microfluidics, lab-on-a-chip, and nanotechnology for the development of point-of-care tests are presented. Microdevices already applied or under development for application in field diagnosis of animal diseases are reviewed.

Examining Object Location and Object Recognition Memory in Mice

PubMed Central

Vogel-Ciernia, Annie; Wood, Marcelo A.

2014-01-01

Unit Introduction The ability to store and recall our life experiences defines a person's identity. Consequently, the loss of long-term memory is a particularly devastating part of a variety of cognitive disorders, diseases and injuries. There is a great need to develop therapeutics to treat memory disorders, and thus a variety of animal models and memory paradigms have been developed. Mouse models have been widely used both to study basic disease mechanisms and to evaluate potential drug targets for therapeutic development. The relative ease of genetic manipulation of Mus musculus has led to a wide variety of genetically altered mice that model cognitive disorders ranging from Alzheimer's disease to autism. Rodents, including mice, are particularly adept at encoding and remembering spatial relationships, and these long-term spatial memories are dependent on the medial temporal lobe of the brain. These brain regions are also some of the first and most heavily impacted in disorders of human memory including Alzheimer's disease. Consequently, some of the simplest and most commonly used tests of long-term memory in mice are those that examine memory for objects and spatial relationships. However, many of these tasks, such as Morris water maze and contextual fear conditioning, are dependent upon the encoding and retrieval of emotionally aversive and inherently stressful training events. While these types of memories are important, they do not reflect the typical day-to-day experiences or memories most commonly affected in human disease. In addition, stress hormone release alone can modulate memory and thus obscure or artificially enhance these types of tasks. To avoid these sorts of confounds, we and many others have utilized tasks testing animals’ memory for object location and novel object recognition. These tasks involve exploiting rodents’ innate preference for novelty, and are inherently not stressful. In this protocol we detail how memory for object location and object identity can be used to evaluate a wide variety of mouse models and treatments. PMID:25297693

A perspective on targeting non-structural proteins to combat neglected tropical diseases: Dengue, West Nile and Chikungunya viruses.

PubMed

Bhakat, Soumendranath; Karubiu, Wilson; Jayaprakash, Venkatesan; Soliman, Mahmoud E S

2014-11-24

Neglected tropical diseases are major causes of fatality in poverty stricken regions across Africa, Asia and some part of America. The combined potential health risk associated with arthropod-borne viruses (arboviruses); Dengue virus (DENV), West Nile Virus (WNV) and Chikungunya Virus (CHIKV) is immense. These arboviruses are either emerging or re-emerging in many regions with recent documented outbreaks in the United States. Despite several recent evidences of emergence, currently there are no approved drugs or vaccines available to counter these diseases. Non-structural proteins encoded by these RNA viruses are essential for their replication and maturation and thus may offer ideal targets for developing antiviral drugs. In recent years, several protease inhibitors have been sourced from plant extract, synthesis, computer aided drug design and high throughput screening as well as through drug reposition based approaches to target the non-structural proteins. The protease inhibitors have shown different levels of inhibition and may thus provide template to develop selective and potent drugs against these devastating arboviruses. This review seeks to shed light on the design and development of antiviral drugs against DENV, WNV and CHIKV to date. To the best of our knowledge, this review provides the first comprehensive update on the development of protease inhibitors targeting non-structural proteins of three most devastating arboviruses, DENV, WNV and CHIKV. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Impulsive and Compulsive Behaviours in Parkinson's disease

PubMed Central

Averbeck, BB; O’Sullivan, SS; Djamshidian, A

2014-01-01

Impulsive compulsive behaviours (ICBs) in Parkinson’s disease (PD) are a common and devastating side effect of dopamine replacement therapy. In this review we describe the phenomenology, prevalence and risk factors of these patients. Results of behavioural studies assessing the neuropsychological profile emphasize that the ICBs, which are behavioural addictions, are not hedonically motivated. Rather, other factors such as the inability to cope with uncertainty may be triggering ICBs. New insights from functional imaging studies, strengthening the incentive salience hypothesis are discussed and therapeutic guidelines for the management of ICBs in PD are given. PMID:24313567

Satellite techniques yield insight into devastating rainfall from Hurricane Mitch

NASA Astrophysics Data System (ADS)

Ferraro, R.; Vicente, G.; Ba, M.; Gruber, A.; Scofield, R.; Li, Q.; Weldon, R.

Hurricane Mitch may prove to be one of the most devastating tropical cyclones to affect the western hemisphere. Heavy rains over Central America from October 28, 1998, to November 1, 1998, caused widespread flooding and mud slides in Nicaragua and Honduras resulting in thousands of deaths and missing persons. News reports indicated entire towns being swept away, destruction of national economies and infrastructure, and widespread disease in the aftermath of the storm, which some estimates suggested dropped as much as 1300 mm of rain.However, in view of the widespread damage it is difficult to determine the actual amounts and distribution of rainfall. More accurate means of determining the rainfall associated with Mitch are vital for diagnosing and understanding the evolution of this disaster and for developing new mitigation strategies for future tropical cyclones. Satellite data may prove to be a reliable resource for accurate rainfall analysis and have yielded apparently reliable figures for Hurricane Mitch.

Cytokines in the central nervous system: regulatory roles in neuronal function, cell death and repair.

PubMed

Sei, Y; Vitković, L; Yokoyama, M M

1995-01-01

Recent evidence suggests that neurons and glia can synthesize and secrete cytokines, which play critical roles in maintaining homeostasis in the central nervous system (CNS) by mediating the interaction between cells via autocrine or paracrine mechanisms. Circulating cytokines and soluble receptors also regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction and/or cell death and contribute to the pathogenesis of the CNS diseases (e.g., ischemia, Alzheimer's disease and HIV encephalopathy). Defining the molecular pathways of cytokine dysregulation and neurotoxicity may help to elucidate potential therapeutic interventions for many devastating CNS diseases.

Small Ruminant Lentiviruses (SRLVs) Break the Species Barrier to Acquire New Host Range

PubMed Central

Minardi da Cruz, Juliano Cezar; Singh, Dinesh Kumar; Lamara, Ali; Chebloune, Yahia

2013-01-01

Zoonotic events of simian immunodeficiency virus (SIV) from non-human primates to humans have generated the acquired immunodeficiency syndrome (AIDS), one of the most devastating infectious disease of the last century with more than 30 million people dead and about 40.3 million people currently infected worldwide. Human immunodeficiency virus (HIV-1 and HIV-2), the two major viruses that cause AIDS in humans are retroviruses of the lentivirus genus. The genus includes arthritis-encephalitis virus (CAEV) and Maedi-Visna virus (MVV), and a heterogeneous group of viruses known as small ruminant lentiviruses (SRLVs), affecting goat and sheep. Lentivirus genome integrates into the host DNA, causing persistent infection associated with a remarkable diversity during viral replication. Direct evidence of mixed infections with these two closely related SRLVs was found in both sheep and goats. The evidence of a genetic continuum with caprine and ovine field isolates demonstrates the absence of an efficient species barrier preventing cross-species transmission. In dual-infected animals, persistent infections with both CAEV and MVV have been described, and viral chimeras have been detected. This not only complicates animal trade between countries but favors the risk that highly pathogenic variants may emerge as has already been observed in the past in Iceland and, more recently, in outbreaks with virulent strains in Spain. SRLVs affecting wildlife have already been identified, demonstrating the existence of emergent viruses adapted to new hosts. Viruses adapted to wildlife ruminants may acquire novel biopathological properties which may endanger not only the new host species but also domestic ruminants and humans. SRLVs infecting sheep and goats follow a genomic evolution similar to that observed in HIV or in other lentiviruses. Lentivirus genetic diversity and host factors leading to the establishment of naturally occurring virulent versus avirulent infections, in addition to the emergence of new strains, challenge every aspect of SRLV control measures for providing efficient tools to prevent the transmission of diseases between wild ungulates and livestock. PMID:23881276

Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

PubMed Central

Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

2015-01-01

Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

[Ebola and Marburg hemorrhagic fever viruses: update on filoviruses].

PubMed

Leroy, E; Baize, S; Gonzalez, J P

2011-04-01

The Ebola and Marburg viruses are the sole members of the Filoviridae family of viruses. They are characterized by a long filamentous form that is unique in the viral world. Filoviruses are among the most virulent pathogens currently known to infect humans. They cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. Epidemic outbreaks of Marburg and Ebola viruses have taken a heavy toll on human life in Central Africa and devastated large ape populations in Gabon and Republic of Congo. Since their discovery in 1967 (Marburg) and 1976 (Ebola), more than 2,300 cases and 1,670 deaths have been reported. These numbers pale in comparison with the burden caused by malnutrition or other infectious disease scourges in Africa such as malaria, cholera, AIDS, dengue or tuberculosis. However, due to their extremely high lethality, association with multifocal hemorrhaging and specificity to the African continent, these hemorrhagic fever viruses have given rise to great interest on the part not only of the international scientific community but also of the general public because of their perceived potential as biological weapons. Much research has been performed on these viruses and major progress has been made in knowledge of their ecology, epidemiology and physiopathology and in development of vaccine candidates and therapeutic schemes. The purpose of this review is to present the main developments in these particular fields in the last decade.

New Medical and Surgical Insights Into Neonatal Necrotizing Enterocolitis: A Review.

PubMed

Frost, Brandy L; Modi, Biren P; Jaksic, Tom; Caplan, Michael S

2017-01-01

Necrotizing enterocolitis (NEC) has long remained a significant cause of morbidity and mortality in neonatal intensive care units. While the mainstay of treatment for this devastating condition remains largely supportive, research efforts continue to be directed toward understanding pathophysiology as well as how best to approach surgical management when indicated. In this review, we first examine recent medical observations, including overviews on the microbiome and a brief review of the use of probiotics. Next, we discuss the use of biomarkers and how clinicians may be able to use them in the future to predict the course of disease and, perhaps, the need for surgical intervention. We then provide an overview on the use of exclusive human milk feeding and the utility of this approach in preventing NEC. Finally, we discuss recent developments in the surgical management of NEC, beginning with indications for surgery and following with a section on technical surgical considerations, including peritoneal drain vs laparotomy. The review concludes with outcomes from infants with surgically treated NEC. Although medical treatment options for NEC are largely unchanged, understanding of the disease continues to evolve. As new research methods are developed, NEC pathophysiology can be more completely understood. In time, it is hoped that data from ongoing and planned clinical trials will allow us to routinely add targeted preventive measures in addition to human milk, such as prebiotics and probiotics, to the management of high-risk infants. In addition, the discovery of novel biomarkers may not only prove useful in predicting severity of illness but also will hopefully allow for identification of the disease prior to onset of clinical signs. Finally, continued investigation into optimizing surgical outcomes is essential in this population of infants, many of whom require long-term parenteral therapy and intestinal rehabilitation.

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

PubMed

Batista, Andre F; Forny-Germano, Leticia; Clarke, Julia R; Lyra E Silva, Natalia M; Brito-Moreira, Jordano; Boehnke, Susan E; Winterborn, Andrew; Coe, Brian C; Lablans, Ann; Vital, Juliana F; Marques, Suelen A; Martinez, Ana Mb; Gralle, Matthias; Holscher, Christian; Klein, William L; Houzel, Jean-Christophe; Ferreira, Sergio T; Munoz, Douglas P; De Felice, Fernanda G

2018-05-01

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AβOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.