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Sample records for model human fungal

  1. Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

    Science.gov (United States)

    Leach, Michelle D; Tyc, Katarzyna M; Brown, Alistair J P; Klipp, Edda

    2012-01-01

    Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

  2. Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

    Directory of Open Access Journals (Sweden)

    Michelle D Leach

    Full Text Available Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

  3. Immunology of fungal infections: lessons learned from animal models.

    Science.gov (United States)

    Steele, Chad; Wormley, Floyd L

    2012-08-01

    The continuing AIDS epidemic coupled with increased usage of immunosuppressive drugs to prevent organ rejection or treat autoimmune diseases has resulted in an increase in individuals at risk for acquiring fungal diseases. These concerns highlight the need to elucidate mechanisms of inducing protective immune responses against fungal pathogens. Consequently, several experimental models of human mycoses have been developed to study these diseases. The availability of transgenic animal models allows for in-depth analysis of specific components, receptors, and signaling pathways that elicit protection against fungal diseases. This review focuses on recent advances in our understanding of immune responses to fungal infections gained using animal models.

  4. Model simulations of fungal spore distribution over the Indian region

    Science.gov (United States)

    Ansari, Tabish U.; Valsan, Aswathy E.; Ojha, N.; Ravikrishna, R.; Narasimhan, Balaji; Gunthe, Sachin S.

    2015-12-01

    Fungal spores play important role in the health of humans, animals, and plants by constituting a class of the primary biological aerosol particles (PBAPs). Additionally, these could mediate the hydrological cycle by acting as nuclei for ice and cloud formation (IN and CCN respectively). Various processes in the biosphere and the variations in the meteorological conditions control the releasing mechanism of spores through active wet and dry discharge. In the present paper, we simulate the concentration of fungal spores over the Indian region during three distinct meteorological seasons by combining a numerical model (WRF-Chem) with the fungal spore emissions based on land-use type. Maiden high-resolution regional simulations revealed large spatial gradient and strong seasonal dependence in the concentration of fungal spores over the Indian region. The fungal spore concentrations are found to be the highest during winter (0-70 μg m-3 in December), moderately higher during summer (0-35 μg m-3 in May) and lowest during the monsoon (0-25 μg m-3 in July). The elevated concentrations during winter are attributed to the shallower boundary layer trapping the emitted fungal spores in smaller volume. In contrast, the deeper boundary layer mixing in May and stronger monsoonal-convection in July distribute the fungal spores throughout the lower troposphere (∼5 km). We suggest that the higher fungal spore concentrations during winter could have potential health impacts. While, stronger vertical mixing could enable fungal spores to influence the cloud formation during summer and monsoon. Our study provides the first information about the distribution and seasonal variation of fungal spores over the densely populated and observationally sparse Indian region.

  5. Sexual reproduction of human fungal pathogens.

    Science.gov (United States)

    Heitman, Joseph; Carter, Dee A; Dyer, Paul S; Soll, David R

    2014-08-01

    We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms.

  6. Modelling Fungal Fermentations for Enzyme Production

    DEFF Research Database (Denmark)

    Albæk, Mads Orla; Gernaey, Krist; Hansen, Morten S.

    We have developed a process model of fungal fed-batch fermentations for enzyme production. In these processes, oxygen transfer rate is limiting and controls the substrate feeding rate. The model has been shown to describe cultivations of both Aspergillus oryzae and Trichoderma reesei strains in 550...

  7. Modelling combat strategies in fungal mycelia.

    Science.gov (United States)

    Boswell, Graeme P

    2012-07-07

    Fungal mycelia have a well-established role in nutrient cycling and are widely used as agents in biological control and in the remediation of polluted landscapes. Competition and combat between different fungal communities is common in these contexts and its outcome impacts on local biodiversity and the success of such biotechnological applications. In this investigation a mathematical model representing mycelia as a system of partial differential equations is used to simulate combat between two fungal colonies growing into a nutrient-free domain. The resultant equations are integrated numerically and the model simulates well-established outcomes of combat between fungal communities. The outcome of pairwise combat is shown to depend on numerous factors including the suppression of advancing hyphae in rivals, the degradation of a rival's established biomass and the utilization and redistribution of available nutrient resources. It is demonstrated how non-transitive hierarchies in fungal communities can be established through switching mechanisms, mirroring observations reported in experimental studies, and how specialized defensive structures can emerge through changes in the redistribution of internal resources.

  8. First genomic survey of human skin fungal diversity

    Science.gov (United States)

    Fungal infections of the skin affect 29 million people in the United States. In the first study of human fungal skin diversity, National Institutes of Health researchers sequenced the DNA of fungi that thrive at different skin sites of healthy adults to d

  9. Molecular Identification of Human Fungal Pathogens

    Science.gov (United States)

    2011-03-01

    no pigment seen on the hyphal walls on hematoxylin-eosin or melan A staining. The biopsy specimen was sent for bacterial and fungal cul- tures, but the...aim was to design universal primers and then develop a PCR mix, which would be able to reliably amplify template from any specimen, even pigmented ...which if accepted, will result in thirty journal publications. There was also one book chapter published. II. Seventeen abstracts have been

  10. Human Dectin-1 Deficiency and Mucocutaneous Fungal Infections

    Science.gov (United States)

    Ferwerda, Bart; Ferwerda, Gerben; Plantinga, Theo S.; Willment, Janet A.; van Spriel, Annemiek B.; Venselaar, Hanka; Elbers, Clara C.; Johnson, Melissa D.; Cambi, Alessandra; Huysamen, Cristal; Jacobs, Liesbeth; Jansen, Trees; Verheijen, Karlijn; Masthoff, Laury; Morré, Servaas A.; Vriend, Gert; Williams, David L.; Perfect, John R.; Joosten, Leo A.B.; Wijmenga, Cisca; van der Meer, Jos W.M.; Adema, Gosse J.; Kullberg, Bart Jan; Brown, Gordon D.; Netea, Mihai G.

    2009-01-01

    SUMMARY Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the β-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate β-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with β-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense. PMID:19864674

  11. Modulation of Human Immune Response by Fungal Biocontrol Agents

    Science.gov (United States)

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A.; Vannier-Santos, Marcos A.; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses. PMID:28217107

  12. An evolutionary perspective on zinc uptake by human fungal pathogens†

    Science.gov (United States)

    Wilson, Duncan

    2015-01-01

    The mammalian immune system has evolved sophisticated mechanisms to withhold essential micronutrients from invading pathogens. These processes, collectively known as nutritional immunity serve to limit microbial proliferation and bolster killing of the invader. Successful pathogens, therefore, have developed strategies to counteract nutritional immunity and acquire essential micronutrients in the restrictive environment of the infected host. Here I take advantage of the now large number of sequenced fungal genomes to explore the zinc acquisition strategies of human fungal pathogens and reflect on the evolutionary context of these uptake pathways. PMID:25652414

  13. The burden of serious human fungal infections in Brazil.

    Science.gov (United States)

    Giacomazzi, Juliana; Baethgen, Ludmila; Carneiro, Lilian C; Millington, Maria Adelaide; Denning, David W; Colombo, Arnaldo L; Pasqualotto, Alessandro C

    2016-03-01

    In Brazil, human fungal infections are prevalent, however, these conditions are not officially reportable diseases. To estimate the burden of serious fungal diseases in 1 year in Brazil, based on available data and published literature. Historical official data from fungal diseases were collected from Brazilian Unified Health System Informatics Department (DATASUS). For fungal diseases for which no official data were available, assumptions of frequencies were made by estimating based on published literature. The incidence (/1000) of hospital admissions for coccidioidomycosis was 7.12; for histoplasmosis, 2.19; and for paracoccidioidomycosis, 7.99. The estimated number of cryptococcal meningoencephalitis cases was 6832. Also, there were 4115 cases of Pneumocystis pneumonia in AIDS patients per year, 1 010 465 aspergillosis and 2 981 416 cases of serious Candida infections, including invasive and non-invasive diseases. In this study, we demonstrate that more than 3.8 million individuals in Brazil may be suffering from serious fungal infections, mostly patients with malignant cancers, transplant recipients, asthma, previous tuberculosis, HIV infection and those living in endemic areas for truly pathogenic fungi. The scientific community and the governmental agencies should work in close collaboration in order to reduce the burden of such complex, difficult-to-diagnose and hard to treat diseases.

  14. A novel model of invasive fungal rhinosinusitis in rats.

    Science.gov (United States)

    Zhang, Fang; An, Yunfang; Li, Zeqing; Zhao, Changqing

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a life-threatening inflammatory disease that affects immunocompromised patients, but animal models of the disease are scarce. This study aimed to develop an IFRS model in neutropenic rats. The model was established in three consecutive steps: unilateral nasal obstruction with Merocel sponges, followed by administration of cyclophosphamide (CPA), and, finally, nasal inoculation with Aspergillus fumigatus. Fifty healthy Wistar rats were randomly divided into five groups, with group I as the controls, group II undergoing unilateral nasal obstruction alone, group III undergoing nasal obstruction with fungal inoculation, group IV undergoing nasal obstruction with administration of CPA, and group V undergoing nasal obstruction with administration of CPA and fungal inoculation. Hematology, histology, and mycology investigations were performed. The changes in the rat absolute neutrophil counts (ANCs) were statistically different across the groups. The administration of CPA decreased the ANCs, whereas nasal obstruction with fungal inoculation increased the ANCs, and nasal obstruction did not change them. Histological examination of the rats in group V revealed the hyphal invasion of sinus mucosa and bone, thrombosis, and tissue infarction. No pathology indicative of IFRS was observed in the remaining groups. Positive rates of fungal culture in tissue homogenates from the maxillary sinus (62.5%) and lung (25%) were found in group V, whereas groups I, II, III, and IV showed no fungal culture in the homogenates. A rat IFRS model was successfully developed through nasal obstruction, CPA-induced neutropenia, and fungal inoculation. The disease model closely mimics the pathophysiology of anthropic IFRS.

  15. Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

    OpenAIRE

    Desjardins, Christopher A; Champion, Mia D.; Holder, Jason W.; Muszewska, Anna; Goldberg, Jonathan; Bailao, Alexandre M.; Brigido, Marcelo de Macedo; Silva Ferreira, Marcia Eliana da; Garcia, Ana Maria; Grynberg, Marcin; Gujja, Sharvari; Heiman, David I.; Henn, Matthew R.; Kodira, Chinnappa D.; Leon-Narvaez, Henry

    2011-01-01

    Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasi...

  16. Discovery of a novel dual fungal CYP51/human 5-lipoxygenase inhibitor: implications for anti-fungal therapy.

    Directory of Open Access Journals (Sweden)

    Eric K Hoobler

    Full Text Available We report the discovery of a novel dual inhibitor targeting fungal sterol 14α-demethylase (CYP51 or Erg11 and human 5-lipoxygenase (5-LOX with improved potency against 5-LOX due to its reduction of the iron center by its phenylenediamine core. A series of potent 5-LOX inhibitors containing a phenylenediamine core, were synthesized that exhibit nanomolar potency and >30-fold selectivity against the LOX paralogs, platelet-type 12-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity against ovine cyclooxygenase-1 and human cyclooxygnease-2. The phenylenediamine core was then translated into the structure of ketoconazole, a highly effective anti-fungal medication for seborrheic dermatitis, to generate a novel compound, ketaminazole. Ketaminazole was found to be a potent dual inhibitor against human 5-LOX (IC50 = 700 nM and CYP51 (IC50 = 43 nM in vitro. It was tested in whole blood and found to down-regulate LTB4 synthesis, displaying 45% inhibition at 10 µM. In addition, ketaminazole selectively inhibited yeast CYP51 relative to human CYP51 by 17-fold, which is greater selectivity than that of ketoconazole and could confer a therapeutic advantage. This novel dual anti-fungal/anti-inflammatory inhibitor could potentially have therapeutic uses against fungal infections that have an anti-inflammatory component.

  17. Fungal diseases: an emerging threat to human, animal, and plant health : workshop summary

    National Research Council Canada - National Science Library

    Olsen, LeighAnne

    2011-01-01

    "Fungal diseases have contributed to death and disability in humans, triggered global wildlife extinctions and population declines, devastated agricultural crops, and altered forest ecosystem dynamics...

  18. Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

    Directory of Open Access Journals (Sweden)

    Alessandra da Silva Dantas

    2015-02-01

    Full Text Available Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS, such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen.

  19. Plant production of anti-β-glucan antibodies for immunotherapy of fungal infections in humans.

    Science.gov (United States)

    Capodicasa, Cristina; Chiani, Paola; Bromuro, Carla; De Bernardis, Flavia; Catellani, Marcello; Palma, Angelina S; Liu, Yan; Feizi, Ten; Cassone, Antonio; Benvenuto, Eugenio; Torosantucci, Antonella

    2011-09-01

    There is an increasing interest in the development of therapeutic antibodies (Ab) to improve the control of fungal pathogens, but none of these reagents is available for clinical use. We previously described a murine monoclonal antibody (mAb 2G8) targeting β-glucan, a cell wall polysaccharide common to most pathogenic fungi, which conferred significant protection against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans in animal models. Transfer of this wide-spectrum, antifungal mAb into the clinical setting would allow the control of most frequent fungal infections in many different categories of patients. To this aim, two chimeric mouse-human Ab derivatives from mAb 2G8, in the format of complete IgG or scFv-Fc, were generated, transiently expressed in Nicotiana benthamiana plants and purified from leaves with high yields (approximately 50 mg Ab/kg of plant tissues). Both recombinant Abs fully retained the β-glucan-binding specificity and the antifungal activities of the cognate murine mAb against C. albicans. In fact, they recognized preferentially β1,3-linked glucan molecules present at the fungal cell surface and directly inhibited the growth of C. albicans and its adhesion to human epithelial cells in vitro. In addition, both the IgG and the scFv-Fc promoted C. albicans killing by isolated, human polymorphonuclear neutrophils in ex vivo assays and conferred significant antifungal protection in animal models of systemic or vulvovaginal C. albicans infection. These recombinant Abs represent valuable molecules for developing novel, plant-derived immunotherapeutics against candidiasis and, possibly, other fungal diseases.

  20. Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

    Science.gov (United States)

    Desjardins, Christopher A.; Champion, Mia D.; Holder, Jason W.; Muszewska, Anna; Goldberg, Jonathan; Bailão, Alexandre M.; Brigido, Marcelo Macedo; Ferreira, Márcia Eliana da Silva; Garcia, Ana Maria; Grynberg, Marcin; Gujja, Sharvari; Heiman, David I.; Henn, Matthew R.; Kodira, Chinnappa D.; León-Narváez, Henry; Longo, Larissa V. G.; Ma, Li-Jun; Malavazi, Iran; Matsuo, Alisson L.; Morais, Flavia V.; Pereira, Maristela; Rodríguez-Brito, Sabrina; Sakthikumar, Sharadha; Salem-Izacc, Silvia M.; Sykes, Sean M.; Teixeira, Marcus Melo; Vallejo, Milene C.; Walter, Maria Emília Machado Telles; Yandava, Chandri; Young, Sarah; Zeng, Qiandong; Zucker, Jeremy; Felipe, Maria Sueli; Goldman, Gustavo H.; Haas, Brian J.; McEwen, Juan G.; Nino-Vega, Gustavo; Puccia, Rosana; San-Blas, Gioconda; Soares, Celia Maria de Almeida; Birren, Bruce W.; Cuomo, Christina A.

    2011-01-01

    Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of

  1. Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

    Directory of Open Access Journals (Sweden)

    Christopher A Desjardins

    2011-10-01

    Full Text Available Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18 and one strain of Paracoccidioides lutzii (Pb01. These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic

  2. Evaluation of Human Body Fluids for the Diagnosis of Fungal Infections

    Directory of Open Access Journals (Sweden)

    Parisa Badiee

    2013-01-01

    Full Text Available Invasive fungal infections are a major cause of morbidity and mortality in immunocompromised patients. Because the etiologic agents of these infections are abundant in nature, their isolation from biopsy material or sterile body fluids is needed to document infection. This review evaluates and discusses different human body fluids used to diagnose fungal infections.

  3. Age and gender affect the composition of fungal population of the human gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Francesco Strati

    2016-08-01

    Full Text Available The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C, to acidic and oxidative stress and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics

  4. Host Pathogen Relations: Exploring Animal Models for Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Catherine G. Harwood

    2014-06-01

    Full Text Available Pathogenic fungi cause superficial infections but pose a significant public health risk when infections spread to deeper tissues, such as the lung. Within the last three decades, fungi have been identified as the leading cause of nosocomial infections making them the focus of research. This review outlines the model systems such as the mouse, zebrafish larvae, flies, and nematodes, as well as ex vivo and in vitro systems available to study common fungal pathogens.

  5. Host pathogen relations: exploring animal models for fungal pathogens.

    Science.gov (United States)

    Harwood, Catherine G; Rao, Reeta P

    2014-06-30

    Pathogenic fungi cause superficial infections but pose a significant public health risk when infections spread to deeper tissues, such as the lung. Within the last three decades, fungi have been identified as the leading cause of nosocomial infections making them the focus of research. This review outlines the model systems such as the mouse, zebrafish larvae, flies, and nematodes, as well as ex vivo and in vitro systems available to study common fungal pathogens.

  6. Systemic fungal infections in patients with human inmunodeficiency virus.

    Science.gov (United States)

    Rodríguez-Cerdeira, C; Arenas, R; Moreno-Coutiño, G; Vásquez, E; Fernández, R; Chang, P

    2014-01-01

    Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/μL. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

  7. Mycoviruses : future therapeutic agents of invasive fungal infections in humans?

    NARCIS (Netherlands)

    van de Sande, W. W. J.; Lo-Ten-Foe, J. R.; van Belkum, A.; Netea, M. G.; Kullberg, B. J.; Vonk, A. G.

    Invasive fungal infections are relatively common opportunistic infections in immunocompromised patients and are still associated with a high mortality rate. Furthermore, these infections are often complicated by resistance or refractoriness to current antimicrobial agents. Therefore, an urgent need

  8. Facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions.

    Science.gov (United States)

    Schleicher, Jana; Conrad, Theresia; Gustafsson, Mika; Cedersund, Gunnar; Guthke, Reinhard; Linde, Jörg

    2017-03-01

    Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host-pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. © The Author 2016. Published by Oxford University Press.

  9. Facing the challenges of multiscale modelling of bacterial and fungal pathogen–host interactions

    Science.gov (United States)

    Schleicher, Jana; Conrad, Theresia; Gustafsson, Mika; Cedersund, Gunnar; Guthke, Reinhard

    2017-01-01

    Abstract Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host–pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. PMID:26857943

  10. Adhesins in Human Fungal Pathogens : Glue with Plenty of Stick

    NARCIS (Netherlands)

    de Groot, Piet W. J.; Bader, Oliver; de Boer, Albert D.; Weig, Michael; Chauhan, Neeraj

    2013-01-01

    Understanding the pathogenesis of an infectious disease is critical for developing new methods to prevent infection and diagnose or cure disease. Adherence of microorganisms to host tissue is a prerequisite for tissue invasion and infection. Fungal cell wall adhesins involved in adherence to host ti

  11. The 2012 Fungal Meningitis Outbreak in the United States: Connections Between Soils and Human Health

    Science.gov (United States)

    Burgess, Lynn; Brevik, Eric

    2013-04-01

    In September of 2012 the United States found itself facing a fungal meningitis outbreak that was traced back to contaminated steroid injections. The fungus Exserohilium rostratum, which is found in soil, among other locations in the environment, was identified as the main cause of the health issues created by the contaminated steroids. As of November 7, 2012 419 cases of fungal meningitis, stroke due to presumed fungal meningitis, or other central nervous system-related infections, 10 cases of peripheral joint infections, and 31 deaths linked to the contaminated steroids had been documented. However, the life cycle and soil ecology of E. rostratum is not well understood, and such knowledge would aid human health professionals in understanding the pathogenic potential of E. rostratum. Therefore, soil scientists have a role to play in developing the most effective ways to combat human health challenges such as the 2012 fungal meningitis outbreak.

  12. Aerially transmitted human fungal pathogens: what can we learn from metagenomics and comparative genomics?

    Science.gov (United States)

    Aliouat-Denis, Cécile-Marie; Chabé, Magali; Delhaes, Laurence; Dei-Cas, Eduardo

    2014-01-01

    In the last few decades, aerially transmitted human fungal pathogens have been increasingly recognized to impact the clinical course of chronic pulmonary diseases, such as asthma, cystic fibrosis or chronic obstructive pulmonary disease. Thanks to recent development of culture-free high-throughput sequencing methods, the metagenomic approaches are now appropriate to detect, identify and even quantify prokaryotic or eukaryotic microorganism communities inhabiting human respiratory tract and to access the complexity of even low-burden microbe communities that are likely to play a role in chronic pulmonary diseases. In this review, we explore how metagenomics and comparative genomics studies can alleviate fungal culture bottlenecks, improve our knowledge about fungal biology, lift the veil on cross-talks between host lung and fungal microbiota, and gain insights into the pathogenic impact of these aerially transmitted fungi that affect human beings. We reviewed metagenomic studies and comparative genomic analyses of carefully chosen microorganisms, and confirmed the usefulness of such approaches to better delineate biology and pathogenesis of aerially transmitted human fungal pathogens. Efforts to generate and efficiently analyze the enormous amount of data produced by such novel approaches have to be pursued, and will potentially provide the patients suffering from chronic pulmonary diseases with a better management. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).

  13. The GRF10 homeobox gene regulates filamentous growth in the human fungal pathogen Candida albicans.

    Science.gov (United States)

    Ghosh, Anup K; Wangsanut, Tanaporn; Fonzi, William A; Rolfes, Ronda J

    2015-12-01

    Candida albicans is the most common human fungal pathogen and can cause life-threatening infections. Filamentous growth is critical in the pathogenicity of C. albicans, as the transition from yeast to hyphal forms is linked to virulence and is also a pivotal process in fungal biofilm development. Homeodomain-containing transcription factors have been linked to developmental processes in fungi and other eukaryotes. We report here on GRF10, a homeobox transcription factor-encoding gene that plays a role in C. albicans filamentation. Deletion of the GRF10 gene, in both C. albicans SN152 and BWP17 strain backgrounds, results in mutants with strongly decreased hyphal growth. The mutants are defective in chlamydospore and biofilm formation, as well as showing dramatically attenuated virulence in a mouse infection model. Expression of the GRF10 gene is highly induced during stationary phase and filamentation. In summary, our study emphasizes a new role for the homeodomain-containing transcription factor in morphogenesis and pathogenicity of C. albicans.

  14. Evaluation and a predictive model of airborne fungal concentrations in school classrooms.

    Science.gov (United States)

    Bartlett, Karen H; Kennedy, Susan M; Brauer, Michael; Van Netten, Chris; Dill, Barbara

    2004-08-01

    Exposure to airborne fungal products may be associated with health effects ranging from non-specific irritation of the respiratory tract or mucus membranes to inflammation provoked by specific fungal antigens. While concentrations of airborne fungi are frequently measured in indoor air quality investigations, the significance of these measurements in the absence of visual mold colonization is unclear. This study was undertaken to evaluate concentrations of airborne fungal concentrations in school classrooms within a defined geographic location in British Columbia, Canada, and to build a model to clarify determinants of airborne fungal concentration. All elementary schools within one school district participated in the study. Classrooms examined varied by age, construction and presence or absence of mechanical ventilation. Airborne fungal propagules were collected inside classrooms and outdoors. Variables describing characteristics of the environment, buildings and occupants were measured and used to construct a predictive model of fungal concentration. The classrooms studied were not visibly contaminated by fungal growth. The data were evaluated using available guidelines. However, the published guidelines did not take into account significant aspects of the local environment. For example, there was a statistically significant effect of season on the fungal concentrations and on the proportional representation of fungal genera. Rooms ventilated by mechanical means had significantly lower geometric mean concentrations than naturally ventilated rooms. Environmental (temperature, outdoor fungal concentration), building (age) and ventilation variables accounted for 58% of the variation in the measured fungal concentrations. A methodology is proposed for the evaluation of airborne fungal concentration data which takes into account local environmental conditions as an aid in the evaluation of fungal bioaerosols in public buildings.

  15. Immunomodulatory capacity of fungal proteins on the cytokine production of human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Jeurink, P.V.; Lull Noguera, C.; Savelkoul, H.F.J.; Wichers, H.J.

    2008-01-01

    Immunomodulation by fungal compounds can be determined by the capacity of the compounds to influence the cytokine production by human peripheral blood mononuclear cells (hPBMC). These activities include mitogenicity, stimulation and activation of immune effector cells. Eight mushroom strains (Agaric

  16. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest.

    NARCIS (Netherlands)

    Hagen, F.; Ceresini, P.C.; Polacheck, I.; Ma, H.; Nieuwerburgh, F. van; Gabaldón, T.; Kagan, S.; Pursall, E.R.; Hoogveld, H.L.; Iersel, L.J. van; Klau, G.W.; Kelk, S.M.; Stougie, L.; Bartlett, K.H.; Voelz, K.; Pryszcz, L.P.; Castañeda, E.; Lazera, M.; Meyer, W.; Deforce, D.; Meis, J.F.G.M.; May, R.C.; Klaassen, C.H.; Boekhout, T.

    2013-01-01

    Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause

  17. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest

    NARCIS (Netherlands)

    Hagen, F.; Ceresini, P.C.; Polacheck, I.; Ma, H.; van Nieuwerburgh, F.; Gabaldon, T.; Kagan, S.; Pursall, E.R.; Hoogveld, H.L.; van Iersel, L.J.; Klau, G.W.; Kelk, S.M.; Stougie, L.; Bartlett, K.H.; Voelz, K.; Pryszcz, L.P.; Castaneda, E.; Lazera, M.; Meyer, W.; Deforce, D.; Meis, J.F.G.M.; May, R.C.; Klaassen, C.H.W.; Boekhout, T.

    2013-01-01

    Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause o

  18. Ancient Dispersal of the Human Fungal Pathogen Cryptococcus gattii from the Amazon Rainforest

    NARCIS (Netherlands)

    Hagen, Ferry; Ceresini, Paulo C.; Polacheck, Itzhack; Ma, Hansong; van Nieuwerburgh, Filip; Gabaldon, Toni; Kagan, Sarah; Pursall, E. Rhiannon; Hoogveld, Hans L.; van Iersel, Leo J. J.; Klau, Gunnar W.; Kelk, Steven M.; Stougie, Leen; Bartlett, Karen H.; Voelz, Kerstin; Pryszcz, Leszek P.; Castaneda, Elizabeth; Lazera, Marcia; Meyer, Wieland; Deforce, Dieter; Meis, Jacques F.; May, Robin C.; Klaassen, Corne H. W.; Boekhout, Teun

    2013-01-01

    Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause o

  19. Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

    Directory of Open Access Journals (Sweden)

    Dominik Schreiber

    2017-08-01

    Full Text Available Inflammatory bowel diseases (IBD, which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml, TNF-α (10 ng/ml, and IL-1β (5 ng/ml. Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.

  20. Opportunistic fungi in lake water and fungal infections in associated human population in Dal Lake, Kashmir.

    Science.gov (United States)

    Bandh, Suhaib A; Kamili, Azra N; Ganai, Bashir A; Lone, Bashir A

    2016-04-01

    Natural habitats of opportunistic fungal pathogens are outside of the host; therefore, it is critically important to understand their ecology and routes of transmission. In this study, we investigated the presence of human pathogenic opportunistic fungi in lake water and incidence of fungal infections in associated population in Kashmir, India. Six hundred forty water samples were taken on seasonal basis from a wide network of sampling stations of the lake for an extended period of two years for screening their occurrence. The samples were inoculated onto rose bengal agar, malt extract agar, potato dextrose agar and other specified culture media supplemented with Chloramphenicol and Streptomycin followed by incubation at 37 °C. All the samples were positive for fungi, which were later identified by sequencing the rDNA internal transcribed spacer region aided by classical morphological culture techniques and physiological profiling. The whole process led to the isolation of sixteen species of opportunistic fungal pathogens belonging to genus Aspergillus, Candida, Penicillium, Cryptococcus, Fusarium, Rhizopus and Mucor in decreasing order of prevalence. Furthermore, 20% population (n = 384) of Dal inhabitants was examined for possible fungal infections and it was observed that only 8.07% individuals were positive for fungal infections with 4.68% skin infection cases, 2.34% onychomycosis cases and 1.04% candidiasis cases. Scrapings from onychomycosis and candidiasis patients showed the presence of Aversicolor and Calbicans respectively, resembling exactly the strains isolated from the lake water. However, the skin infection was because of a dermatophyte not isolated for the lake water. Higher prevalence of infection (6.77%) was seen in people using lake water followed by a positive prevalence of 1.30% using tap water. The results of present study suggest that the lake inhabitants are at a greater risk of getting life threatening fungal diseases which may lead to

  1. Comparative genomics allowed the identification of drug targets against human fungal pathogens

    Directory of Open Access Journals (Sweden)

    Martins Natalia F

    2011-01-01

    Full Text Available Abstract Background The prevalence of invasive fungal infections (IFIs has increased steadily worldwide in the last few decades. Particularly, there has been a global rise in the number of infections among immunosuppressed people. These patients present severe clinical forms of the infections, which are commonly fatal, and they are more susceptible to opportunistic fungal infections than non-immunocompromised people. IFIs have historically been associated with high morbidity and mortality, partly because of the limitations of available antifungal therapies, including side effects, toxicities, drug interactions and antifungal resistance. Thus, the search for alternative therapies and/or the development of more specific drugs is a challenge that needs to be met. Genomics has created new ways of examining genes, which open new strategies for drug development and control of human diseases. Results In silico analyses and manual mining selected initially 57 potential drug targets, based on 55 genes experimentally confirmed as essential for Candida albicans or Aspergillus fumigatus and other 2 genes (kre2 and erg6 relevant for fungal survival within the host. Orthologs for those 57 potential targets were also identified in eight human fungal pathogens (C. albicans, A. fumigatus, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Paracoccidioides lutzii, Coccidioides immitis, Cryptococcus neoformans and Histoplasma capsulatum. Of those, 10 genes were present in all pathogenic fungi analyzed and absent in the human genome. We focused on four candidates: trr1 that encodes for thioredoxin reductase, rim8 that encodes for a protein involved in the proteolytic activation of a transcriptional factor in response to alkaline pH, kre2 that encodes for α-1,2-mannosyltransferase and erg6 that encodes for Δ(24-sterol C-methyltransferase. Conclusions Our data show that the comparative genomics analysis of eight fungal pathogens enabled the identification of

  2. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide

    OpenAIRE

    2010-01-01

    Specific regulatory nascent chains establish direct interactions with the ribosomal tunnel, leading to translational stalling. Despite a wealth of biochemical data, structural insight into the mechanism of translational stalling in eukaryotes is still lacking. Here we use cryo-electron microscopy to visualize eukaryotic ribosomes stalled during the translation of two diverse regulatory peptides: the fungal arginine attenuator peptide (AAP) and the human cytomegalovirus (hCMV) gp48 upstream op...

  3. Fungal rhinosinusitis.

    Science.gov (United States)

    Netkovski, J; Shirgoska, B

    2012-01-01

    Fungi are a major part of the ecosystem. In fact, over 250 fungal species have been reported to produce human infections. More than ever, fungal diseases have emerged as major challenges for physicians and clinical microbiologists. The aim of this study was to summarize the diagnostic procedures and endoscopic surgical treatment of patients with fungal rhinosinusitis. Eleven patients, i.e. 10% of all cases with chronic inflammation of paranasal sinuses, were diagnosed with fungal rhinosinusitis. Ten of them were patients with a noninvasive form, fungus ball, while only one patient was classified in the group of chronic invasive fungal rhinosinusitis which was accompanied with diabetes mellitus. All patients underwent nasal endoscopic examination, skin allergy test and had preoperative computed tomography (CT) scans of the sinuses in axial and coronal plane. Functional endoscopic sinus surgery was performed in 10 patients with fungus ball, while a combined approach, endoscopic and external, was done in the immunocompromised patient with the chronic invasive form of fungal rhinosinusitis. Most cases (9/11) had unilateral infection. In 9 cases infection was restricted to a single sinus, and here the maxillary sinus was most commonly affected (8/9) with infections in other patients being restricted to the sphenoid sinus (1/9). Two patients had infections affecting two or more sinuses. In patients with an invasive form of the fungal disease there was involvement of the periorbital and orbital tissues. In patients with fungus ball the mycelia masses were completely removed from the sinus cavities. Long-term outcome was positive in all the operated patients and no recurrence was detected. The most frequent fungal agent that caused rhinosinusitis was Aspergillus. Mucor was identified in the patient with the invasive form. Endoscopic examination of the nasal cavity and CT scanning of paranasal sinuses followed by endoscopic sinus surgery were represented as valuable

  4. Estimated Burden of Serious Fungal Infections in Jamaica by Literature Review and Modelling

    Science.gov (United States)

    Gugnani, HC; Denning, DW

    2015-01-01

    ABSTRACT Objective: Jamaica is one of the largest countries in the Caribbean with a population of 2 706 500. Prevalence of human immunodeficiency virus (HIV) in Jamaica is high, while that of tuberculosis (TB) is recorded to be low. In this study, we have estimated the burden of serious fungal infections and some other mycoses in Jamaica. Methods: All published papers reporting on rates of fungal infections in Jamaica and the Caribbean were identified through extensive search of the literature. We also extracted data from published papers on epidemiology and from the World Health Organization (WHO) TB Programme and UNAIDS. Chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) rates were derived from asthma and TB rates. Where there were no available data on some mycoses, we used specific populations at risk and frequencies of fungal infection of each to estimate national prevalence. Results: Over 57 600 people in Jamaica probably suffer from serious fungal infections each year, most related to ‘fungal asthma’ (ABPA and SAFS), recurrent vulvovaginal candidiasis and AIDS-related opportunistic infections. Histoplasmosis is endemic in Jamaica, though only a few clinical cases are known. Pneumocystis pneumonia is frequent while cryptococcosis and aspergillosis are rarely recorded. Tinea capitis was common in children. Recurrent vulvovaginal candidiasis is very common (3154/100 000) and candidaemia occurs. Subcutaneous mycoses such as chromoblastomycosis and mycetoma also seem to be relatively common. Conclusion: Local epidemiological studies are urgently required to validate or modify these estimates of serious fungal infections in Jamaica. PMID:26426178

  5. A fungal growth model fitted to carbon-limited dynamics of Rhizoctonia solani

    NARCIS (Netherlands)

    Jeger, M.J.; Lamour, A.; Gilligan, C.A.; Otten, W.

    2008-01-01

    Here, a quasi-steady-state approximation was used to simplify a mathematical model for fungal growth in carbon-limiting systems, and this was fitted to growth dynamics of the soil-borne plant pathogen and saprotroph Rhizoctonia solani. The model identified a criterion for invasion into

  6. CD103+ Conventional Dendritic Cells Are Critical for TLR7/9-Dependent Host Defense against Histoplasma capsulatum, an Endemic Fungal Pathogen of Humans.

    Directory of Open Access Journals (Sweden)

    Nancy Van Prooyen

    2016-07-01

    Full Text Available Innate immune cells shape the host response to microbial pathogens. Here we elucidate critical differences in the molecular response of macrophages vs. dendritic cells (DCs to Histoplasma capsulatum, an intracellular fungal pathogen of humans. It has long been known that macrophages are permissive for Histoplasma growth and succumb to infection, whereas DCs restrict fungal growth and survive infection. We used murine macrophages and DCs to identify host pathways that influence fungal proliferation and host-cell viability. Transcriptional profiling experiments revealed that DCs produced a strong Type I interferon (IFN-I response to infection with Histoplasma yeasts. Toll-like receptors 7 and 9 (TLR7/9, which recognize nucleic acids, were required for IFN-I production and restriction of fungal growth in DCs, but mutation of TLR7/9 had no effect on the outcome of macrophage infection. Moreover, TLR7/9 were essential for the ability of infected DCs to elicit production of the critical cytokine IFNγ from primed CD4+ T cells in vitro, indicating the role of this pathway in T cell activation. In a mouse model of infection, TLR7/9 were required for optimal production of IFN-I and IFNγ, host survival, and restriction of cerebral fungal burden. These data demonstrate the critical role of this pathway in eliciting an appropriate adaptive immune response in the host. Finally, although other fungal pathogens have been shown to elicit IFN-I in mouse models, the specific host cell responsible for producing IFN-I has not been elucidated. We found that CD103+ conventional DCs were the major producer of IFN-I in the lungs of wild-type mice infected with Histoplasma. Mice deficient in this DC subtype displayed reduced IFN-I production in vivo. These data reveal a previously unknown role for CD103+ conventional DCs and uncover the pivotal function of these cells in modulating the host immune response to endemic fungi.

  7. Modelling fungal sink competitiveness with grains for assimilates in wheat infected by a biotrophic pathogen.

    Science.gov (United States)

    Bancal, Marie-Odile; Hansart, Amandine; Sache, Ivan; Bancal, Pierre

    2012-07-01

    Experiments have shown that biotrophic fungi divert assimilates for their growth. However, no attempt has been made either to account for this additional sink or to predict to what extent it competes with both grain filling and plant reserve metabolism for carbon. Fungal sink competitiveness with grains was quantified by a mixed experimental-modelling approach based on winter wheat infected by Puccinia triticina. One week after anthesis, plants grown under controlled conditions were inoculated with varying loads. Sporulation was recorded while plants underwent varying degrees of shading, ensuring a range of both fungal sink and host source levels. Inoculation load significantly increased both sporulating area and rate. Shading significantly affected net assimilation, reserve mobilization and sporulating area, but not grain filling or sporulation rates. An existing carbon partitioning (source-sink) model for wheat during the grain filling period was then enhanced, in which two parameters characterize every sink: carriage capacity and substrate affinity. Fungal sink competitiveness with host sources and sinks was modelled by representing spore production as another sink in diseased wheat during grain filling. Data from the experiment were fitted to the model to provide the fungal sink parameters. Fungal carriage capacity was 0·56 ± 0·01 µg dry matter °Cd(-1) per lesion, much less than grain filling capacity, even in highly infected plants; however, fungal sporulation had a competitive priority for assimilates over grain filling. Simulation with virtual crops accounted for the importance of the relative contribution of photosynthesis loss, anticipated reserve depletion and spore production when light level and disease severity vary. The grain filling rate was less reduced than photosynthesis; however, over the long term, yield loss could double because the earlier reserve depletion observed here would shorten the duration of grain filling. Source-sink modelling

  8. Murine model of disseminated fusariosis: evaluation of the fungal burden by traditional CFU and quantitative PCR.

    Science.gov (United States)

    González, Gloria M; Márquez, Jazmín; Treviño-Rangel, Rogelio de J; Palma-Nicolás, José P; Garza-González, Elvira; Ceceñas, Luis A; Gerardo González, J

    2013-10-01

    Systemic disease is the most severe clinical form of fusariosis, and the treatment involves a challenge due to the refractory response to antifungals. Treatment for murine Fusarium solani infection has been described in models that employ CFU quantitation in organs as a parameter of therapeutic efficacy. However, CFU counts do not precisely reproduce the amount of cells for filamentous fungi such as F. solani. In this study, we developed a murine model of disseminated fusariosis and compared the fungal burden with two methods: CFU and quantitative PCR. ICR and BALB/c mice received an intravenous injection of 1 × 10(7) conidia of F. solani per mouse. On days 2, 5, 7, and 9, mice from each mice strain were killed. The spleen and kidneys of each animal were removed and evaluated by qPCR and CFU determinations. Results from CFU assay indicated that the spleen and kidneys had almost the same fungal burden in both BALB/c and ICR mice during the days of the evaluation. In the qPCR assay, the spleen and kidney of each mouse strain had increased fungal burden in each determination throughout the entire experiment. The fungal load determined by the qPCR assay was significantly greater than that determined from CFU measurements of tissue. qPCR could be considered as a tool for quantitative evaluation of fungal burden in experimental disseminated F. solani infection.

  9. Fungal-Induced Deterioration of Mural Paintings: In Situ and Mock-Model Microscopy Analyses.

    Science.gov (United States)

    Unković, Nikola; Grbić, Milica Ljaljević; Stupar, Miloš; Savković, Željko; Jelikić, Aleksa; Stanojević, Dragan; Vukojević, Jelena

    2016-04-01

    Fungal deterioration of frescoes was studied in situ on a selected Serbian church, and on a laboratory model, utilizing standard and newly implemented microscopy techniques. Scanning electron microscopy (SEM) with energy-dispersive X-ray confirmed the limestone components of the plaster. Pigments used were identified as carbon black, green earth, iron oxide, ocher, and an ocher/cinnabar mixture. In situ microscopy, applied via a portable microscope ShuttlePix P-400R, proved very useful for detection of invisible micro-impairments and hidden, symptomless, microbial growth. SEM and optical microscopy established that observed deterioration symptoms, predominantly discoloration and pulverization of painted layers, were due to bacterial filaments and fungal hyphal penetration, and formation of a wide range of fungal structures (i.e., melanized hyphae, chlamydospores, microcolonial clusters, Cladosporium-like conidia, and Chaetomium perithecia and ascospores). The all year-round monitoring of spontaneous and induced fungal colonization of a "mock painting" in controlled laboratory conditions confirmed the decisive role of humidity level (70.18±6.91% RH) in efficient colonization of painted surfaces, as well as demonstrated increased bioreceptivity of painted surfaces to fungal colonization when plant-based adhesives (ilinocopie, murdent), compared with organic adhesives of animal origin (bone glue, egg white), are used for pigment sizing.

  10. Multiscale Modelling Approach for a Fungal Biofilter Unit for the Hydrophobic Abatement of Volatile Organic Compounds

    DEFF Research Database (Denmark)

    Vergara-Fernández, A.; Rebolledo-Castro, J.; Morales Rodriguez, Ricardo

    2011-01-01

    Currently, biofiltration has become a viable and potential alternative for the treatment of airstreams with low concentrations of hydrophobic volatile organic compounds (VOCs), which can employ to this end, diverse microorganisms (such as, bacteria, fungal or microbial consortia, etc.) growing...... a biofilm. Usually, the design, analysis and scale-up of this kind of units have been mainly done via experimental approach, which can be costly in terms of time and resources. Therefore, the objective of this work is to introduce mathematical model for the prediction and simulation of a fungal biofilter...

  11. Modelling fungal solid-state fermentation: The role of inactivation kinetics

    NARCIS (Netherlands)

    Smits, J.P.; Sonsbeek, H.M. van; Knol, W.; Tramper, J.; Geelhoed, W.; Peeters, M.; Rinzema, A.

    1999-01-01

    The theoretical mathematical models described in this paper are used to evaluate the effects of fungal biomass inactivation kinetics on a non- isothermal tray solid-state fermentation (SSF). The inactivation kinetics, derived from previously reported experiments done under isothermal conditions and

  12. Fungal Sinusitis

    Science.gov (United States)

    ... Marketplace Find an ENT Doctor Near You Fungal Sinusitis Fungal Sinusitis Patient Health Information News media interested ... sinusitis results. There Are Four Types Of Fungal Sinusitis: Mycetoma Fungal Sinusitis produces clumps of spores, a " ...

  13. Pulmonary bacterial and fungal infections in human immunodeficiency virus patients: A study from India

    Directory of Open Access Journals (Sweden)

    K Shreevidya

    2012-01-01

    Full Text Available Background: Human Immunodeficiency Virus (HIV-reactive patients are more prone to infections. The morbidity and mortality in HIV-reactive patients is due to opportunistic infections. Most of the infections seen in Acquired Immunodeficiency Syndrome are endemic to that geographical region. Hence, this study was undertaken to document the occurrence of pulmonary bacterial and fungal infections in HIV patients. Materials and Methods: Expectorated and induced sputum samples were collected from 100 HIV-reactive patients and processed for bacterial and fungal pathogens including Pneumocystis carinii. Results: Of 100 samples, 66 were culture positive. Among the isolates, Mycobacterium tuberculosis constituted the highest number, 55 (83.3%, followed by other bacterial infections, 11 (16.6%, and fungi, 2 (3.03%. Tuberculosis patients had a CD4 count of less than 250 cells/μl with a mean count of 186 cells/μl and those with bacterial infections had a CD4 count of more than 300 cells/μl. The study showed that males were infected with HIV more than females and most of them belonged to the adult age group in the prime of their working life. Weight loss followed by fever and cough were the most common symptoms. Conclusion: M. tuberculosis is the most common opportunistic pathogen followed by bacterial pathogens infecting the lung in HIV. Low CD4 count is a dangerous signal of decreased immune status and higher chances of opportunistic infections and high mortality.

  14. Characterization of the fungal microbiota (mycobiome in healthy and dandruff-afflicted human scalps.

    Directory of Open Access Journals (Sweden)

    Hee Kuk Park

    Full Text Available The human scalp harbors a vast community of microbial mutualists, the composition of which is difficult to elucidate as many of the microorganisms are not culturable using current culture techniques. Dandruff, a common scalp disorder, is known as a causative factor of a mild seborrheic dermatitis as well as pityriasis versicolor, seborrheic dermatitis, and atopic dermatitis. Lipophilic yeast Malassezia is widely accepted to play a role in dandruff, but relatively few comprehensive studies have been reported. In order to investigate fungal biota and genetic resources of dandruff, we amplified the 26S rRNA gene from samples of healthy scalps and dandruff-afflicted scalps. The sequences were analyzed by a high throughput method using a GS-FLX 454 pyrosequencer. Of the 74,811 total sequence reads, Basidiomycota (Filobasidium spp. was the most common phylum associated with dandruff. In contrast, Ascomycota (Acremonium spp. was common in the healthy scalps. Our results elucidate the distribution of fungal communities associated with dandruff and provide new avenues for the potential prevention and treatment of dandruff.

  15. Parasitic, fungal and prion zoonoses: an expanding universe of candidates for human disease.

    Science.gov (United States)

    Akritidis, N

    2011-03-01

    Zoonotic infections have emerged as a burden for millions of people in recent years, owing to re-emerging or novel pathogens often causing outbreaks in the developing world in the presence of inadequate public health infrastructure. Among zoonotic infections, those caused by parasitic pathogens are the ones that affect millions of humans worldwide, who are also at risk of developing chronic disease. The present review discusses the global effect of protozoan pathogens such as Leishmania sp., Trypanosoma sp., and Toxoplasma sp., as well as helminthic pathogens such as Echinococcus sp., Fasciola sp., and Trichinella sp. The zoonotic aspects of agents that are not essentially zoonotic are also discussed. The review further focuses on the zoonotic dynamics of fungal pathogens and prion diseases as observed in recent years, in an evolving environment in which novel patient target groups have developed for agents that were previously considered to be obscure or of minimal significance.

  16. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.

    Science.gov (United States)

    Drewniak, Agata; Gazendam, Roel P; Tool, Anton T J; van Houdt, Michel; Jansen, Machiel H; van Hamme, John L; van Leeuwen, Ester M M; Roos, Dirk; Scalais, Emmanuel; de Beaufort, Carine; Janssen, Hans; van den Berg, Timo K; Kuijpers, Taco W

    2013-03-28

    Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule in the cytosol of myeloid cells, required for induction of T-helper cells producing interleukin-17 (Th17 cells) and important in antifungal immunity. In a patient suffering from Candida dubliniensis meningoencephalitis, mutations in the CARD9 gene were found to result in the loss of protein expression. Apart from the reduced numbers of CD4(+) Th17 lymphocytes, we identified a lack of monocyte-derived cytokines in response to Candida strains. Importantly, CARD9-deficient neutrophils showed a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae. The neutrophil killing defect was independent of the generation of reactive oxygen species by the reduced NAD phosphate oxidase system. Taken together, this demonstrates that human CARD9 deficiency results in selective defect in the host defense against invasive fungal infection, caused by an impaired phagocyte killing.

  17. Fungal metabolites of xanthohumol with potent antiproliferative activity on human cancer cell lines in vitro.

    Science.gov (United States)

    Tronina, Tomasz; Bartmańska, Agnieszka; Filip-Psurska, Beata; Wietrzyk, Joanna; Popłoński, Jarosław; Huszcza, Ewa

    2013-04-01

    Xanthohumol (1) and xanthohumol D (2) were isolated from spent hops. Isoxanthohumol (3) was obtained from xanthohumol by isomerisation in alkaline solution. Six metabolites were obtained as a result of transformation of xanthohumol (1) by selected fungal cultures. Their structures were established on the basis of their spectral data. One of them: 2″-(2'''-hydroxyisopropyl)-dihydrofurano-[4″,5″:3',4']-4',2-dihydroxy-6'-methoxy-α,β-dihydrochalcone (6) has not been previously reported in the literature. The antioxidant properties of hops flavonoids and xanthohumol derivatives were investigated using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The effects of these compounds on proliferation of MCF-7, PC-3 and HT-29 human cancer cell lines were determined by the SRB assay. With the exception of one metabolite, all tested compounds showed antiproliferative activity against the tested human cancer lines. α,β-Dihydroxanthohumol (4), obtained through the biotransformation of xanthohumol, showed higher antiproliferative activity against MCF-7 human breast carcinoma cell line than cisplatin, a widely used anticancer therapeutic agent, and a comparably high activity against PC-3 human prostate cancer cell line.

  18. Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans.

    Directory of Open Access Journals (Sweden)

    Chandrasekaran Komalapriya

    Full Text Available The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C. albicans oxidative stress responses is required for a proper understanding of fungus-host interactions. Therefore, we have adopted an interdisciplinary approach to explore the dynamical responses of C. albicans to hydrogen peroxide (H2O2. Our deterministic mathematical model integrates two major oxidative stress signalling pathways (Cap1 and Hog1 pathways with the three major antioxidant systems (catalase, glutathione and thioredoxin systems and the pentose phosphate pathway, which provides reducing equivalents required for oxidative stress adaptation. The model encapsulates existing knowledge of these systems with new genomic, proteomic, transcriptomic, molecular and cellular datasets. Our integrative approach predicts the existence of alternative states for the key regulators Cap1 and Hog1, thereby suggesting novel regulatory behaviours during oxidative stress. The model reproduces both existing and new experimental observations under a variety of scenarios. Time- and dose-dependent predictions of the oxidative stress responses for both wild type and mutant cells have highlighted the different temporal contributions of the various antioxidant systems during oxidative stress adaptation, indicating that catalase plays a critical role immediately following stress imposition. This is the first model to encapsulate the dynamics of the transcriptional response alongside the redox kinetics of the major antioxidant systems during H2O2 stress in C. albicans.

  19. Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans.

    Science.gov (United States)

    Komalapriya, Chandrasekaran; Kaloriti, Despoina; Tillmann, Anna T; Yin, Zhikang; Herrero-de-Dios, Carmen; Jacobsen, Mette D; Belmonte, Rodrigo C; Cameron, Gary; Haynes, Ken; Grebogi, Celso; de Moura, Alessandro P S; Gow, Neil A R; Thiel, Marco; Quinn, Janet; Brown, Alistair J P; Romano, M Carmen

    2015-01-01

    The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS) that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C. albicans oxidative stress responses is required for a proper understanding of fungus-host interactions. Therefore, we have adopted an interdisciplinary approach to explore the dynamical responses of C. albicans to hydrogen peroxide (H2O2). Our deterministic mathematical model integrates two major oxidative stress signalling pathways (Cap1 and Hog1 pathways) with the three major antioxidant systems (catalase, glutathione and thioredoxin systems) and the pentose phosphate pathway, which provides reducing equivalents required for oxidative stress adaptation. The model encapsulates existing knowledge of these systems with new genomic, proteomic, transcriptomic, molecular and cellular datasets. Our integrative approach predicts the existence of alternative states for the key regulators Cap1 and Hog1, thereby suggesting novel regulatory behaviours during oxidative stress. The model reproduces both existing and new experimental observations under a variety of scenarios. Time- and dose-dependent predictions of the oxidative stress responses for both wild type and mutant cells have highlighted the different temporal contributions of the various antioxidant systems during oxidative stress adaptation, indicating that catalase plays a critical role immediately following stress imposition. This is the first model to encapsulate the dynamics of the transcriptional response alongside the redox kinetics of the major antioxidant systems during H2O2 stress in C. albicans.

  20. Induced Fungal Resistance to Insect Grazing : Reciprocal Fitness Consequences and Fungal Gene Expression in the Drosophila-Aspergillus Model System

    NARCIS (Netherlands)

    Ortiz, Silvia Caballero; Trienens, Monika; Rohlfs, Marko

    2013-01-01

    Background: Fungi are key dietary resources for many animals. Fungi, in consequence, have evolved sophisticated physical and chemical defences for repelling and impairing fungivores. Expression of such defences may entail costs, requiring diversion of energy and nutrients away from fungal growth and

  1. Photostability of natural orange-red and yellow fungal pigments in liquid food model systems.

    Science.gov (United States)

    Mapari, Sameer A S; Meyer, Anne S; Thrane, Ulf

    2009-07-22

    The variation in the photostability among the currently authorized natural pigments limits their application span to a certain type of food system, and more robust alternatives are being sought after to overcome this problem. In the present study, the photostability of an orange-red and a yellow fungal pigment extract produced by ascomycetous fungi belonging to the genera Penicillium and Epicoccum , respectively, were studied in a soft drink model medium and in citrate buffer at low and neutral pH. The quantitative and qualitative color change pattern of the fungal pigment extracts indicated an enhanced photostability of fungal pigment extracts compared to the commercially available natural colorants Monascus Red and turmeric used as controls. Yellow components of the orange-red fungal pigment extract were more photostable than the red components. Chemistry of the photodegradation of the orange-red pigment extract was studied by high-performance liquid chromatography-diode array detection-mass spectrometry (HPLC-DAD-MS), and a light-induced formation of a structural analogue of sequoiamonascin C, a Monascus -like polyketide pigment discovered in the extract of Penicillium aculeatum IBT 14263 on yeast extract sucrose (YES) medium, was confirmed in the soft drink medium at pH 7.

  2. Regulatory network modelling of iron acquisition by a fungal pathogen in contact with epithelial cells

    Directory of Open Access Journals (Sweden)

    Guthke Reinhard

    2010-11-01

    Full Text Available Abstract Background Reverse engineering of gene regulatory networks can be used to predict regulatory interactions of an organism faced with environmental changes, but can prove problematic, especially when focusing on complicated multi-factorial processes. Candida albicans is a major human fungal pathogen. During the infection process, this fungus is able to adapt to conditions of very low iron availability. Such adaptation is an important virulence attribute of virtually all pathogenic microbes. Understanding the regulation of iron acquisition genes will extend our knowledge of the complex regulatory changes during the infection process and might identify new potential drug targets. Thus, there is a need for efficient modelling approaches predicting key regulatory events of iron acquisition genes during the infection process. Results This study deals with the regulation of C. albicans iron uptake genes during adhesion to and invasion into human oral epithelial cells. A reverse engineering strategy is presented, which is able to infer regulatory networks on the basis of gene expression data, making use of relevant selection criteria such as sparseness and robustness. An exhaustive use of available knowledge from different data sources improved the network prediction. The predicted regulatory network proposes a number of new target genes for the transcriptional regulators Rim101, Hap3, Sef1 and Tup1. Furthermore, the molecular mode of action for Tup1 is clarified. Finally, regulatory interactions between the transcription factors themselves are proposed. This study presents a model describing how C. albicans may regulate iron acquisition during contact with and invasion of human oral epithelial cells. There is evidence that some of the proposed regulatory interactions might also occur during oral infection. Conclusions This study focuses on a typical problem in Systems Biology where an interesting biological phenomenon is studied using a small

  3. Induced fungal resistance to insect grazing: reciprocal fitness consequences and fungal gene expression in the Drosophila-Aspergillus model system.

    Directory of Open Access Journals (Sweden)

    Silvia Caballero Ortiz

    Full Text Available BACKGROUND: Fungi are key dietary resources for many animals. Fungi, in consequence, have evolved sophisticated physical and chemical defences for repelling and impairing fungivores. Expression of such defences may entail costs, requiring diversion of energy and nutrients away from fungal growth and reproduction. Inducible resistance that is mounted after attack by fungivores may allow fungi to circumvent the potential costs of defence when not needed. However, no information exists on whether fungi display inducible resistance. We combined organism and fungal gene expression approaches to investigate whether fungivory induces resistance in fungi. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that grazing by larval fruit flies, Drosophila melanogaster, induces resistance in the filamentous mould, Aspergillus nidulans, to subsequent feeding by larvae of the same insect. Larval grazing triggered the expression of various putative fungal resistance genes, including the secondary metabolite master regulator gene laeA. Compared to the severe pathological effects of wild type A. nidulans, which led to 100% insect mortality, larval feeding on a laeA loss-of-function mutant resulted in normal insect development. Whereas the wild type fungus recovered from larval grazing, larvae eradicated the chemically deficient mutant. In contrast, mutualistic dietary yeast, Saccharomyces cerevisiae, reached higher population densities when exposed to Drosophila larval feeding. CONCLUSIONS/SIGNIFICANCE: Our study presents novel evidence that insect grazing is capable of inducing resistance to further grazing in a filamentous fungus. This phenotypic shift in resistance to fungivory is accompanied by changes in the expression of genes involved in signal transduction, epigenetic regulation and secondary metabolite biosynthesis pathways. Depending on reciprocal insect-fungus fitness consequences, fungi may be selected for inducible resistance to maintain high fitness in

  4. Essential metals at the host-pathogen interface: nutritional immunity and micronutrient assimilation by human fungal pathogens.

    Science.gov (United States)

    Crawford, Aaron; Wilson, Duncan

    2015-11-01

    The ability of pathogenic microorganisms to assimilate sufficient nutrients for growth within their hosts is a fundamental requirement for pathogenicity. However, certain trace nutrients, including iron, zinc and manganese, are actively withheld from invading pathogens in a process called nutritional immunity. Therefore, successful pathogenic species must have evolved specialized mechanisms in order to adapt to the nutritionally restrictive environment of the host and cause disease. In this review, we discuss recent advances which have been made in our understanding of fungal iron and zinc acquisition strategies and nutritional immunity against fungal infections, and explore the mechanisms of micronutrient uptake by human pathogenic fungi.

  5. Fungal Biofilms: In Vivo Models for Discovery of Anti-Biofilm Drugs.

    Science.gov (United States)

    Nett, Jeniel E; Andes, David R

    2015-06-01

    During infection, fungi frequently transition to a biofilm lifestyle, proliferating as communities of surface-adherent aggregates of cells. Phenotypically, cells in a biofilm are distinct from free-floating cells. Their high tolerance of antifungals and ability to withstand host defenses are two characteristics that foster resilience. Biofilm infections are particularly difficult to eradicate, and most available antifungals have minimal activity. Therefore, the discovery of novel compounds and innovative strategies to treat fungal biofilms is of great interest. Although many fungi have been observed to form biofilms, the most well-studied is Candida albicans. Animal models have been developed to simulate common Candida device-associated infections, including those involving vascular catheters, dentures, urinary catheters, and subcutaneous implants. Models have also reproduced the most common mucosal biofilm infections: oropharyngeal and vaginal candidiasis. These models incorporate the anatomical site, immune components, and fluid dynamics of clinical niches and have been instrumental in the study of drug resistance and investigation of novel therapies. This chapter describes the significance of fungal biofilm infections, the animal models developed for biofilm study, and how these models have contributed to the development of new strategies for the eradication of fungal biofilm infections.

  6. In vitro Studies on anticancer activity of fungal taxol against human breast cancer cell line MCF-7 cells

    Institute of Scientific and Technical Information of China (English)

    R. Vennila; S. Kamalraj; J. Muthumary

    2012-01-01

    Objective: To prove the anticancer activity of fungal taxol obtained from Pestalotiopsis pauciseta VM1 endophytic fungus of Tabebuia pentaphylla on human breast cancer cell line MCF-7 by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.record ethnobotanical information from a hill-dwelling aboriginal tribe of Odisha. Methods: Different concentrations of fungal taxol ranging from 100 µg to 700 µg were tested against the MCF-7 breast cancer cell line showed significant decrease in the concentration of 350 µg. Results: This cell viability of control cells was consistently 85-90%, The cell shrinkage increased progressively. Conclusions: Thus, the fungal taxol isolated from Pestalotiopsis pauciseta VM1, exhibited a very high degree of in vitro cytotoxic activity against MCF-7 breast cancer cell line.

  7. Gamma, Gaussian and logistic distribution models for airborne pollen grains and fungal spore season dynamics.

    Science.gov (United States)

    Kasprzyk, I; Walanus, A

    2014-01-01

    The characteristics of a pollen season, such as timing and magnitude, depend on a number of factors such as the biology of the plant and environmental conditions. The main aim of this study was to develop mathematical models that explain dynamics in atmospheric concentrations of pollen and fungal spores recorded in Rzeszów (SE Poland) in 2000-2002. Plant taxa with different characteristics in the timing, duration and curve of their pollen seasons, as well as several fungal taxa were selected for this analysis. Gaussian, gamma and logistic distribution models were examined, and their effectiveness in describing the occurrence of airborne pollen and fungal spores was compared. The Gaussian and differential logistic models were very good at describing pollen seasons with just one peak. These are typically for pollen types with just one dominant species in the flora and when the weather, in particular temperature, is stable during the pollination period. Based on s parameter of the Gaussian function, the dates of the main pollen season can be defined. In spite of the fact that seasonal curves are often characterised by positive skewness, the model based on the gamma distribution proved not to be very effective.

  8. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  9. Quantification of fungal growth: models, experiments, and observations

    NARCIS (Netherlands)

    Lamour, A.

    2002-01-01

    This thesis is concerned with the growth of microscopic mycelial fungi (Section I), and that of macroscopic fungi, which form specialised hyphal structures such as rhizomorphs (Section II). A growth model is developed in Section I in relation to soil organic matter decompos

  10. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest.

    Directory of Open Access Journals (Sweden)

    Ferry Hagen

    Full Text Available Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause of several additional case clusters at localities outside of the tropical and subtropical climate zones where the species normally occurs. In every case, the causative agent belongs to a previously rare genotype of C. gattii called AFLP6/VGII, but the origin of the outbreak clades remains enigmatic. Here we used phylogenetic and recombination analyses, based on AFLP and multiple MLST datasets, and coalescence gene genealogy to demonstrate that these outbreaks have arisen from a highly-recombining C. gattii population in the native rainforest of Northern Brazil. Thus the modern virulent C. gattii AFLP6/VGII outbreak lineages derived from mating events in South America and then dispersed to temperate regions where they cause serious infections in humans and animals.

  11. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest.

    Science.gov (United States)

    Hagen, Ferry; Ceresini, Paulo C; Polacheck, Itzhack; Ma, Hansong; van Nieuwerburgh, Filip; Gabaldón, Toni; Kagan, Sarah; Pursall, E Rhiannon; Hoogveld, Hans L; van Iersel, Leo J J; Klau, Gunnar W; Kelk, Steven M; Stougie, Leen; Bartlett, Karen H; Voelz, Kerstin; Pryszcz, Leszek P; Castañeda, Elizabeth; Lazera, Marcia; Meyer, Wieland; Deforce, Dieter; Meis, Jacques F; May, Robin C; Klaassen, Corné H W; Boekhout, Teun

    2013-01-01

    Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause of several additional case clusters at localities outside of the tropical and subtropical climate zones where the species normally occurs. In every case, the causative agent belongs to a previously rare genotype of C. gattii called AFLP6/VGII, but the origin of the outbreak clades remains enigmatic. Here we used phylogenetic and recombination analyses, based on AFLP and multiple MLST datasets, and coalescence gene genealogy to demonstrate that these outbreaks have arisen from a highly-recombining C. gattii population in the native rainforest of Northern Brazil. Thus the modern virulent C. gattii AFLP6/VGII outbreak lineages derived from mating events in South America and then dispersed to temperate regions where they cause serious infections in humans and animals.

  12. Fungal Morphology in Industrial Enzyme Production - Modelling and Monitoring

    DEFF Research Database (Denmark)

    Quintanilla, D.; Hagemann, T.; Hansen, K.

    2015-01-01

    Filamentous fungi are widely used in the biotechnology industry for the production of industrial enzymes. Thus, considerable work has been done with the purpose of characterizing these processes. The ultimate goal of these efforts is to be able to control and predict fermentation performance...... on the basis of "standardized" measurements in terms of morphology, rheology, viscosity, mass transfer and productivity. However, because the variables are connected or dependent on each other, this task is not trivial. The aim of this review article is to gather available information in order to explain......, and on the way the data is interpreted-i.e. which models were applied. The main filamentous fungi used in industrial fermentation are introduced, ranging from Trichoderma reesei to Aspergillus species. Due to the fact that secondary metabolites, like antibiotics, are not to be considered bulk products, organisms...

  13. A modelling framework to simulate foliar fungal epidemics using functional-structural plant models.

    Science.gov (United States)

    Garin, Guillaume; Fournier, Christian; Andrieu, Bruno; Houlès, Vianney; Robert, Corinne; Pradal, Christophe

    2014-09-01

    Sustainable agriculture requires the identification of new, environmentally responsible strategies of crop protection. Modelling of pathosystems can allow a better understanding of the major interactions inside these dynamic systems and may lead to innovative protection strategies. In particular, functional-structural plant models (FSPMs) have been identified as a means to optimize the use of architecture-related traits. A current limitation lies in the inherent complexity of this type of modelling, and thus the purpose of this paper is to provide a framework to both extend and simplify the modelling of pathosystems using FSPMs. Different entities and interactions occurring in pathosystems were formalized in a conceptual model. A framework based on these concepts was then implemented within the open-source OpenAlea modelling platform, using the platform's general strategy of modelling plant-environment interactions and extending it to handle plant interactions with pathogens. New developments include a generic data structure for representing lesions and dispersal units, and a series of generic protocols to communicate with objects representing the canopy and its microenvironment in the OpenAlea platform. Another development is the addition of a library of elementary models involved in pathosystem modelling. Several plant and physical models are already available in OpenAlea and can be combined in models of pathosystems using this framework approach. Two contrasting pathosystems are implemented using the framework and illustrate its generic utility. Simulations demonstrate the framework's ability to simulate multiscaled interactions within pathosystems, and also show that models are modular components within the framework and can be extended. This is illustrated by testing the impact of canopy architectural traits on fungal dispersal. This study provides a framework for modelling a large number of pathosystems using FSPMs. This structure can accommodate both

  14. Fungal microbiota dysbiosis in IBD

    Science.gov (United States)

    Sokol, Harry; Leducq, Valentin; Aschard, Hugues; Pham, Hang-Phuong; Jegou, Sarah; Landman, Cecilia; Cohen, David; Liguori, Giuseppina; Bourrier, Anne; Nion-Larmurier, Isabelle; Cosnes, Jacques; Seksik, Philippe; Langella, Philippe; Skurnik, David; Richard, Mathias L; Beaugerie, Laurent

    2017-01-01

    Objective The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Design Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. Results We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. PMID:26843508

  15. Staurosporine Induces Filamentation in the Human Fungal Pathogen Candida albicans via Signaling through Cyr1 and Protein Kinase A

    Science.gov (United States)

    Xie, Jinglin L.; O’Meara, Teresa R.; Polvi, Elizabeth J.; Robbins, Nicole

    2017-01-01

    ABSTRACT Protein kinases are key regulators of signal transduction pathways that participate in diverse cellular processes. In fungal pathogens, kinases regulate signaling pathways that govern drug resistance, stress adaptation, and pathogenesis. The impact of kinases on the fungal regulatory circuitry has recently garnered considerable attention in the opportunistic fungal pathogen Candida albicans, which is a leading cause of human morbidity and mortality. Complex regulatory circuitry governs the C. albicans morphogenetic transition between yeast and filamentous growth, which is a key virulence trait. Here, we report that staurosporine, a promiscuous kinase inhibitor that abrogates fungal drug resistance, also influences C. albicans morphogenesis by inducing filamentation in the absence of any other inducing cue. We further establish that staurosporine exerts its effect via the adenylyl cyclase Cyr1 and the cyclic AMP (cAMP)-dependent protein kinase A (PKA). Strikingly, filamentation induced by staurosporine does not require the known upstream regulators of Cyr1, Ras1 or Pkc1, or effectors downstream of PKA, including Efg1. We further demonstrate that Cyr1 is capable of activating PKA to enable filamentation in response to staurosporine through a mechanism that does not require degradation of the transcriptional repressor Nrg1. We establish that staurosporine-induced filamentation is accompanied by a defect in septin ring formation, implicating cell cycle kinases as potential staurosporine targets underpinning this cellular response. Thus, we establish staurosporine as a chemical probe to elucidate the architecture of cellular signaling governing fungal morphogenesis and highlight the existence of novel circuitry through which the Cyr1 and PKA govern a key virulence trait. IMPORTANCE The impact of fungal pathogens on human health is devastating. One of the most pervasive fungal pathogens is Candida albicans, which kills ~40% of people suffering from bloodstream

  16. An alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains.

    Science.gov (United States)

    Alcazar-Fuoli, L; Buitrago, Mj; Gomez-Lopez, A; Mellado, E

    2015-01-01

    Aspergillus fumigatus is the most common mold involved in human infections. However, the number of non-fumigatus species able to cause disease is continuously increasing. Among them, Aspergillus lentulus is reported in hematological and cystic fibrosis patients and in those treated with corticosteroids. A. lentulus differs from A. fumigatus in some clinically relevant aspects such as virulence and antifungal susceptibility, showing high MICs to most antifungals. Previous studies proved that A. lentulus was pathogenic in immunocompromised mice, although the course of the infection was delayed compared to A. fumigatus. These differences could explain why A. lentulus is mostly found in mixed infections with A. fumigatus challenging the diagnosis and treatment. We used the alternative model host Galleria mellonella to compare virulence, host interaction, fungal burden and antifungal response when larvae were infected with A. fumigatus or A. lentulus alone, and with a mixture of both species. A. lentulus was pathogenic in G. mellonella but infected larvae did not respond to therapeutic doses of voriconazole. We were able to simultaneously detect A. fumigatus and A. lentulus by a multiplex Nested Real Time PCR (MN-PCR). Comparative analysis of larvae histological sections showed melanization of both species but presented a different pattern of immune response by haemocytes. Analysis of fungal burden and histology showed that A. lentulus survived in the G. mellonella despite the antifungal treatment in single and mixed infections. We conclude that the simultaneous presence of antifungal susceptible and resistant Aspergillus species would likely complicate the management of these infections.

  17. Ecophysiology of ochratoxigenic Aspergillus ochraceus and Penicillium verrucosum isolates. Predictive models for fungal spoilage prevention - a review.

    Science.gov (United States)

    Pardo, E; Marín, S; Ramos, A J; Sanchis, V

    2006-04-01

    Ochratoxin A (OTA) is a secondary metabolite produced by several species of Aspergillus and Penicillium; among them Aspergillus ochraceus and Penicillium verrucosum are two ochratoxigenic species capable of growing in different climates and thus contamination of food crops with OTA can occur worldwide. OTA can be found in a wide range of foods such as cereals, coffee, cocoa, spices, beer, wine, dried vine fruit, grapes and meat products. OTA is toxic to animals, it presents neurotoxic, immunotoxic and nephrotoxic effects. It has been implicated in a human kidney disorder known as Balkan Endemic Nephropathy. This review focuses on the ecophysiology of ochratoxin-producing Aspergillus ochraceus and Penicillium verrucosum, the effect of environmental factors on their germination, mycelial growth, and OTA production. Knowledge of environmental conditions required for sucessive stages of fungal development represent the first step towards preventing mycotoxin formation. Predictive models for different stages of fungal development are presented, which allow prediction of the time before spoilage as a function of the abiotic factors. Finally, the implications of these studies in management of barley, coffee and grapes are described. This can help to identify the critical control points in their production, storage and distribution processes.

  18. Pathogenesis and Antifungal Drug Resistance of the Human Fungal Pathogen Candida glabrata

    Directory of Open Access Journals (Sweden)

    Karl Kuchler

    2011-01-01

    Full Text Available Candida glabrata is a major opportunistic human fungal pathogen causing superficial as well as systemic infections in immunocompromised individuals and several other patient cohorts. C. glabrata represents the second most prevalent cause of candidemia and a better understanding of its virulence and drug resistance mechanisms is thus of high medical relevance. In contrast to the diploid dimorphic pathogen C. albicans, whose ability to undergo filamentation is considered a major virulence trait, C. glabrata has a haploid genome and lacks the ability to switch to filamentous growth. A major impediment for the clinical therapy of C. glabrata infections is its high intrinsic resistance to several antifungal drugs, especially azoles. Further, the development of antifungal resistance, particularly during prolonged and prophylactic therapies is diminishing efficacies of therapeutic interventions. In addition, C. glabrata harbors a large repertoire of adhesins involved in the adherence to host epithelia. Interestingly, genome plasticity, phenotypic switching or the remarkable ability to persist and survive inside host immune cells further contribute to the pathogenicity of C. glabrata. In this comprehensive review, we want to emphasize and discuss the mechanisms underlying virulence and drug resistance of C. glabrata, and discuss its ability to escape from the host immune surveillance or persist inside host cells.

  19. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide.

    Science.gov (United States)

    Bhushan, Shashi; Meyer, Helge; Starosta, Agata L; Becker, Thomas; Mielke, Thorsten; Berninghausen, Otto; Sattler, Michael; Wilson, Daniel N; Beckmann, Roland

    2010-10-08

    Specific regulatory nascent chains establish direct interactions with the ribosomal tunnel, leading to translational stalling. Despite a wealth of biochemical data, structural insight into the mechanism of translational stalling in eukaryotes is still lacking. Here we use cryo-electron microscopy to visualize eukaryotic ribosomes stalled during the translation of two diverse regulatory peptides: the fungal arginine attenuator peptide (AAP) and the human cytomegalovirus (hCMV) gp48 upstream open reading frame 2 (uORF2). The C terminus of the AAP appears to be compacted adjacent to the peptidyl transferase center (PTC). Both nascent chains interact with ribosomal proteins L4 and L17 at tunnel constriction in a distinct fashion. Significant changes at the PTC were observed: the eukaryotic-specific loop of ribosomal protein L10e establishes direct contact with the CCA end of the peptidyl-tRNA (P-tRNA), which may be critical for silencing of the PTC during translational stalling. Our findings provide direct structural insight into two distinct eukaryotic stalling processes.

  20. Regulation of Sterol Biosynthesis in the Human Fungal Pathogen Aspergillus fumigatus: Opportunities for Therapeutic Development

    Science.gov (United States)

    Dhingra, Sourabh; Cramer, Robert A.

    2017-01-01

    Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs). SREBPs regulate transcription of key ergosterol biosynthesis genes in fungi including A. fumigatus. In addition, other emerging regulatory pathways and target genes involved in sterol biosynthesis and drug interactions provide additional opportunities including the unfolded protein response, iron responsive transcriptional networks, and chaperone proteins such as Hsp90. Thus, targeting molecular pathways critical for sterol biosynthesis regulation presents an opportunity to improve therapeutic options for the collection of diseases termed aspergillosis. This mini-review summarizes our current understanding of sterol biosynthesis regulation with a focus on mechanisms of transcriptional regulation by the SREBP family of transcription factors. PMID:28203225

  1. Comparison of reflectance confocal microscopy and two-photon second harmonic generation microscopy in fungal keratitis rabbit model ex vivo

    Science.gov (United States)

    Lee, Jun Ho; Lee, Seunghun; Yoon, Calvin J.; Park, Jin Hyoung; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

    2016-01-01

    Fungal keratitis is an infection of the cornea by fungal pathogens. Diagnosis methods based on optical microscopy could be beneficial over the conventional microbiology method by allowing rapid and non-invasive examination. Reflectance confocal microscopy (RCM) and two-photon second harmonic generation microscopy (TPSHGM) have been applied to pre-clinical or clinical studies of fungal keratitis. In this report, RCM and TPSHGM were characterized and compared in the imaging of a fungal keratitis rabbit model ex vivo. Fungal infection was induced by using two strains of fungi: aspergillus fumigatus and candida albicans. The infected corneas were imaged in fresh condition by both modalities sequentially and their images were analyzed. Both RCM and TPSHGM could detect both fungal strains within the cornea based on morphology: aspergillus fumigatus had distinctive filamentous structures, and candida albicans had round structures superficially and elongated structures in the corneal stroma. These imaging results were confirmed by histology. Comparison between RCM and TPSHGM showed several characteristics. Although RCM and TPSHGM images had good correlation each other, their images were slightly different due to difference in contrast mechanism. RCM had relatively low image contrast with the infected turbid corneas due to high background signal. TPSHGM visualized cells and collagen in the cornea clearly compared to RCM, but used higher laser power to compensate low autofluorescence. Since these two modalities provide complementary information, combination of RCM and TPSHGM would be useful for fungal keratitis detection by compensating their weaknesses each other. PMID:26977371

  2. Fungal diseases: an emerging threat to human, animal, and plant health : workshop summary

    National Research Council Canada - National Science Library

    Olsen, LeighAnne

    2011-01-01

    .... On December 14 and 15, 2010, the IOM's Forum on Microbial Threats hosted a public workshop to explore the scientific and policy dimensions associated with the causes and consequences of emerging fungal diseases...

  3. Crossover fungal pathogens: the biology and pathogenesis of fungi capable of crossing kingdoms to infect plants and humans.

    Science.gov (United States)

    Gauthier, Gregory M; Keller, Nancy P

    2013-12-01

    The outbreak of fungal meningitis associated with contaminated methylprednisolone acetate has thrust the importance of fungal infections into the public consciousness. The predominant pathogen isolated from clinical specimens, Exserohilum rostratum (teleomorph: Setosphaeria rostrata), is a dematiaceous fungus that infects grasses and rarely humans. This outbreak highlights the potential for fungal pathogens to infect both plants and humans. Most crossover or trans-kingdom pathogens are soil saprophytes and include fungi in Ascomycota and Mucormycotina phyla. To establish infection, crossover fungi must overcome disparate, host-specific barriers, including protective surfaces (e.g. cuticle, skin), elevated temperature, and immune defenses. This review illuminates the underlying mechanisms used by crossover fungi to cause infection in plants and mammals, and highlights critical events that lead to human infection by these pathogens. Several genes including veA, laeA, and hapX are important in regulating biological processes in fungi important for both invasive plant and animal infections. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Human sera IgE reacts with a Metarhizium anisopliae fungal catalase

    Science.gov (United States)

    Background: Previous studies have demonstrated that Metarhzium anisopliae extract can induce immune responses in a mouse model that are characteristic of human allergic asthma. Objectives: The objective of this study was to identify and characterize the extract proteins t...

  5. Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

    Energy Technology Data Exchange (ETDEWEB)

    McCluskey, Kevin; Baker, Scott E.

    2017-02-17

    Filamentous fungi have been important as model organisms since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycete filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Similarly, shared data has contributed to the success of model systems. The scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.

  6. Modeling soil organic matter reallocation in soil enhanced by fungal growth

    Science.gov (United States)

    Battaïa, G.; Falconer, R. E.; Otten, W.

    2012-04-01

    Soil, as a huge carbon reservoir having a large interface with the atmosphere, has a major role in understanding global carbon cycle. Yet, its structure gives rise to an extremely complex ecosystem in which chemical fluxes are difficult to describe. Amongst microbial organisms that inhabit soil, fungi represent an entire kingdom of life that has developed its own strategy to adapt its environment. They are thus known to have a particular importance for the reallocation of carbon (and other elements) as they are able to build a mycelium structure that can spread over several meters and through which nutrients can be translocated. This study, based on simulations, is dedicated to enlighten the role of fungal colonization to generate an ecosystem in which coexists disperse biological hotspots. The simulation environment is reconstructed from thresholded computed tomography images of soil samples. Soil organic matter acting as a resource for fungi is assumed to occur first in a particulate solid state (POM). It is degraded into dissolved organic carbon (DOC) through enzymatic activity of fungi. Fungal uptake converts DOC into an internal resource that diffuses through the mycelium and helps it for further colonization. The fungal model is an adaptation of a previously developed model. In addition to internal resource, it accounts for two states of biomass: non-insulated and insulated. One is converted into the other by insulation which is the analog of an ageing process. Being insulated, the interaction rates of the biomass with the environment (degradation and uptake) become slower and the ability to diffuse in the pore space is lost. This aims at producing a more stable state of the mycelium when all resource has been consumed. Spatially simulations reveal a transient state in POM-fungi interaction characterized by a large spread of DOC in the pore space. It is then followed by an enhanced fungal growth toward these areas. Finally a steady state occurs in which DOC

  7. Use of an Artificial Neural Network to Construct a Model of Predicting Deep Fungal Infection in Lung Cancer Patients.

    Science.gov (United States)

    Chen, Jian; Chen, Jie; Ding, Hong-Yan; Pan, Qin-Shi; Hong, Wan-Dong; Xu, Gang; Yu, Fang-You; Wang, Yu-Min

    2015-01-01

    The statistical methods to analyze and predict the related dangerous factors of deep fungal infection in lung cancer patients were several, such as logic regression analysis, meta-analysis, multivariate Cox proportional hazards model analysis, retrospective analysis, and so on, but the results are inconsistent. A total of 696 patients with lung cancer were enrolled. The factors were compared employing Student's t-test or the Mann-Whitney test or the Chi-square test and variables that were significantly related to the presence of deep fungal infection selected as candidates for input into the final artificial neural network analysis (ANN) model. The receiver operating characteristic (ROC) and area under curve (AUC) were used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. The prevalence of deep fungal infection from lung cancer in this entire study population was 32.04%(223/696), deep fungal infections occur in sputum specimens 44.05% (200/454). The ratio of candida albicans was 86.99% (194/223) in the total fungi. It was demonstrated that older (≥65 years), use of antibiotics, low serum albumin concentrations (≤37.18 g /L), radiotherapy, surgery, low hemoglobin hyperlipidemia (≤93.67 g /L), long time of hospitalization (≥14 days) were apt to deep fungal infection and the ANN model consisted of the seven factors. The AUC of ANN model (0.829±0.019) was higher than that of LR model (0.756±0.021). The artificial neural network model with variables consisting of age, use of antibiotics, serum albumin concentrations, received radiotherapy, received surgery, hemoglobin, time of hospitalization should be useful for predicting the deep fungal infection in lung cancer.

  8. Evaluating the Impact of DNA Extraction Method on the Representation of Human Oral Bacterial and Fungal Communities.

    Science.gov (United States)

    Vesty, Anna; Biswas, Kristi; Taylor, Michael W; Gear, Kim; Douglas, Richard G

    2017-01-01

    The application of high-throughput, next-generation sequencing technologies has greatly improved our understanding of the human oral microbiome. While deciphering this diverse microbial community using such approaches is more accurate than traditional culture-based methods, experimental bias introduced during critical steps such as DNA extraction may compromise the results obtained. Here, we systematically evaluate four commonly used microbial DNA extraction methods (MoBio PowerSoil® DNA Isolation Kit, QIAamp® DNA Mini Kit, Zymo Bacterial/Fungal DNA Mini PrepTM, phenol:chloroform-based DNA isolation) based on the following criteria: DNA quality and yield, and microbial community structure based on Illumina amplicon sequencing of the V3-V4 region of the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) 1 region of fungi. Our results indicate that DNA quality and yield varied significantly with DNA extraction method. Representation of bacterial genera in plaque and saliva samples did not significantly differ across DNA extraction methods and DNA extraction method showed no effect on the recovery of fungal genera from plaque. By contrast, fungal diversity from saliva was affected by DNA extraction method, suggesting that not all protocols are suitable to study the salivary mycobiome.

  9. A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Cheryl D Chun

    2007-02-01

    Full Text Available Fungal pathogens of humans require molecular oxygen for several essential biochemical reactions, yet virtually nothing is known about how they adapt to the relatively hypoxic environment of infected tissues. We isolated mutants defective in growth under hypoxic conditions, but normal for growth in normoxic conditions, in Cryptococcus neoformans, the most common cause of fungal meningitis. Two regulatory pathways were identified: one homologous to the mammalian sterol-response element binding protein (SREBP cholesterol biosynthesis regulatory pathway, and the other a two-component-like pathway involving a fungal-specific hybrid histidine kinase family member, Tco1. We show that cleavage of the SREBP precursor homolog Sre1-which is predicted to release its DNA-binding domain from the membrane-occurs in response to hypoxia, and that Sre1 is required for hypoxic induction of genes encoding for oxygen-dependent enzymes involved in ergosterol synthesis. Importantly, mutants in either the SREBP pathway or the Tco1 pathway display defects in their ability to proliferate in host tissues and to cause disease in infected mice, linking for the first time to our knowledge hypoxic adaptation and pathogenesis by a eukaryotic aerobe. SREBP pathway mutants were found to be a hundred times more sensitive than wild-type to fluconazole, a widely used antifungal agent that inhibits ergosterol synthesis, suggesting that inhibitors of SREBP processing could substantially enhance the potency of current therapies.

  10. N-acetylglucosamine increases symptoms and fungal burden in a murine model of oral candidiasis.

    Science.gov (United States)

    Ishijima, Sanae A; Hayama, Kazumi; Takahashi, Miki; Holmes, Ann R; Cannon, Richard D; Abe, Shigeru

    2012-04-01

    The amino sugar N-acetylglucosamine (GlcNAc) is an in vitro inducer of the hyphal mode of growth of the opportunistic pathogen Candida albicans. The development of hyphae by C. albicans is considered to contribute to the pathogenesis of mucosal oral candidiasis. GlcNAc is also a commonly used nutritional supplement for the self-treatment of conditions such as arthritis. To date, no study has investigated whether ingestion of GlcNAc has an effect on the in vivo growth of C. albicans or the pathogenesis of a C. albicans infection. Using a murine model of oral candidiasis, we have found that administration of GlcNAc, but not glucose, increased oral symptoms of candidiasis and fungal burden. Groups of mice were given GlcNAc in either water or in a viscous carrier, i.e., 1% methylcellulose. There was a dose-dependent relationship between GlcNAc concentration and the severity of oral symptoms. Mice given the highest dose of GlcNAc, 45.2 mM, also showed a significant increase in fungal burden, and increased histological evidence of infection compared to controls given water alone. We propose that ingestion of GlcNAc, as a nutritional supplement, may have an impact on oral health in people susceptible to oral candidiasis.

  11. Fungal arthritis

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000444.htm Fungal arthritis To use the sharing features on this page, please enable JavaScript. Fungal arthritis is swelling and irritation (inflammation) of a joint ...

  12. Fungal Meningitis

    Science.gov (United States)

    ... Schedules Preteen & Teen Vaccines Meningococcal Disease Sepsis Fungal Meningitis Language: English Español (Spanish) Recommend on Facebook Tweet ... the brain or spinal cord. Investigation of Fungal Meningitis, 2012 In September 2012, the Centers for Disease ...

  13. Fungal metabolites with anticancer activity.

    Science.gov (United States)

    Evidente, Antonio; Kornienko, Alexander; Cimmino, Alessio; Andolfi, Anna; Lefranc, Florence; Mathieu, Véronique; Kiss, Robert

    2014-05-01

    Covering: 1964 to 2013. Natural products from bacteria and plants have played a leading role in cancer drug discovery resulting in a large number of clinically useful agents. In contrast, the investigations of fungal metabolites and their derivatives have not led to a clinical cancer drug in spite of significant research efforts revealing a large number of fungi-derived natural products with promising anticancer activity. Many of these natural products have displayed notable in vitro growth-inhibitory properties in human cancer cell lines and select compounds have been demonstrated to provide therapeutic benefits in mouse models of human cancer. Many of these compounds are expected to enter human clinical trials in the near future. The present review discusses the reported sources, structures and biochemical studies aimed at the elucidation of the anticancer potential of these promising fungal metabolites.

  14. Fungal genome sequencing: basic biology to biotechnology.

    Science.gov (United States)

    Sharma, Krishna Kant

    2016-08-01

    The genome sequences provide a first glimpse into the genomic basis of the biological diversity of filamentous fungi and yeast. The genome sequence of the budding yeast, Saccharomyces cerevisiae, with a small genome size, unicellular growth, and rich history of genetic and molecular analyses was a milestone of early genomics in the 1990s. The subsequent completion of fission yeast, Schizosaccharomyces pombe and genetic model, Neurospora crassa initiated a revolution in the genomics of the fungal kingdom. In due course of time, a substantial number of fungal genomes have been sequenced and publicly released, representing the widest sampling of genomes from any eukaryotic kingdom. An ambitious genome-sequencing program provides a wealth of data on metabolic diversity within the fungal kingdom, thereby enhancing research into medical science, agriculture science, ecology, bioremediation, bioenergy, and the biotechnology industry. Fungal genomics have higher potential to positively affect human health, environmental health, and the planet's stored energy. With a significant increase in sequenced fungal genomes, the known diversity of genes encoding organic acids, antibiotics, enzymes, and their pathways has increased exponentially. Currently, over a hundred fungal genome sequences are publicly available; however, no inclusive review has been published. This review is an initiative to address the significance of the fungal genome-sequencing program and provides the road map for basic and applied research.

  15. Structure of the dimeric N-glycosylated form of fungal β-N-acetylhexosaminidase revealed by computer modeling, vibrational spectroscopy, and biochemical studies

    Directory of Open Access Journals (Sweden)

    Sklenář Jan

    2007-05-01

    Full Text Available Abstract Background Fungal β-N-acetylhexosaminidases catalyze the hydrolysis of chitobiose into its constituent monosaccharides. These enzymes are physiologically important during the life cycle of the fungus for the formation of septa, germ tubes and fruit-bodies. Crystal structures are known for two monomeric bacterial enzymes and the dimeric human lysosomal β-N-acetylhexosaminidase. The fungal β-N-acetylhexosaminidases are robust enzymes commonly used in chemoenzymatic syntheses of oligosaccharides. The enzyme from Aspergillus oryzae was purified and its sequence was determined. Results The complete primary structure of the fungal β-N-acetylhexosaminidase from Aspergillus oryzae CCF1066 was used to construct molecular models of the catalytic subunit of the enzyme, the enzyme dimer, and the N-glycosylated dimer. Experimental data were obtained from infrared and Raman spectroscopy, and biochemical studies of the native and deglycosylated enzyme, and are in good agreement with the models. Enzyme deglycosylated under native conditions displays identical kinetic parameters but is significantly less stable in acidic conditions, consistent with model predictions. The molecular model of the deglycosylated enzyme was solvated and a molecular dynamics simulation was run over 20 ns. The molecular model is able to bind the natural substrate – chitobiose with a stable value of binding energy during the molecular dynamics simulation. Conclusion Whereas the intracellular bacterial β-N-acetylhexosaminidases are monomeric, the extracellular secreted enzymes of fungi and humans occur as dimers. Dimerization of the fungal β-N-acetylhexosaminidase appears to be a reversible process that is strictly pH dependent. Oligosaccharide moieties may also participate in the dimerization process that might represent a unique feature of the exclusively extracellular enzymes. Deglycosylation had only limited effect on enzyme activity, but it significantly affected

  16. A novel model-based control strategy for aerobic filamentous fungal fed-batch fermentation processes

    DEFF Research Database (Denmark)

    Mears, Lisa; Stocks, Stuart M.; Albaek, Mads O.

    2017-01-01

    A novel model-based control strategy has been developed for filamentous fungal fed-batch fermentation processes. The system of interest is a pilot scale (550 L) filamentous fungus process operating at Novozymes A/S. In such processes, it is desirable to maximize the total product achieved...... in a batch in a defined process time. In order to achieve this goal, it is important to maximize both the product concentration, and also the total final mass in the fed-batch system. To this end, we describe the development of a control strategy which aims to achieve maximum tank fill, while avoiding oxygen...... limited conditions. This requires a two stage approach: (i) calculation of the tank start fill; and (ii) on-line control in order to maximize fill subject to oxygen transfer limitations. First, a mechanistic model was applied off-line in order to determine the appropriate start fill for processes...

  17. Targeting Iron Acquisition Blocks Infection with the Fungal Pathogens Aspergillus fumigatus and Fusarium oxysporum

    Science.gov (United States)

    Leal, Sixto M.; Roy, Sanhita; Vareechon, Chairut; Carrion, Steven deJesus; Clark, Heather; Lopez-Berges, Manuel S.; diPietro, Antonio; Schrettl, Marcus; Beckmann, Nicola; Redl, Bernhard; Haas, Hubertus; Pearlman, Eric

    2013-01-01

    Filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo. Conversely, we show that exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in infected mice. By examining mutant Aspergillus and Fusarium strains, we found that fungal transcriptional responses to low iron levels and extracellular siderophores are essential for fungal growth during infection. Further, we showed that targeting fungal iron acquisition or siderophore biosynthesis by topical application of iron chelators or statins reduces fungal growth in the cornea by 60% and that dual therapy with the iron chelator deferiprone and statins further restricts fungal growth by 75%. Together, these studies identify specific host iron-chelating and fungal iron-acquisition mediators that regulate fungal growth, and demonstrate that therapeutic inhibition of fungal iron acquisition can be utilized to treat topical fungal infections. PMID:23853581

  18. Anti-proliferative effect of fungal taxol extracted from Cladosporium oxysporum against human pathogenic bacteria and human colon cancer cell line HCT 15

    Science.gov (United States)

    Gokul Raj, K.; Manikandan, R.; Arulvasu, C.; Pandi, M.

    2015-03-01

    Cladosporium oxysporum a new taxol producing endophytic fungus was identified and production of taxol were characterized using UV-visible spectroscopy (UV-vis), high-performance liquid chromatography (HPLC), infrared (IR) nuclear magnetic resonance spectroscopy (NMR (13C and 1H)) and liquid chromatography-mass spectrometry (LC-MS). The taxol biosynthetic gene (dbat) was evaluated for new taxol producing fungus. Antibacterial activity against six different human pathogenic bacteria was done by agar well diffusion method. The anticancer efficacy of isolated fungal taxol were also evaluated in human colon cancer cell HCT 15 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cytotoxicity and nuclear morphology analysis. The isolated fungal taxol showed positive towards biosynthetic gene (dbat) and effective against both Gram positive as well as Gram negative. The fungal taxol suppress growth of cancer cell line HCT 15 with an IC50 value of 3.5 μM concentration by 24 h treatment. Thus, the result reveals that C. oxysporum could be a potential alternative source for production of taxol and have antibacterial as well as anticancer properties with possible clinical applications.

  19. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies dif

  20. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  1. Immunodetection of fungal and oomycete pathogens: established and emerging threats to human health, animal welfare and global food security.

    Science.gov (United States)

    Thornton, Christopher R; Wills, Odette E

    2015-02-01

    Filamentous fungi (moulds), yeast-like fungi, and oomycetes cause life-threatening infections of humans and animals and are a major constraint to global food security, constituting a significant economic burden to both agriculture and medicine. As well as causing localized or systemic infections, certain species are potent producers of allergens and toxins that exacerbate respiratory diseases or cause cancer and organ damage. We review the pathogenic and toxigenic organisms that are etiologic agents of both animal and plant diseases or that have recently emerged as serious pathogens of immunocompromised individuals. The use of hybridoma and phage display technologies and their success in generating monoclonal antibodies for the detection and control of fungal and oomycete pathogens are explored. Monoclonal antibodies hold enormous potential for the development of rapid and specific tests for the diagnosis of human mycoses, however, unlike plant pathology, their use in medical mycology remains to be fully exploited.

  2. Fungal DNA barcoding.

    Science.gov (United States)

    Xu, Jianping

    2016-11-01

    Fungi are ubiquitous in both natural and human-made environments. They play important roles in the health of plants, animals, and humans, and in broad ecosystem functions. Thus, having an efficient species-level identification system could significantly enhance our ability to treat fungal diseases and to monitor the spatial and temporal patterns of fungal distributions and migrations. DNA barcoding is a potent approach for rapid identification of fungal specimens, generating novel species hypothesis, and guiding biodiversity and ecological studies. In this mini-review, I briefly summarize (i) the history of DNA sequence-based fungal identification; (ii) the emergence of the ITS region as the consensus primary fungal barcode; (iii) the use of the ITS barcodes to address a variety of issues on fungal diversity from local to global scales, including generating a large number of species hypothesis; and (iv) the problems with the ITS barcode region and the approaches to overcome these problems. Similar to DNA barcoding research on plants and animals, significant progress has been achieved over the last few years in terms of both the questions being addressed and the foundations being laid for future research endeavors. However, significant challenges remain. I suggest three broad areas of research to enhance the usefulness of fungal DNA barcoding to meet the current and future challenges: (i) develop a common set of primers and technologies that allow the amplification and sequencing of all fungi at both the primary and secondary barcode loci; (ii) compile a centralized reference database that includes all recognized fungal species as well as species hypothesis, and allows regular updates from the research community; and (iii) establish a consensus set of new species recognition criteria based on barcode DNA sequences that can be applied across the fungal kingdom.

  3. [Fungal keratitis].

    Science.gov (United States)

    Bourcier, T; Sauer, A; Letscher-Bru, V; Candolfi, E

    2011-10-01

    Fungal keratitis (keratomycosis) is a rare but severe cause of infectious keratitis. Its incidence is constant, due to steroids or immunosuppressive treatments and contact lenses. Pathogens often invade corneas with chronic diseases of the ocular surface but fungal keratitis is also observed following injuries with plant foreign objects. The poor prognosis of these infections is related both to fungal virulence, decreased host defense, as well as delays in diagnosis. However, new antimycotic treatments allow better management and prognosis.

  4. In Silico Phylogenetic Analysis and Molecular Modelling Study of 2-Haloalkanoic Acid Dehalogenase Enzymes from Bacterial and Fungal Origin

    Directory of Open Access Journals (Sweden)

    Raghunath Satpathy

    2016-01-01

    Full Text Available 2-Haloalkanoic acid dehalogenase enzymes have broad range of applications, starting from bioremediation to chemical synthesis of useful compounds that are widely distributed in fungi and bacteria. In the present study, a total of 81 full-length protein sequences of 2-haloalkanoic acid dehalogenase from bacteria and fungi were retrieved from NCBI database. Sequence analysis such as multiple sequence alignment (MSA, conserved motif identification, computation of amino acid composition, and phylogenetic tree construction were performed on these primary sequences. From MSA analysis, it was observed that the sequences share conserved lysine (K and aspartate (D residues in them. Also, phylogenetic tree indicated a subcluster comprised of both fungal and bacterial species. Due to nonavailability of experimental 3D structure for fungal 2-haloalkanoic acid dehalogenase in the PDB, molecular modelling study was performed for both fungal and bacterial sources of enzymes present in the subcluster. Further structural analysis revealed a common evolutionary topology shared between both fungal and bacterial enzymes. Studies on the buried amino acids showed highly conserved Leu and Ser in the core, despite variation in their amino acid percentage. Additionally, a surface exposed tryptophan was conserved in all of these selected models.

  5. Modeling of wind-initiated liberation of fungal propagules from host plant leaves

    Science.gov (United States)

    Gonzalinajec, Trevor

    2014-11-01

    Successful airborne propagule dispersal must begin with liberation into the air. The physical shedding mechanism of airborne propagules in the 100--250 μm size range are not well understood. Many fungal plant pathogens have propagules in this size range that are shed from the bottom of infected leaves. If turbulent air flow is sufficient to liberate the sporocarps of fungi from leaves then the aerodynamic forces exerted must be sufficient to overcome adhesive forces. In this study I have sought to quantify the magnitude and direction of these aerodynamic forces and their causal flow fields with dynamically scaled physical models. I chose a genus of powdery mildew because maturation of the sporocarp entails morphological changes that lever the sporocarp further away from the leaf surface and out of the viscous boundary layer. Consequently I varied the sporocarp morphology, the boundary layer thickness, and the flow velocity as forces on models were measured with a transducer. Additionally I analyzed the fluid velocity around the models using PIV, which allowed for quantification of the relative importance of shear forces and pressure-gradient forces. The results suggest that forces from steady and unsteady wind alike are insufficient to explain liberation.

  6. Unveiling the structural basis for translational ambiguity tolerance in a human fungal pathogen.

    Science.gov (United States)

    Rocha, Rita; Pereira, Pedro José Barbosa; Santos, Manuel A S; Macedo-Ribeiro, Sandra

    2011-08-23

    In a restricted group of opportunistic fungal pathogens the universal leucine CUG codon is translated both as serine (97%) and leucine (3%), challenging the concept that translational ambiguity has a negative impact in living organisms. To elucidate the molecular mechanisms underlying the in vivo tolerance to a nonconserved genetic code alteration, we have undertaken an extensive structural analysis of proteins containing CUG-encoded residues and solved the crystal structures of the two natural isoforms of Candida albicans seryl-tRNA synthetase. We show that codon reassignment resulted in a nonrandom genome-wide CUG redistribution tailored to minimize protein misfolding events induced by the large-scale leucine-to-serine replacement within the CTG clade. Leucine or serine incorporation at the CUG position in C. albicans seryl-tRNA synthetase induces only local structural changes and, although both isoforms display tRNA serylation activity, the leucine-containing isoform is more active. Similarly, codon ambiguity is predicted to shape the function of C. albicans proteins containing CUG-encoded residues in functionally relevant positions, some of which have a key role in signaling cascades associated with morphological changes and pathogenesis. This study provides a first detailed analysis on natural reassignment of codon identity, unveiling a highly dynamic evolutionary pattern of thousands of fungal CUG codons to confer an optimized balance between protein structural robustness and functional plasticity.

  7. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  8. Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  9. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

    Full Text Available Elucidation of pathogenicity mechanisms of the most important human pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections.A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviours in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions.We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modelling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

  10. Analytical framework for modeling of long-range transport of fungal plant epidemics

    Science.gov (United States)

    Kogan, Oleg; O'Keeffe, Kevin; Schneider, David; Myers, Christopher; Analytical FrameworksInfectious Disease Dynamics Team

    2015-03-01

    A new framework for the study of long-range transport of fungal plant epidemics is proposed. The null nonlinear model includes advective transport through the free atmosphere, spore production on the ground, and transfer of spores between the ground and the advective atmospheric layer. The competition between the growth wave on the ground and the effect of the wind is most strongly reflected in upwind fronts, which can propagate into the wind for exponential initial conditions. If the rate of spore transfer into the advective layer is below critical, this happens for initital conditions with arbitrary steepness. Upwind fronts from localized initial conditions will propagate in the direction of the wind above this critical parameter, and will not propagate below it. On the other hand, the speed of the downwind front does not have a strong dependence on the rate of spore transfer between the advective layer and the ground. Thus, even vanishingly small, but finite transfer rates result in a substantial epidemic wave in the direction of the wind. We also consider the effect of an additional, random-walk like mechanism of transport through the near-ground atmospheric boundary layer, and attempt to understand which route dominates the transport over long distances.

  11. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  12. Epigenetic regulation of development and pathogenesis in fungal plant pathogens.

    Science.gov (United States)

    Dubey, Akanksha; Jeon, Junhyun

    2017-08-01

    Evidently, epigenetics is at forefront in explaining the mechanisms underlying the success of human pathogens and in the identification of pathogen-induced modifications within host plants. However, there is a lack of studies highlighting the role of epigenetics in the modulation of the growth and pathogenicity of fungal plant pathogens. In this review, we attempt to highlight and discuss the role of epigenetics in the regulation of the growth and pathogenicity of fungal phytopathogens using Magnaporthe oryzae, a devastating fungal plant pathogen, as a model system. With the perspective of wide application in the understanding of the development, pathogenesis and control of other fungal pathogens, we attempt to provide a synthesized view of the epigenetic studies conducted on M. oryzae to date. First, we discuss the mechanisms of epigenetic modifications in M. oryzae and their impact on fungal development and pathogenicity. Second, we highlight the unexplored epigenetic mechanisms and areas of research that should be considered in the near future to construct a holistic view of epigenetic functioning in M. oryzae and other fungal plant pathogens. Importantly, the development of a complete understanding of the modulation of epigenetic regulation in fungal pathogens can help in the identification of target points to combat fungal pathogenesis. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  13. Arabidopsis thaliana plants expressing human beta-defensin-2 are more resistant to fungal attack: functional homology between plant and human defensins.

    Science.gov (United States)

    Aerts, An M; Thevissen, Karin; Bresseleers, Sara M; Sels, Jan; Wouters, Piet; Cammue, Bruno P A; François, Isabelle E J A

    2007-08-01

    Human beta-defensin-2 (hBD-2) is a small antimicrobial peptide with potent activity against different Gram-negative bacteria and fungal/yeast species. Since human beta-defensins and plant defensins share structural homology, we set out to analyse whether there also exists a functional homology between these defensins of different eukaryotic kingdoms. To this end, we constructed a plant transformation vector harbouring the hBD-2 coding sequence, which we transformed to Arabidopsis thaliana plants, giving rise to A. thaliana plants indeed expressing hBD-2. Furthermore, we could demonstrate that this heterologously produced hBD-2 possesses antifungal activity in vitro. Finally, we could show that hBD-2 expressing A. thaliana plants are more resistant against the broad-spectrum fungal pathogen Botrytis cinerea as compared to untransformed A. thaliana plants, and that this resistance is correlated with the level of active hBD-2 produced in these transgenic plants. Hence, we demonstrated a functional homology, next to the already known structural homology, between defensins originating from different eukaryotic kingdoms. To our knowledge, this is the first time that this is specifically demonstrated for plant and mammalian defensins.

  14. The Black Yeast Exophiala dermatitidis and Other Selected Opportunistic Human Fungal Pathogens Spread from Dishwashers to Kitchens.

    Directory of Open Access Journals (Sweden)

    Jerneja Zupančič

    Full Text Available We investigated the diversity and distribution of fungi in nine different sites inside 30 residential dishwashers. In total, 503 fungal strains were isolated, which belong to 10 genera and 84 species. Irrespective of the sampled site, 83% of the dishwashers were positive for fungi. The most frequent opportunistic pathogenic species were Exophiala dermatitidis, Candida parapsilosis sensu stricto, Exophiala phaeomuriformis, Fusarium dimerum, and the Saprochaete/Magnusiomyces clade. The black yeast E. dermatitidis was detected in 47% of the dishwashers, primarily at the dishwasher rubber seals, at up to 106 CFU/cm2; the other fungi detected were in the range of 102 to 105 CFU/cm2. The other most heavily contaminated dishwasher sites were side nozzles, doors and drains. Only F. dimerum was isolated from washed dishes, while dishwasher waste water contained E. dermatitidis, Exophiala oligosperma and Sarocladium killiense. Plumbing systems supplying water to household appliances represent the most probable route for contamination of dishwashers, as the fungi that represented the core dishwasher mycobiota were also detected in the tap water. Hot aerosols from dishwashers contained the human opportunistic yeast C. parapsilosis, Rhodotorula mucilaginosa and E. dermatitidis (as well as common air-borne genera such as Aspergillus, Penicillium, Trichoderma and Cladosporium. Comparison of fungal contamination of kitchens without and with dishwashers revealed that virtually all were contaminated with fungi. In both cases, the most contaminated sites were the kitchen drain and the dish drying rack. The most important difference was higher prevalence of black yeasts (E. dermatitidis in particular in kitchens with dishwashers. In kitchens without dishwashers, C. parapsilosis strongly prevailed with negligible occurrence of E. dermatitidis. F. dimerum was isolated only from kitchens with dishwashers, while Saprochaete/Magnusiomyces isolates were only found within

  15. The Black Yeast Exophiala dermatitidis and Other Selected Opportunistic Human Fungal Pathogens Spread from Dishwashers to Kitchens.

    Science.gov (United States)

    Zupančič, Jerneja; Novak Babič, Monika; Zalar, Polona; Gunde-Cimerman, Nina

    2016-01-01

    We investigated the diversity and distribution of fungi in nine different sites inside 30 residential dishwashers. In total, 503 fungal strains were isolated, which belong to 10 genera and 84 species. Irrespective of the sampled site, 83% of the dishwashers were positive for fungi. The most frequent opportunistic pathogenic species were Exophiala dermatitidis, Candida parapsilosis sensu stricto, Exophiala phaeomuriformis, Fusarium dimerum, and the Saprochaete/Magnusiomyces clade. The black yeast E. dermatitidis was detected in 47% of the dishwashers, primarily at the dishwasher rubber seals, at up to 106 CFU/cm2; the other fungi detected were in the range of 102 to 105 CFU/cm2. The other most heavily contaminated dishwasher sites were side nozzles, doors and drains. Only F. dimerum was isolated from washed dishes, while dishwasher waste water contained E. dermatitidis, Exophiala oligosperma and Sarocladium killiense. Plumbing systems supplying water to household appliances represent the most probable route for contamination of dishwashers, as the fungi that represented the core dishwasher mycobiota were also detected in the tap water. Hot aerosols from dishwashers contained the human opportunistic yeast C. parapsilosis, Rhodotorula mucilaginosa and E. dermatitidis (as well as common air-borne genera such as Aspergillus, Penicillium, Trichoderma and Cladosporium). Comparison of fungal contamination of kitchens without and with dishwashers revealed that virtually all were contaminated with fungi. In both cases, the most contaminated sites were the kitchen drain and the dish drying rack. The most important difference was higher prevalence of black yeasts (E. dermatitidis in particular) in kitchens with dishwashers. In kitchens without dishwashers, C. parapsilosis strongly prevailed with negligible occurrence of E. dermatitidis. F. dimerum was isolated only from kitchens with dishwashers, while Saprochaete/Magnusiomyces isolates were only found within dishwashers. We

  16. Fungal allergens.

    OpenAIRE

    1995-01-01

    Airborne fungal spores occur widely and often in far greater concentrations than pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal spores induce type I hypersensitivity (allergic) respiratory reactions in sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30% of atopic (allergy-predisposed) individuals or up to 6% of the general population. Diagnosis and immuno...

  17. Fungal osteomyelitis and septic arthritis.

    Science.gov (United States)

    Bariteau, Jason T; Waryasz, Gregory R; McDonnell, Matthew; Fischer, Staci A; Hayda, Roman A; Born, Christopher T

    2014-06-01

    Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in the setting of immunodeficiency and conditions that require immunosuppression. Because fungal osteomyelitis and fungal septic arthritis are rare conditions, study of their pathophysiology and treatment has been limited. In the literature, evidence-based treatment is lacking and, historically, outcomes have been poor. The most common offending organisms are Candida and Aspergillus, which are widely distributed in humans and soil. However, some fungal pathogens, such as Histoplasma, Blastomyces, Coccidioides, Cryptococcus, and Sporothrix, have more focal areas of endemicity. Fungal bone and joint infections result from direct inoculation, contiguous infection spread, or hematogenous seeding of organisms. These infections may be difficult to diagnose and eradicate, especially in the setting of total joint arthroplasty. Although there is no clear consensus on treatment, guidelines are available for management of many of these pathogens.

  18. Elucidating the key role of the fungal mycelium on the biodegradation of n-pentane as a model hydrophobic VOC.

    Science.gov (United States)

    Vergara-Fernández, Alberto; Scott, Felipe; Moreno-Casas, Patricio; Díaz-Robles, Luis; Muñoz, Raúl

    2016-08-01

    The role of the aerial mycelium of the fungus Fusarium solani in the biodegradation of n-pentane was evaluated in a continuous fungal bioreactor (FB) to determine the contribution of the aerial (hyphae) and non-aerial (monolayer) fungal biomass. The experimental results showed that although the aerial biomass fraction represented only 25.9(±3)% on a dry weight basis, it was responsible for 71.6(±4)% of n-pentane removal. The FB attained a maximum elimination capacity (ECmax) of 680(±30) g m(-3) h(-1) in the presence of fungal hyphae (which supported an interfacial area of 5.5(±1.5) × 10(6) m(2) m(-3)). In addition, a mathematical model capable of describing n-pentane biodegradation by the filamentous fungus was also developed and validated against the experimental data. This model successfully predicted the influence of the aerial biomass fraction and its partition coefficient on the n-pentane removal, with EC decreasing from 680(±30) g m(-3) h(-1) to values of 200(±14) g m(-3) h(-1) when the dimensionless partition coefficient increased from 0.21(±0.09) with aerial biomass to 0.88(±0.06) without aerial biomass. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Yeast Biocontrol of a Fungal Plant Disease: A Model for Studying Organism Interrelationships

    Science.gov (United States)

    Chanchaichaovivat, Arun; Panijpan, Bhinyo; Ruenwongsa, Pintip

    2008-01-01

    An experiment on the action of the yeast, "Saccharomyces cerevisiae", against a fungal plant disease is proposed for secondary students (Grade 11) to support their study of organism interrelationship. This biocontrol experiment serves as the basis for discussing relationships among three organisms (red chilli fruit, "Saccharomyces cerevisiae," and…

  20. Yeast Biocontrol of a Fungal Plant Disease: A Model for Studying Organism Interrelationships

    Science.gov (United States)

    Chanchaichaovivat, Arun; Panijpan, Bhinyo; Ruenwongsa, Pintip

    2008-01-01

    An experiment on the action of the yeast, "Saccharomyces cerevisiae", against a fungal plant disease is proposed for secondary students (Grade 11) to support their study of organism interrelationship. This biocontrol experiment serves as the basis for discussing relationships among three organisms (red chilli fruit, "Saccharomyces cerevisiae," and…

  1. Fungal nail infection

    Science.gov (United States)

    Nails - fungal infection; Onychomycosis; Infection - fungal - nails; Tinea unguium ... hair, nails, and outer skin layers. Common fungal infections include: Athlete's foot Jock itch Ringworm on the ...

  2. Protective immune responses to fungal infections.

    Science.gov (United States)

    Rivera, A

    2014-09-01

    The incidence of fungal infections has been on the rise over several decades. Fungal infections threaten animals, plants and humans alike and are thus of significant concern to scientists across disciplines. Over the last decade, significant advances on fungal immunology have lead to a better understanding of important mechanisms of host protection against fungi. In this article, I review recent advances of relevant mechanisms of immune-mediated protection to fungal infections.

  3. Fungal keratitis

    Directory of Open Access Journals (Sweden)

    Sonal S Tuli

    2011-02-01

    Full Text Available Sonal S TuliUniversity of Florida, Gainesville, FL, USA  Clinical question: What is the most appropriate management of fungal keratitis?Results: Traditionally, topical Natamycin is the most commonly used medication for filamentous fungi while Amphotericin B is most commonly used for yeast. Voriconazole is rapidly becoming the drug of choice for all fungal keratitis because of its wide spectrum of coverage and increased penetration into the cornea.Implementation: Repeated debridement of the ulcer is recommended for the penetration of topical medications. While small, peripheral ulcers may be treated in the community, larger or central ulcers, especially if associated with signs suggestive of anterior chamber penetration should be referred to a tertiary center. Prolonged therapy for approximately four weeks is usually necessary.Keywords: fungal keratitis, keratomycosis, antifungal medications, debridement

  4. Tacrolimus (FK506 suppresses TREM-1 expression at an early but not at a late stage in a murine model of fungal keratitis.

    Directory of Open Access Journals (Sweden)

    Weilan Huang

    Full Text Available To investigate the efficacy and mechanism of tacrolimus(FK506, which is a novel macrolide immunosuppressant, in inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1 expression in a murine keratitis model induced by Aspergillus fumigatus.TREM-1 was detected in 11 fungus-infected human corneas by quantitative real-time PCR (qRT-PCR. RAW264.7 macrophages were divided into four groups, which received treatment with zymosan (100 µg/ml, zymosan (100 µg/ml + mTREM-1/Fc protein (1 µg/ml, or zymosan (100 µg/ml + FK506 (20 µM or negative-control treatment. After this treatment, the expression of TREM-1, interleukin-1β (IL-1β and tumor necrosis factor α (TNFα was assayed using qRT-PCR and ELISA. The mouse model of fungal keratitis was created by intrastromal injection with Aspergillus fumigatus, and the mice were divided into 2 groups: group A received vehicle eye drops 4 times each day, and group B received 4 doses of FK506 eye drops each day. Corneal damage was evaluated by clinical scoring and histologic examination,and myeloperoxidase (MPO protein levels were also detected by ELISA. The expression of TREM-1, IL-1β and TNFα was then determined at different time points using qRT-PCR and ELISA.TREM-1 expression dramatically increased in the human corneas with fungal keratitis. In contrast, FK506 reduced the expression of TREM-1, IL-1β and TNFα in RAW264.7 macrophages stimulated with zymosan. In the mouse model, at day 1 post-infection, the corneal score of the FK506-treated group was lower than that of the control, and polymorphonuclear neutrophil (PMN infiltration was diminished. TREM-1, IL-1β and TNFα expression was significantly reduced at the same time point. However, the statistically significant differences in cytokine expression, clinical scores and infiltration disappeared at 5 days post-infection.FK506 may inhibit the inflammation induced by fungi and alleviate the severity of corneal damage at an early stage of

  5. The Fungal Sexual Pheromone Sirenin Activates the Human CatSper Channel Complex.

    Science.gov (United States)

    Syeda, Shameem Sultana; Carlson, Erick J; Miller, Melissa R; Francis, Rawle; Clapham, David E; Lishko, Polina V; Hawkinson, Jon E; Hook, Derek; Georg, Gunda I

    2016-02-19

    The basal fungus Allomyces macrogynus (A. macrogynus) produces motile male gametes displaying well-studied chemotaxis toward their female counterparts. This chemotaxis is driven by sirenin, a sexual pheromone released by the female gametes. The pheromone evokes a large calcium influx in the motile gametes, which could proceed through the cation channel of sperm (CatSper) complex. Herein, we report the total synthesis of sirenin in 10 steps and 8% overall yield and show that the synthetic pheromone activates the CatSper channel complex, indicated by a concentration-dependent increase in intracellular calcium in human sperm. Sirenin activation of the CatSper channel was confirmed using whole-cell patch clamp electrophysiology with human sperm. Based on this proficient synthetic route and confirmed activation of CatSper, analogues of sirenin can be designed as blockers of the CatSper channel that could provide male contraceptive agents.

  6. Fungal prions.

    Science.gov (United States)

    Staniforth, Gemma L; Tuite, Mick F

    2012-01-01

    For both mammalian and fungal prion proteins, conformational templating drives the phenomenon of protein-only infectivity. The conformational conversion of a protein to its transmissible prion state is associated with changes to host cellular physiology. In mammals, this change is synonymous with disease, whereas in fungi no notable detrimental effect on the host is typically observed. Instead, fungal prions can serve as epigenetic regulators of inheritance in the form of partial loss-of-function phenotypes. In the presence of environmental challenges, the prion state [PRION(+)], with its resource for phenotypic plasticity, can be associated with a growth advantage. The growing number of yeast proteins that can switch to a heritable [PRION(+)] form represents diverse and metabolically penetrating cellular functions, suggesting that the [PRION(+)] state in yeast is a functional one, albeit rarely found in nature. In this chapter, we introduce the biochemical and genetic properties of fungal prions, many of which are shared by the mammalian prion protein PrP, and then outline the major contributions that studies on fungal prions have made to prion biology.

  7. Fungal Entomopathogens

    Science.gov (United States)

    Fungal entomopathogens are important biological control agents worldwide and have been the subject of intense research for more than100 years. They exhibit both sexual and asexual reproduction and produce different types of infective propagules. Their mode of action against insects involves attachme...

  8. The MAP kinase-activated protein kinase Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen Candida albicans.

    Science.gov (United States)

    Li, Xichuan; Du, Wei; Zhao, Jingwen; Zhang, Lilin; Zhu, Zhiyan; Jiang, Linghuo

    2010-06-01

    Rck2p is the Hog1p-MAP kinase-activated protein kinase required for the attenuation of protein synthesis in response to an osmotic challenge in Saccharomyces cerevisiae. Rck2p also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. In this study, we demonstrate that the deletion of CaRCK2 renders C. albicans cells sensitive to, and CaRck2p translocates from the cytosol to the nucleus in response to, cell wall stresses caused by Congo red, Calcoflor White, elevated heat and zymolyase. However, the kinase activity of CaRck2p is not required for the cellular response to these cell wall stresses. Furthermore, transcripts of cell wall protein-encoding genes CaBGL2, CaHWP1 and CaXOG1 are reduced in C. albicans cells lacking CaRCK2. The deletion of CaRCK2 also reduces the in vitro filamentation of C. albicans and its virulence in a mouse model of systemic candidasis. The kinase activity of CaRck2p is required for the virulence, but not for the in vitro filamentation, in C. albicans. Therefore, Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen C. albicans.

  9. Proteomic analysis of the secretions of Pseudallescheria boydii, a human fungal pathogen with unknown genome.

    Science.gov (United States)

    da Silva, Bianca Alcântara; Sodré, Cátia Lacerda; Souza-Gonçalves, Ana Luiza; Aor, Ana Carolina; Kneipp, Lucimar Ferreira; Fonseca, Beatriz Bastos; Rozental, Sonia; Romanos, Maria Teresa Villela; Sola-Penna, Mauro; Perales, Jonas; Kalume, Dário Eluan; dos Santos, André Luis Souza

    2012-01-01

    Pseudallescheria boydii is a filamentous fungus that causes a wide array of infections that can affect practically all the organs of the human body. The treatment of pseudallescheriosis is difficult since P. boydii exhibits intrinsic resistance to the majority of antifungal drugs used in the clinic and the virulence attributes expressed by this fungus are unknown. The study of the secretion of molecules is an important approach for understanding the pathogenicity of fungi. With this task in mind, we have shown that mycelial cells of P. boydii were able to actively secrete proteins into the extracellular environment; some of them were recognized by antibodies present in the serum of a patient with pseudallescheriosis. Additionally, molecules secreted by P. boydii induced in vitro irreversible damage in pulmonary epithelial cells. Subsequently, two-dimensional gel electrophoresis combined with mass spectrometry was carried out in order to start the construction of a map of secreted proteins from P. boydii mycelial cells. The two-dimensional map showed that most of the proteins (around 100 spots) were focused at pH ranging from 4 to 7 with molecular masses ranging from 14 to >117 kDa. Fifty spots were randomly selected, of which 30 (60%) were consistently identified, while 20 (40%) spots generated peptides that showed no resemblance to any known protein from other fungi and/or MS with low quality. Notably, we identified proteins involved in metabolic pathways (energy/carbohydrate, nucleotide, and fatty acid), cell wall remodeling, RNA processing, signaling, protein degradation/nutrition, translation machinery, drug elimination and/or detoxification, protection against environmental stress, cytoskeleton/movement proteins, and immunogenic molecules. Since the genome of this fungus is not sequenced, we performed enzymatic and immunodetection assays in order to corroborate the presence of some released proteins. The identification of proteins actively secreted by P

  10. The anti-biofilm potential of pomegranate (Punica granatum L.) extract against human bacterial and fungal pathogens.

    Science.gov (United States)

    Bakkiyaraj, Dhamodharan; Nandhini, Janarthanam Rathna; Malathy, Balakumar; Pandian, Shunmugiah Karutha

    2013-09-01

    Infectious diseases caused by bacteria and fungi are the major cause of morbidity and mortality across the globe. Multi-drug resistance in these pathogens augments the complexity and severity of the diseases. Various studies have shown the role of biofilms in multi-drug resistance, where the pathogen resides inside a protective coat made of extracellular polymeric substances. Since biofilms directly influence the virulence and pathogenicity of a pathogen, it is optimal to employ a strategy that effectively inhibits the formation of biofilm. Pomegranate is a common food and is also used traditionally to treat various ailments. This study assessed the anti-biofilm activity of a methanolic extract of pomegranate against bacterial and fungal pathogens. Methanolic extract of pomegranate was shown to inhibit the formation of biofilms by Staphylococcus aureus, methicillin resistant S. aureus, Escherichia coli, and Candida albicans. Apart from inhibiting the formation of biofilm, pomegranate extract disrupted pre-formed biofilms and inhibited germ tube formation, a virulence trait, in C. albicans. Characterization of the methanolic extract of pomegranate revealed the presence of ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione) as the major component. Ellagic acid is a bioactive tannin known for its antioxidant, anticancer, and anti-inflammatory properties. Further studies revealed the ability of ellagic acid to inhibit the growth of all species in suspension at higher concentrations (>75 μg ml(-1)) and biofilm formation at lower concentrations (pomegranate for the treatment of human ailments.

  11. Combined effects of fungal alkaloids on intestinal motility in an in vitro rat model.

    Science.gov (United States)

    Dalziel, J E; Dunstan, K E; Finch, S C

    2013-11-01

    Diarrhea is caused by factors that alter absorption and secretion of water and ions across the intestinal epithelium and disrupt motility. Parasitic infection, stress, poor nutrition, and exposure to plant or fungal toxins predispose livestock to noninfectious diarrhea. This is more prevalent in sheep that graze pastures infected with wild-type endophytic fungus, suggesting the involvement of fungal alkaloids. These increase smooth muscle contraction: ergovaline/ergotamine (ergot alkaloid) activates serotonin (5-HT) receptors, and lolitrem B (indole diterpene) inhibits large-conductance Ca2+-activated K+ (BK) channels. Because of their separate mechanisms of action the objective of this study was to investigate whether they act synergistically to increase smooth muscle contraction. Effects of ergotamine (1 µM) and lolitrem B (0.1 µM) on the tension and frequency of spontaneous contractions were investigated in a longitudinal preparation of isolated distal colon. The compounds were dissolved in 0.1% dimethyl sulfoxide (DMSO) and applied separately or together for 1 h. Ergotamine increased contractile tension compared to the pretreatment control (Pergotamine alone. The increased contractile tension when both compounds were applied together indicates that ergotamine and lolitrem B acted synergistically to increase smooth muscle contraction, suggesting that they would alter motility in vivo.

  12. Galleria mellonella as a model host for human pathogens

    Science.gov (United States)

    Junqueira, Juliana Campos

    2012-01-01

    The number of studies using G. mellonella as a model host for human pathogens has increased significantly in the last few years. Important studies were published from different countries for evaluating the pathogenesis of bacterial and fungal infections and for exploring the host defenses against pathogens. Therefore, standardized conditions for the use of G. melonella larvae need to be established. Recent research showed that the deprivation of G. mellonella larvae of food during the experiment caused a reduction in immune responses and an increased susceptibility to infection, suggesting that incubating of larvae in the presence or absence of nutrition may affect the results and comparisons among different laboratories. PMID:23211681

  13. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  14. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  15. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  16. Predicting invasive fungal pathogens using invasive pest assemblages: testing model predictions in a virtual world.

    Directory of Open Access Journals (Sweden)

    Dean R Paini

    Full Text Available Predicting future species invasions presents significant challenges to researchers and government agencies. Simply considering the vast number of potential species that could invade an area can be insurmountable. One method, recently suggested, which can analyse large datasets of invasive species simultaneously is that of a self organising map (SOM, a form of artificial neural network which can rank species by establishment likelihood. We used this method to analyse the worldwide distribution of 486 fungal pathogens and then validated the method by creating a virtual world of invasive species in which to test the SOM. This novel validation method allowed us to test SOM's ability to rank those species that can establish above those that can't. Overall, we found the SOM highly effective, having on average, a 96-98% success rate (depending on the virtual world parameters. We also found that regions with fewer species present (i.e. 1-10 species were more difficult for the SOM to generate an accurately ranked list, with success rates varying from 100% correct down to 0% correct. However, we were able to combine the numbers of species present in a region with clustering patterns in the SOM, to further refine confidence in lists generated from these sparsely populated regions. We then used the results from the virtual world to determine confidences for lists generated from the fungal pathogen dataset. Specifically, for lists generated for Australia and its states and territories, the reliability scores were between 84-98%. We conclude that a SOM analysis is a reliable method for analysing a large dataset of potential invasive species and could be used by biosecurity agencies around the world resulting in a better overall assessment of invasion risk.

  17. Predicting Invasive Fungal Pathogens Using Invasive Pest Assemblages: Testing Model Predictions in a Virtual World

    Science.gov (United States)

    Paini, Dean R.; Bianchi, Felix J. J. A.; Northfield, Tobin D.; De Barro, Paul J.

    2011-01-01

    Predicting future species invasions presents significant challenges to researchers and government agencies. Simply considering the vast number of potential species that could invade an area can be insurmountable. One method, recently suggested, which can analyse large datasets of invasive species simultaneously is that of a self organising map (SOM), a form of artificial neural network which can rank species by establishment likelihood. We used this method to analyse the worldwide distribution of 486 fungal pathogens and then validated the method by creating a virtual world of invasive species in which to test the SOM. This novel validation method allowed us to test SOM's ability to rank those species that can establish above those that can't. Overall, we found the SOM highly effective, having on average, a 96–98% success rate (depending on the virtual world parameters). We also found that regions with fewer species present (i.e. 1–10 species) were more difficult for the SOM to generate an accurately ranked list, with success rates varying from 100% correct down to 0% correct. However, we were able to combine the numbers of species present in a region with clustering patterns in the SOM, to further refine confidence in lists generated from these sparsely populated regions. We then used the results from the virtual world to determine confidences for lists generated from the fungal pathogen dataset. Specifically, for lists generated for Australia and its states and territories, the reliability scores were between 84–98%. We conclude that a SOM analysis is a reliable method for analysing a large dataset of potential invasive species and could be used by biosecurity agencies around the world resulting in a better overall assessment of invasion risk. PMID:22016773

  18. The cell recognition model in chlorolichens involving a fungal lectin binding to an algal ligand can be extended to cyanolichens.

    Science.gov (United States)

    Vivas, M; Sacristán, M; Legaz, M E; Vicente, C

    2010-07-01

    Leptogium corniculatum, a cyanolichen containing Nostoc as photobiont, produces and secretes arginase to culture medium containing arginine. This secreted arginase was pre-purified by affinity chromatography on beads of activated agarose to which a polygalactosylated urease, purified from Evernia prunastri, was attached. Arginase was eluted from the beads with 50 mm alpha-d-galactose. The eluted arginase binds preferentially to the cell surface of Nostoc isolated from this lichen thallus, although it is also able to bind, to some extent, to the cell surface of the chlorobiont isolated from E. prunastri. Previous studies in chlorolichens have shown that a fungal lectin that develops subsidiary arginase activity can be a factor in recognition of compatible algal cells through binding to a polygalactosylated urease, which acts as a lectin ligand in the algal cell wall. Our experiments demonstrate that this model can now be extended to cyanolichens.

  19. The anti-inflammatory fungal compound (S)-curvularin reduces proinflammatory gene expression in an in vivo model of rheumatoid arthritis.

    Science.gov (United States)

    Schmidt, Nadine; Art, Julia; Forsch, Ingrid; Werner, Anke; Erkel, Gerhard; Jung, Mathias; Horke, Sven; Kleinert, Hartmut; Pautz, Andrea

    2012-10-01

    In previous studies, we identified the fungal macrocyclic lactone (S)-curvularin (SC) as an anti-inflammatory agent using a screening system detecting inhibitors of the Janus kinase/signal transducer and activator of transcription pathway. The objective of the present study was to investigate whether SC is able to decrease proinflammatory gene expression in an in vivo model of a chronic inflammatory disease. Therefore, the effects of SC and dexamethasone were compared in the model of collagen-induced arthritis (CIA) in mice. Total genomic microarray analyses were performed to identify SC target genes. In addition, in human C28/I2 chondrocytes and MonoMac6 monocytes, the effect of SC on proinflammatory gene expression was tested at the mRNA and protein level. In the CIA model, SC markedly reduced the expression of a number of proinflammatory cytokines and chemokines involved in the pathogenesis of CIA as well as human rheumatoid arthritis (RA). In almost all cases, the effects of SC were comparable with those of dexamethasone. In microarray analyses, we identified additional new therapeutic targets of SC. Some of them, such as S100A8, myeloperoxidase, or cathelicidin, an antimicrobial peptide, are known to be implicated in pathophysiological processes in RA. Similar anti-inflammatory effects of SC were also observed in human C28/I2 chondrocyte cells, which are resistant to glucocorticoid treatment. These data indicate that SC and glucocorticoid effects are mediated via independent signal transduction pathways. In summary, we demonstrate that SC is a new effective anti-inflammatory compound that may serve as a lead compound for the development of new drugs for the therapy of chronic inflammatory diseases.

  20. Fungal Eye Infections

    Science.gov (United States)

    ... Treatment & Outcomes Statistics More Resources Fungal Nail Infections Histoplasmosis Definition Symptoms People at Risk & Prevention Sources Diagnosis & ... CDC at Work Global Fungal Diseases Cryptococcal Meningitis Histoplasmosis ... Resistance Resources Laboratory Submission Information Reportable Fungal ...

  1. Opportunistic invasive fungal pathogen Macrophomina phaseolina prognosis from immunocompromised humans to potential mitogenic RBL with an exceptional and novel antitumor and cytotoxic effect.

    Science.gov (United States)

    Arora, P; Dilbaghi, N; Chaudhury, A

    2012-02-01

    With the ever-increasing risk for fungal infections, one can no longer ignore fungi. It is imperative that clinical manifestations "presume fungus" with their epidemiologic and pathogenic features when evaluating a potentially infected patient. In the high-risk patient groups, fungi with intrinsic resistance to antifungal agents already exist, with a tendency to emerge as opportunistic pathogens. One of the smart pathogens is Macrophomina phaseolina, with the potential to disarm plant, animal, and human immunity. The response prophylaxis may vary from antifungal therapy and surgical measures to biochemical (Rhizoctonia bataticola lectin [RBL] with antitumor and cytotoxic nature) and gene therapeutics.

  2. Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi

    Directory of Open Access Journals (Sweden)

    Ana M. Pinheiro

    2017-06-01

    Full Text Available The lack of antifungal drugs with novel modes of action reaching the clinic is a serious concern. Recently a novel antifungal protein referred to as Blad-containing oligomer (BCO has received regulatory approval as an agricultural antifungal agent. Interestingly its spectrum of antifungal activity includes human pathogens such as Candida albicans, however, its mode of action has yet to be elucidated. Here we demonstrate that BCO exerts its antifungal activity through inhibition of metal ion homeostasis which results in apoptotic cell death in C. albicans. HIP HOP profiling in Saccharomyces cerevisiae using a panel of signature strains that are characteristic for common modes of action identified hypersensitivity in yeast lacking the iron-dependent transcription factor Aft1 suggesting restricted iron uptake as a mode of action. Furthermore, global transcriptome profiling in C. albicans also identified disruption of metal ion homeostasis as a potential mode of action. Experiments were carried out to assess the effect of divalent metal ions on the antifungal activity of BCO revealing that BCO activity is antagonized by metal ions such as Mn2+, Zn2+, and Fe2+. The transcriptome profile also implicated sterol synthesis as a possible secondary mode of action which was subsequently confirmed in sterol synthesis assays in C. albicans. Animal models for toxicity showed that BCO is generally well tolerated and presents a promising safety profile as a topical applied agent. Given its potent broad spectrum antifungal activity and novel multitarget mode of action, we propose BCO as a promising new antifungal agent for the topical treatment of fungal infections.

  3. Identification and Evaluation of Novel Drug Targets against the Human Fungal Pathogen Aspergillus fumigatus with Elaboration on the Possible Role of RNA-Binding Protein

    Science.gov (United States)

    Malekzadeh, Saeid; Sardari, Soroush; Azerang, Parisa; Khorasanizadeh, Dorsa; Amiri, Solmaz Agha; Azizi, Mohammad; Mohajerani, Nazanin; Khalaj, Vahid

    2017-01-01

    Bakground: Aspergillus fumigatus is an airborne opportunistic fungal pathogen that can cause fatal infections in immunocompromised patients. Although the current anti-fungal therapies are relatively efficient, some issues such as drug toxicity, drug interactions, and the emergence of drug-resistant fungi have promoted the intense research toward finding the novel drug targets. Methods: In search of new antifungal drug targets, we have used a bioinformatics approach to identify novel drug targets. We compared the whole proteome of this organism with yeast Saccharomyces cerevisiae to come up with 153 specific proteins. Further screening of these proteins revealed 50 potential molecular targets in A. fumigatus. Amongst them, RNA-binding protein (RBP) was selected for further examination. The aspergillus fumigatus RBP (AfuRBP), as a peptidylprolyl isomerase, was evaluated by homology modeling and bioinformatics tools. RBP-deficient mutant strains of A. fumigatus were generated and characterized. Furthermore, the susceptibility of these strains to known peptidylprolyl isomerase inhibitors was assessed. Results: AfuRBP-deficient mutants demonstrated a normal growth phenotype. MIC assay results using inhibitors of peptidylprolyl isomerase confirmed a higher sensitivity of these mutants compared to the wild type. Conclusion: Our bioinformatics approach revealed a number of fungal-specific proteins that may be considered as new targets for drug discovery purposes. Peptidylprolyl isomerase, as a possible drug target, was evaluated against two potential inhibitors, and the promising results were investigated mechanistically. Future studies would confirm the impact of such target on the antifungal discovery investigations PMID:28000798

  4. Fungal genomics beyond Saccharomyces cerevisiae?

    DEFF Research Database (Denmark)

    Hofmann, Gerald; Mcintyre, Mhairi; Nielsen, Jens

    2003-01-01

    Fungi are used extensively in both fundamental research and industrial applications. Saccharomyces cerevisiae has been the model organism for fungal research for many years, particularly in functional genomics. However, considering the diversity within the fungal kingdom, it is obvious that the a......Fungi are used extensively in both fundamental research and industrial applications. Saccharomyces cerevisiae has been the model organism for fungal research for many years, particularly in functional genomics. However, considering the diversity within the fungal kingdom, it is obvious...... that the application of the existing methods of genome, transcriptome, proteome and metabolome analysis to other fungi has enormous potential, especially for the production of food and food ingredients. The developments in the past year demonstrate that we have only just started to exploit this potential....

  5. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived......, thereby implying that interactions between spreading processes are driving forces of attention dynamics. Overall, the thesis contributes to a quantitative understanding of a wide range of different human behaviors by applying mathematical modeling to behavioral data. There can be no doubt......During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...

  6. Development and application of predictive models for fungal growth as tools to improve quality control in yogurt production.

    Science.gov (United States)

    Gougouli, Maria; Kalantzi, Kelly; Beletsiotis, Evangelos; Koutsoumanis, Konstantinos P

    2011-12-01

    The effect of storage temperature (0-40 °C) and inoculum size (10¹-10⁵ spores) on the mycelium growth kinetics of 12 fungal species on yogurt were monitored. A cardinal model with inflection (CMI) was used to describe the effect of temperature on the growth rate (μ) and the lag time (λ) of each isolate. Significant differences on the temperature dependence of the mycelium growth between the tested species were observed. Depending on the strain, the estimated minimum, optimum and maximum temperature parameters for μ (T(min), T(opt), T(max)) ranged from -7.6 to 9.6, 19.5 to 37.8 and 29.8 to 46.9 °C, respectively. Only λ was found to be affected by the inoculum size and a linear relation between Ln (λ) and Log (inoculum size) was revealed. The inoculum level did not influence the values of T(min), T(opt) and T(max) for λ. Based on the above observations, the combined effect of inoculum size and temperature on λ was modeled using a modified CMI. The parameter λ(opt) (λ at optimum conditions) was expressed as a function of the inoculum size. Validation studies showed a good performance of the developed models. The application scheme of the models for improving fungi control in yogurt productions is discussed.

  7. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on obs

  8. Brachypodium distachyon-Cochliobolus sativus Pathosystem is a New Model for Studying Plant-Fungal Interactions in Cereal Crops.

    Science.gov (United States)

    Zhong, Shaobin; Ali, Shaukat; Leng, Yueqiang; Wang, Rui; Garvin, David F

    2015-04-01

    Cochliobolus sativus (anamorph: Bipolaris sorokiniana) causes spot blotch, common root rot, and kernel blight or black point in barley and wheat. However, little is known about the molecular mechanisms underlying the pathogenicity of C. sativus or the molecular basis of resistance and susceptibility in the hosts. This study aims to establish the model grass Brachypodium distachyon as a new model for studying plant-fungus interactions in cereal crops. Six B. distachyon lines were inoculated with five C. sativus isolates. The results indicated that all six B. distachyon lines were infected by the C. sativus isolates, with their levels of resistance varying depending on the fungal isolates used. Responses ranging from hypersensitive response-mediated resistance to complete susceptibility were observed in a large collection of B. distachyon (2n=2x=10) and B. hybridum (2n=4x=30) accessions inoculated with four of the C. sativus isolates. Evaluation of an F2 population derived from the cross between two of the B. distachyon lines, Bd1-1 and Bd3-1, with isolate Cs07-47-1 showed quantitative and transgressive segregation for resistance to C. sativus, suggesting that the resistance may be governed by quantitative trait loci from both parents. The availability of whole-genome sequences of both the host (B. distachyon) and the pathogen (C. sativus) makes this pathosystem an attractive model for studying this important disease of cereal crops.

  9. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...... studies have considered data sets with just one behavioral variable such as email communication. The Social Fabric interdisciplinary research project is an attempt to collect a more complete data set on human behavior by providing 1000 smartphones with pre-installed data collection software to students...... data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived...

  10. The natural diyne-furan fatty acid EV-086 is an inhibitor of fungal delta-9 fatty acid desaturation with efficacy in a model of skin dermatophytosis.

    Science.gov (United States)

    Knechtle, Philipp; Diefenbacher, Melanie; Greve, Katrine B V; Brianza, Federico; Folly, Christophe; Heider, Harald; Lone, Museer A; Long, Lisa; Meyer, Jean-Philippe; Roussel, Patrick; Ghannoum, Mahmoud A; Schneiter, Roger; Sorensen, Alexandra S

    2014-01-01

    Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity in vitro against Candida, Aspergillus, and Trichophyton spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of Saccharomyces cerevisiae deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in S. cerevisiae, depending on the delta-9 fatty acid desaturase OLE1. Delta-9 unsaturated fatty acids-but not saturated fatty acids-antagonized the EV-086-mediated growth inhibition, and transcription of the OLE1 gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086-phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical Trichophyton infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses.

  11. Fungal prion HET-s as a model for structural complexity and self-propagation in prions.

    Science.gov (United States)

    Wan, William; Stubbs, Gerald

    2014-04-01

    The highly ordered and reproducible structure of the fungal prion HET-s makes it an excellent model system for studying the inherent properties of prions, self-propagating infectious proteins that have been implicated in a number of fatal diseases. In particular, the HET-s prion-forming domain readily folds into a relatively complex two-rung β-solenoid amyloid. The faithful self-propagation of this fold involves a diverse array of inter- and intramolecular structural features. These features include a long flexible loop connecting the two rungs, buried polar residues, salt bridges, and asparagine ladders. We have used site-directed mutagenesis and X-ray fiber diffraction to probe the relative importance of these features for the formation of β-solenoid structure, as well as the cumulative effects of multiple mutations. Using fibrillization kinetics and chemical stability assays, we have determined the biophysical effects of our mutations on the assembly and stability of the prion-forming domain. We have found that a diversity of structural features provides a level of redundancy that allows robust folding and stability even in the face of significant sequence alterations and suboptimal environmental conditions. Our findings provide fundamental insights into the structural interactions necessary for self-propagation. Propagation of prion structure seems to require an obligatory level of complexity that may not be reproducible in short peptide models.

  12. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

    Directory of Open Access Journals (Sweden)

    Patricia I Diaz

    2014-07-01

    Full Text Available High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  13. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

    Science.gov (United States)

    Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

    2014-01-01

    High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  14. Flexible Bayesian Human Fecundity Models.

    Science.gov (United States)

    Kim, Sungduk; Sundaram, Rajeshwari; Buck Louis, Germaine M; Pyper, Cecilia

    2012-12-01

    Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis.

  15. The Shigella human challenge model.

    Science.gov (United States)

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  16. Modeling of fungal and bacterial spore germination under static and dynamic conditions.

    Science.gov (United States)

    Peleg, Micha; Normand, Mark D

    2013-11-01

    Isothermal germination curves, sigmoid and nonsigmoid, can be described by a variety of models reminiscent of growth models. Two of these, which are consistent with the percent of germinated spores being initially zero, were selected: one, Weibullian (or "stretched exponential"), for more or less symmetric curves, and the other, introduced by Dantigny's group, for asymmetric curves (P. Dantigny, S. P.-M. Nanguy, D. Judet-Correia, and M. Bensoussan, Int. J. Food Microbiol. 146:176-181, 2011). These static models were converted into differential rate models to simulate dynamic germination patterns, which passed a test for consistency. In principle, these and similar models, if validated experimentally, could be used to predict dynamic germination from isothermal data. The procedures to generate both isothermal and dynamic germination curves have been automated and posted as freeware on the Internet in the form of interactive Wolfram demonstrations. A fully stochastic model of individual and small groups of spores, developed in parallel, shows that when the germination probability is constant from the start, the germination curve is nonsigmoid. It becomes sigmoid if the probability monotonically rises from zero. If the probability rate function rises and then falls, the germination reaches an asymptotic level determined by the peak's location and height. As the number of individual spores rises, the germination curve of their assemblies becomes smoother. It also becomes more deterministic and can be described by the empirical phenomenological models.

  17. A three-dimensional model of fungal morphogenesis based on the vesicle supply center concept.

    Science.gov (United States)

    Gierz, G; Bartnicki-Garcia, S

    2001-01-21

    We developed a three-dimensional model of hyphal morphogenesis under the same basic assumption used for the construction of a two-dimensional model. Namely, that the polarized growth of tubular cells (hyphoids) arises from a gradient of wall-building vesicles generated by a vesicle supply center (VSC). Contrary to the 2-D mathematical formulation, the three-dimensional derivation led to an indetermination whose solution required defining a priori the pattern of expansion of the wall, i.e. defining the overall spatial movement of the wall as the newly inserted wall elements displace the existing wall fabric. The patterns of wall expansion can be described by tracing the movement of marker points on the cell surface (point trajectories). Point trajectories were computed for three different modes of wall expansion of the VSC-generated hyphoids: orthogonal, isometric, and rotational. The 3-D VSC models allowed us to either stipulate or calculate the degree of anisotropy for each type of wall expansion. Wireframe models were built to visualize growth anisotropy in each model. Although the overall shape of the three hyphoid models is similar, they differ substantially in point trajectories and anisotropy. Point trajectories are experimentally testable and were the basis for the conclusion that hyphae grow in orthogonal fashion. (Bartnicki-Garcia et al., 2000. Biophys. J.79, 2382-2390.)

  18. Efficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogens

    Science.gov (United States)

    Zhao, Ge; Zaidi, Tanweer S.; Bozkurt-Guzel, Cagla; Zaidi, Tauqeer H.; Lederer, James A.; Priebe, Gregory P.; Pier, Gerald B.

    2016-01-01

    Purpose Developing immunotherapies for fungal eye infections is a high priority. We analyzed fungal pathogens for expression of the surface polysaccharide, poly-N-acetyl glucosamine (PNAG), and used a mouse model of ocular keratitis caused by Aspergillus flavus, A. fumigatus, or Fusarium solani to determine if PNAG was an immunotherapy target and requirements for ancillary cellular and molecular immune effectors. Methods Enzyme-linked immunosorbent assay (ELISA) or immunofluorescence was used to detect PNAG on fungal cells. Keratitis was induced by scratching corneas of C57BL/6, IL-17R KO, RAG-1 KO, or IL-22 KO mice followed by inoculation with fungal pathogens. Goat antibodies to PNAG, a PNAG-specific human IgG1 monoclonal antibody, or control antibodies were injected either prophylactically plus therapeutically or therapeutically only, and corneal pathology and fungal levels determined in infected eyes at 24 or 48 hours after infection. Results All tested fungal species produced PNAG. Prophylactic or therapeutic treatment by intraperitoneal (IP) injection of antibody to PNAG combined with post-infection topical application of antibody, the latter also used for A. fumigatus, led to reduced fungal levels, corneal pathology, and cytokine expression. Topical administration only of the PNAG monoclonal antibodies (MAb) reduced fungal loads and corneal pathology. There was no antibody protection in IL-17R KO, RAG-1 KO, or IL-22 KO mice. Conclusions Poly-N-acetyl glucosamine is produced by clinically important fungal ocular pathogens. Antibody to PNAG demonstrated protection against Aspergillus and Fusarium keratitis, requiring T cells producing IL-17 and IL-22. These findings indicate the potential to prevent or treat fungal infections by vaccines and immunotherapeutics to PNAG. PMID:28002842

  19. Serious fungal infections in Ecuador.

    Science.gov (United States)

    Zurita, J; Denning, D W; Paz-Y-Miño, A; Solís, M B; Arias, L M

    2017-06-01

    There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.

  20. Biocompatibility of potential wound management products: fungal mycelia as a source of chitin/chitosan and their effect on the proliferation of human F1000 fibroblasts in culture.

    Science.gov (United States)

    Chung, L Y; Schmidt, R J; Hamlyn, P F; Sagar, B F; Andrews, A M; Turner, T D

    1994-04-01

    Aspergillus oryzae, Mucor mucedo, and Phycomyces blakesleeanus cultures were examined as sources of chitin/chitosan. The nitrogen content of the alkali-treated mycelia/sporangiophores of A. oryzae, M. mucedo, and P. blakesleeanus was 2.52, 3.61, and 6.27% w/w, which relates to an estimated chitin content of 37, 52, and 91%, respectively. The effect of these fungal materials on the rate of proliferation of human F1000 fibroblasts in culture was examined. At 0.01% w/v, all three materials exhibited significant (P mucedo produced a significant (P mucedo, possessed cell attractant properties, again correlating with chitin content. If developed for use as wound management materials, the sporangiophores of P. blakesleeanus and the mycelium of M. mucedo could possibly promote the growth of fibroblasts and provide a matrix for their anchorage, thus contributing to the granulation phase of the healing cascade.

  1. Modulation of host-cell MAPkinase signaling during fungal infection

    OpenAIRE

    2015-01-01

    Fungal infections contribute substantially to human suffering and mortality. The interaction between fungal pathogens and their host involves the invasion and penetration of the surface epithelium, activation of cells of the innate immune system and the generation of an effective response to block infection. Numerous host-cell signaling pathways are activated during fungal infection. This review will focus on the main fungal pathogens Aspergillus fumigatus, Candida albicans and Cryptococcus n...

  2. Modeling of Human Joint Structures.

    Science.gov (United States)

    1982-09-01

    Radial Lateral " epicondyle Olecranon Radius Ulna Figure 3. Lateral aspect of the right elbow joint. -17- Annular Ligament This strong band encircles... elbow joint, knee joint, human joints, shoulder joint, ankle joint, joint models, hip joint, ligaments. 20. ABSTRACT (Continue on reverse side If...ligaments. -A rather extended discussion of the articulations and anatomical descriptions of the elbow , shoulder, hip, knee and ankle joints are

  3. Assessment of Ustilago maydis as a fungal model for root infection studies.

    Science.gov (United States)

    Mazaheri-Naeini, Mahta; Sabbagh, Seyed Kazem; Martinez, Yves; Séjalon-Delmas, Nathalie; Roux, Christophe

    2015-03-01

    Ustilago maydis is a fungus infecting aerial parts of maize to form smutted galls. Due to its interest as a genetic tool in plant pathology, we evaluated its ability to penetrate into plant roots. The fungus can penetrate between epidermic root cells, forming inter and intracellular pseudohyphae. Root infection didn't provoke gall formation on the maize lines tested, and targeted PCR detection showed that U. maydis, unlike the other maize smut fungus Sporisorium reilianum, has a weak aptitude to grow from the roots up to the aerial part of maize. We also observed that U. maydis can infect Medicago truncatula hairy roots as an alternative host. This plant species is a model host to study root symbiosis, and this pathosystem can provide new insights on root-microbe interactions. Considering that U. maydis could be a soil fungus, we tested its responsiveness to GR24, a strigolactone analogue. Strigolactones are root exuded molecules which activate mitochondrial metabolism of arbuscular mycorrhizal (AM) fungi. Physiologic and molecular analysis revealed that GR24 also increases cell respiration of U. maydis. This result points out that strigolactones could have an incidence on several rhizospheric microbes. These data provide evidences that the biotrophic pathogen U. maydis has to be considered for studying root infection.

  4. Entomopathogenic fungal endophytes

    Science.gov (United States)

    Fungal endophytes are quite common in nature and some of them have been shown to have adverse effects against insects, nematodes, and plant pathogens. An introduction to fungal endophytes will be presented, followed by a discussion of research aimed at introducing Beauveria bassiana as a fungal endo...

  5. Characteristics of bacterial and fungal growth in plastic bottled beverages under a consuming condition model.

    Science.gov (United States)

    Watanabe, Maiko; Ohnishi, Takahiro; Araki, Emiko; Kanda, Takashi; Tomita, Atsuko; Ozawa, Kazuhiro; Goto, Keiichi; Sugiyama, Kanji; Konuma, Hirotaka; Hara-Kudo, Yukiko

    2014-01-01

    Microbial contamination in unfinished beverages can occur when drinking directly from the bottle. Various microorganisms, including foodborne pathogens, are able to grow in these beverages at room temperature or in a refrigerator. In this study, we elucidated the characteristics of microorganism growth in bottled beverages under consuming condition models. Furthermore, we provide insight into the safety of partially consumed bottled beverages with respect to food hygiene. We inoculated microorganisms, including foodborne pathogens, into various plastic bottled beverages and analysed the dynamic growth of microorganisms as well as bacterial toxin production in the beverages. Eight bottled beverage types were tested in this study, namely green tea, apple juice drink, tomato juice, carbonated drink, sport drink, coffee with milk, isotonic water and mineral water, and in these beverages several microorganism types were used: nine bacteria including three toxin producers, three yeasts, and five moulds. Following inoculation, the bottles were incubated at 35°C for 48 h for bacteria, 25°C for 48 h for yeasts, and 25°C for 28 days for moulds. During the incubation period, the number of bacteria and yeasts and visible changes in mould-growth were determined over time. Our results indicated that combinations of the beverage types and microorganism species correlated with the degree of growth. Regarding factors that affect the growth and toxin-productivity of microorganisms in beverages, it is speculated that the pH, static/shaking culture, temperature, additives, or ingredients, such as carbon dioxide or organic matter (especially of plant origin), may be important for microorganism growth in beverages. Our results suggest that various types of unfinished beverages have microorganism growth and can include food borne pathogens and bacterial toxins. Therefore, our results indicate that in terms of food hygiene it is necessary to consume beverages immediately after opening

  6. Fungal artificial chromosomes for mining of the fungal secondary metabolome

    OpenAIRE

    2015-01-01

    Background With thousands of fungal genomes being sequenced, each genome containing up to 70 secondary metabolite (SM) clusters 30–80 kb in size, breakthrough techniques are needed to characterize this SM wealth. Results Here we describe a novel system-level methodology for unbiased cloning of intact large SM clusters from a single fungal genome for one-step transformation and expression in a model host. All 56 intact SM clusters from Aspergillus terreus were individually captured in self-rep...

  7. Filamentous fungal-specific septin AspE is phosphorylated in vivo and interacts with actin, tubulin and other septins in the human pathogen Aspergillus fumigatus

    Energy Technology Data Exchange (ETDEWEB)

    Juvvadi, Praveen Rao; Belina, Detti [Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC (United States); Soderblom, Erik J.; Moseley, M. Arthur [Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC (United States); Steinbach, William J., E-mail: bill.steinbach@duke.edu [Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC (United States); Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC (United States)

    2013-02-15

    Highlights: ► In vivo interactions of the novel septin AspE were identified by GFP-Trap® affinity purification. ► Septins AspA, AspB, AspC and AspD interacted with AspE in vivo. ► Actin and tubulin interacted with AspE in vivo. ► AspE is phosphorylated at six serine residues in vivo. -- Abstract: We previously analyzed the differential localization patterns of five septins (AspA–E), including a filamentous fungal-specific septin, AspE, in the human pathogen Aspergillus fumigatus. Here we utilized the A. fumigatus strain expressing an AspE–EGFP fusion protein and show that this novel septin with a tubular localization pattern in hyphae is phosphorylated in vivo and interacts with the other septins, AspA, AspB, AspC and AspD. The other major proteins interacting with AspE included the cytoskeletal proteins, actin and tubulin, which may be involved in the organization and transport of the septins. This is the first report analyzing the phosphorylation of AspE and localizing the sites of phosphorylation, and opens opportunities for further analysis on the role of post-translational modifications in the assembly and organization of A. fumigatus septins. This study also describes the previously unknown interaction of AspE with the actin-microtubule network. Furthermore, the novel GFP-Trap® affinity purification method used here complements widely-used GFP localization studies in fungal systems.

  8. Absence of Fungal Spore Internalization by Bronchial Epithelium in Mouse Models Evidenced by a New Bioimaging Approach and Transmission Electronic Microscopy.

    Science.gov (United States)

    Rammaert, Blandine; Jouvion, Grégory; de Chaumont, Fabrice; Garcia-Hermoso, Dea; Szczepaniak, Claire; Renaudat, Charlotte; Olivo-Marin, Jean-Christophe; Chrétien, Fabrice; Dromer, Françoise; Bretagne, Stéphane

    2015-09-01

    Clinical data and experimental studies suggest that bronchial epithelium could serve as a portal of entry for invasive fungal infections. We therefore analyzed the interactions between molds and the bronchial/bronchiolar epithelium at the early steps after inhalation. We developed invasive aspergillosis (Aspergillus fumigatus) and mucormycosis (Lichtheimia corymbifera) murine models that mimic the main clinical risk factors for these infections. Histopathology studies were completed with a specific computer-assisted morphometric method to quantify bronchial and alveolar spores and with transmission electron microscopy. Morphometric analysis revealed a higher number of bronchial/bronchiolar spores for A. fumigatus than L. corymbifera. The bronchial/bronchiolar spores decreased between 1 and 18 hours after inoculation for both fungi, except in corticosteroid-treated mice infected with A. fumigatus, suggesting an effect of cortisone on bronchial spore clearance. No increase in the number of spores of any species was observed over time at the basal pole of the epithelium, suggesting the lack of transepithelial crossing. Transmission electron microscopy did not show spore internalization by bronchial epithelial cells. Instead, spores were phagocytized by mononuclear cells on the apical pole of epithelial cells. Early epithelial internalization of fungal spores in vivo cannot explain the bronchial/bronchiolar epithelium invasion observed in some invasive mold infections. The bioimaging approach provides a useful means to accurately enumerate and localize the fungal spores in the pulmonary tissues.

  9. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    Science.gov (United States)

    Bue, Grant; Makinen, Janice; Cognata, Thomas

    2012-01-01

    Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

  10. Modeling Forces on the Human Body.

    Science.gov (United States)

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-01-01

    Presents five models of the human body as a mechanical system which can be used in introductory physics courses: human arms as levers, humans falling from small heights, a model of the human back, collisions during football, and the rotating gymnast. Gives ideas for discussions and activities, including Interactive Physics (TM) simulations. (WRM)

  11. The Fungal Defensin Family Enlarged

    Directory of Open Access Journals (Sweden)

    Jiajia Wu

    2014-08-01

    Full Text Available Fungi are an emerging source of peptide antibiotics. With the availability of a large number of model fungal genome sequences, we can expect that more and more fungal defensin-like peptides (fDLPs will be discovered by sequence similarity search. Here, we report a total of 69 new fDLPs encoded by 63 genes, in which a group of fDLPs derived from dermatophytes are defined as a new family (fDEF8 according to sequence and phylogenetic analyses. In the oleaginous fungus Mortierella alpine, fDLPs have undergone extensive gene expansion. Our work further enlarges the fungal defensin family and will help characterize new peptide antibiotics with therapeutic potential.

  12. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, Jun; Saunders, Charles W.; Hu, Ping; Grant, Raymond A.; Boekhout, Teun; Kuramae, Eiko E.; Kronstad, James W.; DeAngelis, Yvonne M.; Reeder, Nancy L.; Johnstone, Kevin R.; Leland, Meredith; Fieno, Angela M.; Begley, William M.; Sun, Yiping; Lacey, Martin P.; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect > 50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

  13. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, J.; Saunders, C.; Hu, P.; Grant, R.A.; Boekhout, T.; Kuramae, E.E.; Kronstad, J.W.; DeAngelis, Y.M.; Reeder, N.L.; Johnstone, K.R.; Leland, M.; Fieno, A.M.; Begley, W.M.; Sun, Y.; Lacey, M.P.; Chaudhary, T.; Keough, T.; Chu, L.; Sears, R.; Yuan, B.; Dawson Jr., T.L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

  14. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, Jun; Saunders, Charles W.; Hu, Ping; Grant, Raymond A.; Boekhout, Teun; Kuramae, Eiko E.; Kronstad, James W.; DeAngelis, Yvonne M.; Reeder, Nancy L.; Johnstone, Kevin R.; Leland, Meredith; Fieno, Angela M.; Begley, William M.; Sun, Yiping; Lacey, Martin P.; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect > 50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably lit

  15. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, J.; Saunders, C.; Hu, P.; Grant, R.A.; Boekhout, T.; Kuramae, E.E.; Kronstad, J.W.; DeAngelis, Y.M.; Reeder, N.L.; Johnstone, K.R.; Leland, M.; Fieno, A.M.; Begley, W.M.; Sun, Y.; Lacey, M.P.; Chaudhary, T.; Keough, T.; Chu, L.; Sears, R.; Yuan, B.; Dawson Jr., T.L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably litt

  16. Fungal colonization of air-conditioning systems

    Directory of Open Access Journals (Sweden)

    Ljaljević-Grbić Milica

    2008-01-01

    Full Text Available Fungi have been implicated as quantitatively the most important bioaerosol component of indoor air associated with contaminated air-conditioning systems. rarely, indoor fungi may cause human infections, but more commonly allergenic responses ranging from pneumonitis to asthma-like symptoms. From all air conditioner filters analyzed, 16 fungal taxa were isolated and identified. Aspergillus fumigatus causes more lethal infections worldwide than any other mold. Air-conditioning filters that adsorb moisture and volatile organics appear to provide suitable substrates for fungal colonization. It is important to stress that fungal colonization of air-conditioning systems should not be ignored, especially in hospital environments.

  17. Modelling the scaling properties of human mobility

    Science.gov (United States)

    Song, Chaoming; Koren, Tal; Wang, Pu; Barabási, Albert-László

    2010-10-01

    Individual human trajectories are characterized by fat-tailed distributions of jump sizes and waiting times, suggesting the relevance of continuous-time random-walk (CTRW) models for human mobility. However, human traces are barely random. Given the importance of human mobility, from epidemic modelling to traffic prediction and urban planning, we need quantitative models that can account for the statistical characteristics of individual human trajectories. Here we use empirical data on human mobility, captured by mobile-phone traces, to show that the predictions of the CTRW models are in systematic conflict with the empirical results. We introduce two principles that govern human trajectories, allowing us to build a statistically self-consistent microscopic model for individual human mobility. The model accounts for the empirically observed scaling laws, but also allows us to analytically predict most of the pertinent scaling exponents.

  18. Fungal infections of the oral mucosa

    OpenAIRE

    P Anitha Krishnan

    2012-01-01

    Fungal infections in humans occur as a result of defects in the immune system. An increasing emergence in oral Candidal and non-Candidal fungal infections is evident in the past decade owing to the rise in the immunodeficient and immunocompromised population globally. Oral Candidal infection usually involves a compromised host and the compromise may be local or systemic. Local compromising factors include decreased salivation, poor oral hygiene, wearing dentures among others while systemic fa...

  19. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory; Joe, Jeffrey Clark [Idaho National Laboratory; Mandelli, Diego [Idaho National Laboratory

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  20. Myco-fluidics: The fluid dynamics of fungal chimerism

    Science.gov (United States)

    Roper, Marcus; Hickey, Patrick; Dressaire, Emilie; Roch, Sebastien

    2012-11-01

    Chimeras-fantastical creatures formed as amalgams of many animals-have captured the human imagination since Ancient times. But they are also surprisingly common in Nature. The syncytial cells of filamentous fungi harbor large numbers of nuclei bathed in a single cytoplasm. As a fungus grows these nuclei become genetically diverse, either from mutation or from exchange of nuclei between different fungal individuals, a process that is known to increase the virulence of the fungus and its adaptability. By directly measuring nuclear movement in the model ascomycete fungus Neurospora crassa, we show that the fungus' tolerance for internal genetic diversity is enabled by hydrodynamic mixing of nuclei acting at all length scales within the fungal mycelium. Mathematical modeling and experiments in a mutant with altered mycelial morphology reveal some of the exquisite hydraulic engineering necessary to create these mixing flows from spatially coarse pressure gradients.

  1. Freshwater Fungal Infections

    Directory of Open Access Journals (Sweden)

    Dennis J. Baumgardner

    2017-01-01

    Full Text Available Fungal infections as a result of freshwater exposure or trauma are fortunately rare. Etiologic agents are varied, but commonly include filamentous fungi and Candida. This narrative review describes various sources of potential freshwater fungal exposure and the diseases that may result, including fungal keratitis, acute otitis externa and tinea pedis, as well as rare deep soft tissue or bone infections and pulmonary or central nervous system infections following traumatic freshwater exposure during natural disasters or near-drowning episodes. Fungal etiology should be suspected in appropriate scenarios when bacterial cultures or molecular tests are normal or when the infection worsens or fails to resolve with appropriate antibacterial therapy.

  2. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  3. Molecular Characterization, Structural Modeling, and Evaluation of Antimicrobial Activity of Basrai Thaumatin-Like Protein against Fungal Infection

    Directory of Open Access Journals (Sweden)

    Nusrat Yasmin

    2017-01-01

    Full Text Available A thaumatin-like protein gene from Basrai banana was cloned and expressed in Escherichia coli. Amplified gene product was cloned into pTZ57R/T vector and subcloned into expression vector pET22b(+ and resulting pET22b-basrai TLP construct was introduced into E. coli BL21. Maximum protein expression was obtained at 0.7 mM IPTG concentration after 6 hours at 37°C. Western blot analysis showed the presence of approximately 20 kDa protein in induced cells. Basrai antifungal TLP was tried as pharmacological agent against fungal disease. Independently Basrai antifungal protein and amphotericin B exhibited their antifungal activity against A. fumigatus; however combined effect of both agents maximized activity against the pathogen. Docking studies were performed to evaluate the antimicrobial potential of TLP against A. fumigatus by probing binding pattern of antifungal protein with plasma membrane ergosterol of targeted fungal strain. Ice crystallization primarily damages frozen food items; however addition of antifreeze proteins limits the growth of ice crystal in frozen foods. The potential of Basrai TLP protein, as an antifreezing agent, in controlling the ice crystal formation in frozen yogurt was also studied. The scope of this study ranges from cost effective production of pharmaceutics to antifreezing and food preserving agent as well as other real life applications.

  4. Fungal Mating Pheromones: Choreographing the Dating Game

    Science.gov (United States)

    Jones, Stephen K.; Bennett, Richard J.

    2011-01-01

    Pheromones are ubiquitous from bacteria to mammals - a testament to their importance in regulating inter-cellular communication. In fungal species, they play a critical role in choreographing interactions between mating partners during the program of sexual reproduction. Here, we describe how fungal pheromones are synthesized, their interactions with G protein-coupled receptors, and the signals propagated by this interaction, using Saccharomyces cerevisiae as a reference point. Divergence from this model system is compared amongst the ascomycetes and basidiomycetes, which reveals the wealth of information that has been gleaned from studying pheromone-driven processes across a wide spectrum of the fungal kingdom. PMID:21496492

  5. Fungal mating pheromones: choreographing the dating game.

    Science.gov (United States)

    Jones, Stephen K; Bennett, Richard J

    2011-07-01

    Pheromones are ubiquitous from bacteria to mammals - a testament to their importance in regulating inter-cellular communication. In fungal species, they play a critical role in choreographing interactions between mating partners during the program of sexual reproduction. Here, we describe how fungal pheromones are synthesized, their interactions with G protein-coupled receptors, and the signals propagated by this interaction, using Saccharomyces cerevisiae as a reference point. Divergence from this model system is compared amongst the ascomycetes and basidiomycetes, which reveals the wealth of information that has been gleaned from studying pheromone-driven processes across a wide spectrum of the fungal kingdom.

  6. NUTRIENT TRANSFER IN VESICULAR-ARBUSCULAR MYCORRHIZAS: A NEW MODEL BASED ON THE DISTRIBUTION OF ATPases ON FUNGAL AND PLANT MEMBRANES

    Directory of Open Access Journals (Sweden)

    S.E. SMITH

    1995-01-01

    Full Text Available In this paper we review the membrane transport processes that are involved in the transfer of mineral nutrients and organic carbon between the symbiotic partners in mycorrhizas. In particular, we reassess the prevailing hypothesis that transfer in vesicular-arbuscular (VA mycorrhizas occurs simultaneously and bidirectionally across the same interface and that arbuscules are the main sites of transfer. Using cytochemical techniques, we and our collaborators have reexamined the distribution of ATPases in the arbuscular and intercellular hyphal interfaces in VA mycorrhizas formed between roots ofAllium cepa (onion and the fungus Glomus intraradices. The results showed that H +-ATPases have different localisation on plant and fungal membranes in arbuscular and hyphal interfaces (Gianinazzi-Pearson et al. 1991. While some arbuscular interfaces had H+-ATPase activity on both fungal and plant membranes, in most cases the fungal membrane lacked this activity. In contrast, the plasma membranes of intercellular hyphae always had H + -ATPase and the adjacent root cells did not. This suggests that the different interfaces in a VA mycorrhiza may have different functions. We propose that passive loss of P from the arbuscules is associated with active uptake by the energised (ATPase-bearing plant membrane and that passive loss of carbohydrate from the root cells is followed by active uptake by the intercellular hyphae. If this model is correct, then variations in "mycorrhizal efficiency" (i.e. the extent to which mycorrhizal plants grow better than non-mycorrhizal controls might be determined by differences in the numbers of active arbuscules as a proportion of the total fungal biomass within the root. As a first step towards investigating this possibility, we have developed methods for measuring the surface areas of arbuscular and hyphal interfaces in different fungus-host combinations, Glomus spp./ Allium porrum (leek. We have also measured fluxes of P from

  7. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  8. A virtual infection model quantifies innate effector mechanisms and Candida albicans immune escape in human blood.

    Directory of Open Access Journals (Sweden)

    Kerstin Hünniger

    2014-02-01

    Full Text Available Candida albicans bloodstream infection is increasingly frequent and can result in disseminated candidiasis associated with high mortality rates. To analyze the innate immune response against C. albicans, fungal cells were added to human whole-blood samples. After inoculation, C. albicans started to filament and predominantly associate with neutrophils, whereas only a minority of fungal cells became attached to monocytes. While many parameters of host-pathogen interaction were accessible to direct experimental quantification in the whole-blood infection assay, others were not. To overcome these limitations, we generated a virtual infection model that allowed detailed and quantitative predictions on the dynamics of host-pathogen interaction. Experimental time-resolved data were simulated using a state-based modeling approach combined with the Monte Carlo method of simulated annealing to obtain quantitative predictions on a priori unknown transition rates and to identify the main axis of antifungal immunity. Results clearly demonstrated a predominant role of neutrophils, mediated by phagocytosis and intracellular killing as well as the release of antifungal effector molecules upon activation, resulting in extracellular fungicidal activity. Both mechanisms together account for almost [Formula: see text] of C. albicans killing, clearly proving that beside being present in larger numbers than other leukocytes, neutrophils functionally dominate the immune response against C. albicans in human blood. A fraction of C. albicans cells escaped phagocytosis and remained extracellular and viable for up to four hours. This immune escape was independent of filamentation and fungal activity and not linked to exhaustion or inactivation of innate immune cells. The occurrence of C. albicans cells being resistant against phagocytosis may account for the high proportion of dissemination in C. albicans bloodstream infection. Taken together, iterative experiment-model

  9. Banana peel culture as an indigenous medium for easy identification of late-sporulation human fungal pathogens

    Directory of Open Access Journals (Sweden)

    A J Kindo

    2016-01-01

    Full Text Available Aim: Fungi are increasing in incidence as human pathogens and newer and rarer species are continuously being encountered. Identifying these species from growth on regular culture media may be challenging due to the absence of typical features. An indigenous and cheap medium, similar to the natural substrate of these fungi, was standardised in our laboratory as an aid to species identification in a conventional laboratory setting. Materials and Methods: Ripe banana peel pieces, sterilised in an autoclave at 121°C temperature and 15 lbs pressure for 15 min promoted good growth of hyphae and pycnidia or acervuli in coelomycetes, flabelliform and medusoid fruiting bodies of basidiomycetes and fruit bodies such as cleistothecium in ascomycetes. The growth from the primary isolation medium was taken and inoculated onto the pieces of double-autoclaved ripe banana peel pieces in a sterile glass Petri dish with some moisture (sprinkles of sterile distilled water. A few sterile coverslips were placed randomly inside the Petri dish for the growing fungus to stick on to it. The plates were kept at room temperature and left undisturbed for 15–20 days. At a time, one coverslip was taken out and placed on a slide with lactophenol cotton blue and focused under the microscope to look for fruit bodies. Results: Lasiodiplodia theobromae, Macrophomina phaseolina, Nigrospora sphaerica, Chaetomium murorum, Nattrassia mangiferae and Schizophyllum commune were identified by characteristic features from growth on banana peel culture. Conclusions: Banana peel culture is a cheap and effective medium resembling the natural substrate of fungi and is useful for promoting characteristic reproductive structures that aid identification.

  10. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  11. The human fungal pathogen Cryptococcus neoformans escapes macrophages by a phagosome emptying mechanism that is inhibited by Arp2/3 complex-mediated actin polymerisation.

    Directory of Open Access Journals (Sweden)

    Simon A Johnston

    Full Text Available The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin 'flashes' occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.

  12. Galleria mellonella as a model host for human pathogens: recent studies and new perspectives.

    Science.gov (United States)

    Junqueira, Juliana Campos

    2012-10-01

    The number of studies using G. mellonella as a model host for human pathogens has increased significantly in the last few years. Important studies were published from different countries for evaluating the pathogenesis of bacterial and fungal infections and for exploring the host defenses against pathogens. Therefore, standardized conditions for the use of G. melonella larvae need to be established. Recent research showed that the deprivation of G. mellonella larvae of food during the experiment caused a reduction in immune responses and an increased susceptibility to infection, suggesting that incubating of larvae in the presence or absence of nutrition may affect the results and comparisons among different laboratories.

  13. Human pathogenic bacteria, fungi, and viruses in Drosophila: disease modeling, lessons, and shortcomings.

    Science.gov (United States)

    Panayidou, Stavria; Ioannidou, Eleni; Apidianakis, Yiorgos

    2014-02-15

    Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection.

  14. 3-D Human Modeling and Animation

    CERN Document Server

    Ratner, Peter

    2012-01-01

    3-D Human Modeling and Animation Third Edition All the tools and techniques you need to bring human figures to 3-D life Thanks to today's remarkable technology, artists can create and animate realistic, three-dimensional human figures that were not possible just a few years ago. This easy-to-follow book guides you through all the necessary steps to adapt your own artistic skill in figure drawing, painting, and sculpture to this exciting digital canvas. 3-D Human Modeling and Animation, Third Edition starts you off with simple modeling, then prepares you for more advanced techniques for crea

  15. Human hand modelling: kinematics, dynamics, applications

    NARCIS (Netherlands)

    Gustus, A.; Stillfried, G.; Visser, J.; Jörntell, H.; Van der Smagt, P.

    2012-01-01

    An overview of mathematical modelling of the human hand is given. We consider hand models from a specific background: rather than studying hands for surgical or similar goals, we target at providing a set of tools with which human grasping and manipulation capabilities can be studied, and hand funct

  16. Fungal arthritis and osteomyelitis.

    Science.gov (United States)

    Kohli, Rakhi; Hadley, Susan

    2005-12-01

    Fungal arthritis and osteomyelitis are uncommon diseases and generally present in an indolent fashion. The incidence of fungal bone and joint dis-ease is increasing with an increase in the prevalence of factors predisposing to invasive fungal disease, such as the use of central venous catheters, broad spectrum antibiotics, immunosuppression, and abdominal surgery. Definitive diagnosis relies on bone or synovial culture or biopsy. Successful management has traditionally consisted of amphotericin B in combination with surgical debridement. Given the rarity of this disease, treatment is not well defined, but reports of success with the use of azole antifungal agents, including itraconazole, fluconazole, voriconazole, and posaconazole, are promising.

  17. Divergent and Convergent Evolution of Fungal Pathogenicity.

    Science.gov (United States)

    Shang, Yanfang; Xiao, Guohua; Zheng, Peng; Cen, Kai; Zhan, Shuai; Wang, Chengshu

    2016-05-12

    Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen-host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus-animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation. © The Author 2016. Published by Oxford University Press on behalf of the Society for

  18. Hidden Markov Models for Human Genes

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1997-01-01

    We analyse the sequential structure of human genomic DNA by hidden Markov models. We apply models of widely different design: conventional left-right constructs and models with a built-in periodic architecture. The models are trained on segments of DNA sequences extracted such that they cover...

  19. Insect pathology and fungal entomopathogens

    Science.gov (United States)

    Fungi that occur inside asymptomatic plant tissues are known as fungal endophytes. Different genera of fungal entomopathogens have been reported as naturally occurring fungal endophytes, and it has been shown that it is possible to inoculate plants with fungal entomopathogens, making them endophytic...

  20. Live-cell imaging of the early stages of colony development in Fusarium oxysporum in vitro and ex vivo during infection of a human corneal model

    OpenAIRE

    Kurian, Smija Mariam

    2016-01-01

    ABSTRACTThe University of ManchesterName: Smija Mariam KurianDegree title: Doctor of PhilosophyResearch title: Live-cell imaging of the early stages of colony development in Fusarium oxysporum in vitro and ex vivo during infection of a human corneal modelDate: May 2016Abstract: Fusarium oxysporum is a major fungal plant pathogen and emerging human pathogen. It has been hypothesised that conidial anastomosis tube (CAT) fusion may facilitate horizontal gene/chromosome transfer that could result...

  1. JGI Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  2. Human Centered Hardware Modeling and Collaboration

    Science.gov (United States)

    Stambolian Damon; Lawrence, Brad; Stelges, Katrine; Henderson, Gena

    2013-01-01

    In order to collaborate engineering designs among NASA Centers and customers, to in clude hardware and human activities from multiple remote locations, live human-centered modeling and collaboration across several sites has been successfully facilitated by Kennedy Space Center. The focus of this paper includes innovative a pproaches to engineering design analyses and training, along with research being conducted to apply new technologies for tracking, immersing, and evaluating humans as well as rocket, vehic le, component, or faci lity hardware utilizing high resolution cameras, motion tracking, ergonomic analysis, biomedical monitoring, wor k instruction integration, head-mounted displays, and other innovative human-system integration modeling, simulation, and collaboration applications.

  3. Human Exposure Modeling - Databases to Support Exposure Modeling

    Science.gov (United States)

    Human exposure modeling relates pollutant concentrations in the larger environmental media to pollutant concentrations in the immediate exposure media. The models described here are available on other EPA websites.

  4. Neglected fungal zoonoses : hidden threats to man and animals

    NARCIS (Netherlands)

    Seyedmousavi, S; Guillot, J; Tolooe, A; Verweij, P E; de Hoog, G S

    2015-01-01

    Zoonotic fungi can be naturally transmitted between animals and humans, and in some cases cause significant public health problems. A number of mycoses associated with zoonotic transmission are among the group of the most common fungal diseases, worldwide. It is, however, notable that some fungal di

  5. Neglected fungal zoonoses: hidden threats to man and animals

    NARCIS (Netherlands)

    Seyedmousavi, S.; Guillot, J.; Tolooe, A.; Verweij, P.E.; Hoog, G.S. de

    2015-01-01

    Zoonotic fungi can be naturally transmitted between animals and humans, and in some cases cause significant public health problems. A number of mycoses associated with zoonotic transmission are among the group of the most common fungal diseases, worldwide. It is, however, notable that some fungal di

  6. [Pathogenesis of invasive fungal infections].

    Science.gov (United States)

    Garcia-Vidal, Carolina; Carratalà, Jordi

    2012-03-01

    Invasive fungal infections remain a life-threatening disease. The development of invasive fungal disease is dependent on multiple factors, such us colonization and efficient host immune response. We aimed to review the pathogenesis of invasive fungal infections, in particular, those caused by Candida and Aspergillus. For this we propose, to describe the fungal characteristics, to detail the host defence mechanisms against fungus and to analyse the host risk factors for invasive fungal infection.

  7. Human Operator Control Strategy Model.

    Science.gov (United States)

    1980-04-01

    fashion. HOPE reflects the two-store theory of memory current in the psycho- logical literature ( Atkinson & Shiffrin , 1968; Broadbent, 1971). Two...uncertainty. In P.M.A. Rabbit & S. Dornic (Eds.), Attention and performance V. New York: Academic Press, 1975. Atkinson , R. C., & Shiffrin , R. M. Human...48 2. The Perception Process ... ............... 50 3. The Command Memory and Command Selection Process

  8. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  9. Allergic Responses Induced by a Fungal Biopesticide Metarhizium anisopliae and House Dust Mite Are Compared in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Marsha D. W. Ward

    2011-01-01

    Full Text Available Biopesticides can be effective in controlling their target pest. However, research regarding allergenicity and asthma development is limited. We compared the ability of fungal biopesticide Metarhizium anisopliae (MACA and house dust mite (HDM extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration at doubling doses (2.5–80 g protein 4X over a four-week period. Three days after the last exposure, serum and bronchoalveolar lavage fluid (BALF were collected. The extracts' relative allergenicity was evaluated based on response robustness (lowest significant dose response compared to control (0 g. MACA induced a more robust serum total IgE response than HDM. However, in the antigen-specific IgE assay, a similar dose of both MACA and HDM was required to achieve the same response level. Our data suggest a threshold dose of MACA for allergy induction and that M. anisopliae may be similar to HDM in allergy induction potential.

  10. Human body modeling in injury biomechanics

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Horst, M.J. van der; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling is widely used for crash-safety research and design. However, most occupant models used in crash simulations are based on crash dummies and thereby inherit their apparent limitations. This paper describes a mathematical model of the real human body for impact loading. A combin

  11. Modeling human operator involvement in robotic systems

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1991-01-01

    A modeling approach is presented to describe complex manned robotic systems. The robotic system is modeled as a (highly) nonlinear, possibly time-varying dynamic system including any time delays in terms of optimal estimation, control and decision theory. The role of the human operator(s) is modeled

  12. Candida Infections: An Update on Host Immune Defenses and Anti-Fungal Drugs

    Directory of Open Access Journals (Sweden)

    Ning Gao

    2016-04-01

    Full Text Available Infections by fungal pathogens such as Candida albicans and non-albicans Candida species are becoming increasing prevalent in the human population. Such pathogens cause life-threatening diseases with high mortality, particularly in immunocompromised patients. Host defenses against fungal infections are provided by an exquisite interplay between innate and adaptive immune responses. However, effective anti-fungal agents for Candida infections are limited, and fungal drug resistance is a significant treatment challenge. In this review, we summarize the current understanding of host–fungal interactions, discuss the modes action of anti-fungal drugs, explore host defense mechanisms, and define the new challenges for treating Candida infections.

  13. Cognitive modelling of human temporal reasoning

    NARCIS (Netherlands)

    ter Meulen, AGB

    2003-01-01

    Modelling human reasoning characterizes the fundamental human cognitive capacity to describe our past experience and use it to form expectations as well as plan and direct our future actions. Natural language semantics analyzes dynamic forms of reasoning in which the real-time order determines the

  14. Fungal endocarditis: current challenges.

    Science.gov (United States)

    Tattevin, Pierre; Revest, Matthieu; Lefort, Agnès; Michelet, Christian; Lortholary, Olivier

    2014-10-01

    Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.

  15. Murine models of human wound healing.

    Science.gov (United States)

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  16. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque...

  17. Dendritic Cell-Based Vaccine Against Fungal Infection.

    Science.gov (United States)

    Ueno, Keigo; Urai, Makoto; Ohkouchi, Kayo; Miyazaki, Yoshitsugu; Kinjo, Yuki

    2016-01-01

    Several pathogenic fungi, including Cryptococcus gattii, Histoplasma capsulatum, Coccidioides immitis, and Penicillium marneffei, cause serious infectious diseases in immunocompetent humans. However, currently, prophylactic and therapeutic vaccines are not clinically used. In particular, C. gattii is an emerging pathogen and thus far protective immunity against this pathogen has not been well characterized. Experimental vaccines such as component and attenuated live vaccines have been used as tools to study protective immunity against fungal infection. Recently, we developed a dendritic cell (DC)-based vaccine to study protective immunity against pulmonary infection by highly virulent C. gattii strain R265 that was clinically isolated from bronchial washings of infected patients during the Vancouver Island outbreak. In this approach, bone marrow-derived DCs (BMDCs) are pulsed with heat-killed C. gattii and then transferred into mice prior to intratracheal infection. This DC vaccine significantly increases interleukin 17A (IL-17A)-, interferon gamma (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing T cells in the lungs and spleen and ameliorates the pathology, fungal burden, and mortality following C. gattii infection. This approach may result in the development of a new means of controlling lethal fungal infections. In this chapter, we describe the procedures of DC vaccine preparation and murine pulmonary infection model for analysis of immune response against C. gattii.

  18. The Human-Artifact Model

    DEFF Research Database (Denmark)

    Bødker, Susanne; Klokmose, Clemens Nylandsted

    2011-01-01

    Although devices of all shapes and sizes currently dominate the technological landscape, human–computer interaction (HCI) as a field is not yet theoretically equipped to match this reality. In this article we develop the human–artifact model, which has its roots in activity theoretical HCI....... By reinterpreting the activity theoretical foundation, we present a framework that helps addressing the analysis of individual interactive artifacts while embracing that they are part of a larger ecology of artifacts. We show how the human–artifact model helps structuring the understanding of an artifact's action......-possibilities in relation to the artifact ecology surrounding it. Essential to the model is that it provides four interconnected levels of analysis and addresses the possibilities and problems at these four levels. Artifacts and their use are constantly developing, and we address development in, and of, use. The framework...

  19. Finite element modeling of the human pelvis

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, B.

    1995-11-01

    A finite element model of the human pelvis was created using a commercial wire frame image as a template. To test the final mesh, the model`s mechanical behavior was analyzed through finite element analysis and the results were displayed graphically as stress concentrations. In the future, this grid of the pelvis will be integrated with a full leg model and used in side-impact car collision simulations.

  20. A complex small RNA repertoire is generated by a plant/fungal-like machinery and effected by a metazoan-like Argonaute in the single-cell human parasite Toxoplasma gondii.

    Science.gov (United States)

    Braun, Laurence; Cannella, Dominique; Ortet, Philippe; Barakat, Mohamed; Sautel, Céline F; Kieffer, Sylvie; Garin, Jérôme; Bastien, Olivier; Voinnet, Olivier; Hakimi, Mohamed-Ali

    2010-05-27

    In RNA silencing, small RNAs produced by the RNase-III Dicer guide Argonaute-like proteins as part of RNA-induced silencing complexes (RISC) to regulate gene expression transcriptionally or post-transcriptionally. Here, we have characterized the RNA silencing machinery and exhaustive small RNAome of Toxoplasma gondii, member of the Apicomplexa, a phylum of animal- and human-infecting parasites that cause extensive health and economic damages to human populations worldwide. Remarkably, the small RNA-generating machinery of Toxoplasma is phylogenetically and functionally related to that of plants and fungi, and accounts for an exceptionally diverse array of small RNAs. This array includes conspicuous populations of repeat-associated small interfering RNA (siRNA), which, as in plants, likely generate and maintain heterochromatin at DNA repeats and satellites. Toxoplasma small RNAs also include many microRNAs with clear metazoan-like features whose accumulation is sometimes extremely high and dynamic, an unexpected finding given that Toxoplasma is a unicellular protist. Both plant-like heterochromatic small RNAs and metazoan-like microRNAs bind to a single Argonaute protein, Tg-AGO. Toxoplasma miRNAs co-sediment with polyribosomes, and thus, are likely to act as translational regulators, consistent with the lack of catalytic residues in Tg-AGO. Mass spectrometric analyses of the Tg-AGO protein complex revealed a common set of virtually all known RISC components so far characterized in human and Drosophila, as well as novel proteins involved in RNA metabolism. In agreement with its loading with heterochromatic small RNAs, Tg-AGO also associates substoichiometrically with components of known chromatin-repressing complexes. Thus, a puzzling patchwork of silencing processor and effector proteins from plant, fungal and metazoan origin accounts for the production and action of an unsuspected variety of small RNAs in the single-cell parasite Toxoplasma and possibly in other

  1. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  2. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  3. Allergic Fungal Rhinosinusitis.

    Science.gov (United States)

    Hoyt, Alice E W; Borish, Larry; Gurrola, José; Payne, Spencer

    2016-01-01

    This article reviews the history of allergic fungal rhinosinusitis and the clinical, pathologic, and radiographic criteria necessary to establish its diagnosis and differentiate this disease from other types of chronic rhinosinusitis. Allergic fungal rhinosinusitis is a noninvasive fungal form of sinus inflammation characterized by an often times unilateral, expansile process in which the typical allergic "peanut-butter-like" mucin contributes to the formation of nasal polyps, hyposmia/anosmia, and structural changes of the face. IgE sensitization to fungi is a necessary, but not sufficient, pathophysiologic component of the disease process that is also defined by microscopic visualization of mucin-containing fungus and characteristic radiological imaging. This article expounds on these details and others including the key clinical and scientific distinctions of this diagnosis, the pathophysiologic mechanisms beyond IgE-mediated hypersensitivity that must be at play, and areas of current and future research.

  4. Immune response to fungal infections.

    Science.gov (United States)

    Blanco, Jose L; Garcia, Marta E

    2008-09-15

    The immune mechanisms of defence against fungal infections are numerous, and range from protective mechanisms that were present early in evolution (innate immunity) to sophisticated adaptive mechanisms that are induced specifically during infection and disease (adaptive immunity). The first-line innate mechanism is the presence of physical barriers in the form of skin and mucous membranes, which is complemented by cell membranes, cellular receptors and humoral factors. There has been a debate about the relative contribution of humoral and cellular immunity to host defence against fungal infections. For a long time it was considered that cell-mediated immunity (CMI) was important, but humoral immunity had little or no role. However, it is accepted now that CMI is the main mechanism of defence, but that certain types of antibody response are protective. In general, Th1-type CMI is required for clearance of a fungal infection, while Th2 immunity usually results in susceptibility to infection. Aspergillosis, which is a disease caused by the fungus Aspergillus, has been the subject of many studies, including details of the immune response. Attempts to relate aspergillosis to some form of immunosuppression in animals, as is the case with humans, have not been successful to date. The defence against Aspergillus is based on recognition of the pathogen, a rapidly deployed and highly effective innate effector phase, and a delayed but robust adaptive effector phase. Candida albicans, part of the normal microbial flora associated with mucous surfaces, can be present as congenital candidiasis or as acquired defects of cell-mediated immunity. Resistance to this yeast is associated with Th1 CMI, whereas Th2 immunity is associated with susceptibility to systemic infection. Dermatophytes produce skin alterations in humans and other animals, and the essential role of the CMI response is to destroy the fungi and produce an immunoprotective status against re-infection. The resolution

  5. Mathematical human modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    Mathematical modeling of the human body is widely used for automotive crash-safety research and design. Simulations have contributed to a reduction of injury numbers by optimization of vehicle structures and restraint systems. Currently, such simulations are largely performed using occupant models b

  6. Mathematical human modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    Mathematical modeling of the human body is widely used for automotive crash-safety research and design. Simulations have contributed to a reduction of injury numbers by optimization of vehicle structures and restraint systems. Currently, such simulations are largely performed using occupant models

  7. Mathematical human body modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling of the human body is widely used for automotive crash safety research and design. Simulations have contributed to a reduction of injury numbers by optimisation of vehicle structures and restraint systems. Currently such simulations are largely performed using occupant models

  8. Complex Systems and Human Performance Modeling

    Science.gov (United States)

    2013-12-01

    constitute a cognitive architecture or decomposing the work flows and resource constraints that characterize human-system interactions, the modeler...also explored the generation of so-called “ fractal ” series from simple task network models where task times are the calculated by way of a moving

  9. Models of the Human in Tantric Hinduism

    DEFF Research Database (Denmark)

    Olesen, Bjarne Wernicke; Flood, Gavin

    2018-01-01

    This research project explores the origins, developments and transformations of yogic models of the human (e.g. kundalini yoga, the cakra system and ritual sex) in the tantric goddess traditions or what might be called Śāktism of medieval India. These Śākta models of esoteric anatomy originating...

  10. Mathematical human body modelling for impact loading

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling of the human body is widely used for automotive crash safety research and design. Simulations have contributed to a reduction of injury numbers by optimisation of vehicle structures and restraint systems. Currently such simulations are largely performed using occupant models b

  11. Interior Design Research: A Human Ecosystem Model.

    Science.gov (United States)

    Guerin, Denise A.

    1992-01-01

    The interior ecosystems model illustrates effects on the human organism of the interaction of the natural, behavioral, and built environment. Examples of interior lighting and household energy consumption show the model's flexibility for organizing study variables in interior design research. (SK)

  12. A Model of the Human Eye

    Science.gov (United States)

    Colicchia, G.; Wiesner, H.; Waltner, C.; Zollman, D.

    2008-01-01

    We describe a model of the human eye that incorporates a variable converging lens. The model can be easily constructed by students with low-cost materials. It shows in a comprehensible way the functionality of the eye's optical system. Images of near and far objects can be focused. Also, the defects of near and farsighted eyes can be demonstrated.

  13. Interior Design Research: A Human Ecosystem Model.

    Science.gov (United States)

    Guerin, Denise A.

    1992-01-01

    The interior ecosystems model illustrates effects on the human organism of the interaction of the natural, behavioral, and built environment. Examples of interior lighting and household energy consumption show the model's flexibility for organizing study variables in interior design research. (SK)

  14. Establishment and pathological observation of rabbit model with fungal keratitis%兔眼真菌性角膜炎模型的病理学观察

    Institute of Scientific and Technical Information of China (English)

    董贤慧; 钱涛; 高维娟; 贺小平; 侯淑敏; 韦素春; 杨国兴

    2012-01-01

    目的 观察兔眼真菌性角膜炎(FK)动物模型的病理学改变.方法 新西兰白兔15只(30只眼),随机分为模型组、生理盐水组和正常对照组,每组10只兔眼.采用角膜基质注射法建立茄病镰刀菌性角膜炎模型,接种后2d角膜刮片行真菌培养;接种后1、2、6、8、l4、20 d和30 d,对兔眼溃疡评分;接种后3、8、15、30 d于裂隙灯下观察兔眼病理变化并拍照;接种后30 d处死家兔,取角膜,HE染色,光镜下观察组织病理学改变,PAS染色观察角膜基质层间的真菌菌丝,电镜观察角膜超微结构改变.结果 模型组角膜刮片真菌培养均可见典型真菌菌落生长;与正常对照组相比,模型组在接种1、2、6、8、14、20d和30 d后,角膜溃疡评分均有显著性差异(P<0.05).模型组接种3、8、15、30 d后,分别可见角膜溃疡、穿孔、前房积脓、新生血管、角膜白斑等并发症.HE染色、PAS染色、电镜观察均显示模型组角膜感染样改变.生理盐水组和正常对照组未见明显病理改变.结论 角膜基质注射法可以成功建立兔眼的真菌性角膜炎模型,出现典型的形态学改变.%Objective To observe the histopathological changes of animal models with fungal keratitis. Methods 15 New Zealand white rabbits (30 eyes) were divided into 3 groups, fungal keratitis model, saline and control groups. Fusarium Solani was injected into the corneal stroma of the eyes to establish fungal keratitis. Saline was injected into the corneal stroma of the eye8 of saline group. Noting was done in the control group. Lesion of cornea was taken and cultured after inoculated fungus for 2 days. The eyes of each group were examined clinically and respectively by slit lamp with a scoring system on day 1,2, 6, 8, 14, 20 and day 30. Photograph through the slit lamp on day 3, 8, 15 and day 30 after the inoculation. The rabbits were sacrificed with ear vein of air embolism at 30 day to observe the histological

  15. Human Muscle Fatigue Model in Dynamic Motions

    CERN Document Server

    Ma, Ruina; Bennis, Fouad; Ma, Liang

    2012-01-01

    Human muscle fatigue is considered to be one of the main reasons for Musculoskeletal Disorder (MSD). Recent models have been introduced to define muscle fatigue for static postures. However, the main drawbacks of these models are that the dynamic effect of the human and the external load are not taken into account. In this paper, each human joint is assumed to be controlled by two muscle groups to generate motions such as push/pull. The joint torques are computed using Lagrange's formulation to evaluate the dynamic factors of the muscle fatigue model. An experiment is defined to validate this assumption and the result for one person confirms its feasibility. The evaluation of this model can predict the fatigue and MSD risk in industry production quickly.

  16. ILC2s and fungal allergy

    Directory of Open Access Journals (Sweden)

    Hirohito Kita

    2015-07-01

    Full Text Available Innate lymphoid cells (ILCs have emerged recently as an important component of the immune system and the cell type that regulates mucosal immune responses and tissue homeostasis. Group 2 ILCs (ILC2s, a subset of ILCs, reside in various tissues and are characterized by their capacity to produce type 2 cytokines and tissue growth factors. These ILC2s play an important role in allergic immune responses by linking signals in the atmospheric environment to the immune system. Fungi are one of the major allergens associated with human asthma, and animal and in vitro models using the fungal allergens have provided significant information toward our understanding of the mechanisms of allergic disease. In mouse models of fungus-induced allergic airway inflammation, IL-33, IL-25, and TSLP are released by airway epithelial cells. Lung ILC2s that respond to these cytokines quickly produce a large quantity of type 2 cytokines, resulting in airway eosinophilia, mucus production, and airway hyperreactivity even in the absence of adaptive immune cells. Evidence also suggests that ILC2s interact with conventional immune cells, such as CD4+ T cells, and facilitate development of adaptive immune response and persistent airway inflammation. ILC2s are also present in respiratory mucosa in humans. Further investigations into the biology of ILC2s and their roles in the pathophysiology of allergic diseases will provide major conceptual advances in the field and may provide useful information toward development of new therapeutic strategies for patients.

  17. Mathematical models of human african trypanosomiasis epidemiology.

    Science.gov (United States)

    Rock, Kat S; Stone, Chris M; Hastings, Ian M; Keeling, Matt J; Torr, Steve J; Chitnis, Nakul

    2015-03-01

    Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT.

  18. Innate Defense against Fungal Pathogens.

    Science.gov (United States)

    Drummond, Rebecca A; Gaffen, Sarah L; Hise, Amy G; Brown, Gordon D

    2014-11-10

    Human fungal infections have been on the rise in recent years and proved increasingly difficult to treat as a result of the lack of diagnostics, effective antifungal therapies, and vaccines. Most pathogenic fungi do not cause disease unless there is a disturbance in immune homeostasis, which can be caused by modern medical interventions, disease-induced immunosuppression, and naturally occurring human mutations. The innate immune system is well equipped to recognize and destroy pathogenic fungi through specialized cells expressing a broad range of pattern recognition receptors (PRRs). This review will outline the cells and PRRs required for effective antifungal immunity, with a special focus on the major antifungal cytokine IL-17 and recently characterized antifungal inflammasomes.

  19. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  20. Mathematical modeling of the human knee joint

    Energy Technology Data Exchange (ETDEWEB)

    Ricafort, Juliet [Univ. of Southern California, Los Angeles, CA (United States). Dept. of Biomedical Engineering

    1996-05-01

    A model was developed to determine the forces exerted by several flexor and extensor muscles of the human knee under static conditions. The following muscles were studied: the gastrocnemius, biceps femoris, semitendinosus, semimembranosus, and the set of quadricep muscles. The tibia and fibula were each modeled as rigid bodies; muscles were modeled by their functional lines of action in space. Assumptions based on previous data were used to resolve the indeterminacy.

  1. Conceptual Data Modelling of Modern Human Migration

    Directory of Open Access Journals (Sweden)

    Kosta Sotiroski

    2012-12-01

    Full Text Available The processes of human migrations have been present for ages, since the very beginnings of human history on the planet Earth. Nowadays, these are amplified to a large scale due to the modern means of communication, transportation, information and knowledge exchange, as well as the complex processes of globalization. Knowing the social, demographic, ethnical and educational structure of the migrants, as well as their geographical trajectory and temporal dynamics of their spatial moving across territories, countries and continents, is of a crucial meaning for both national governments and international policies. There is an emphasized need for identifying, acquiring, organizing, storing, retrieving and analyzing data related to human migration processes. The relational databases provide an ultimate solution, whilst the E-R diagram represents a common graphical tool for conceptual data modelling and relational database design. Within the paper we develop and propose a logical data model of the modern human migration.

  2. Preclinical and human surrogate models of itch

    DEFF Research Database (Denmark)

    Hoeck, Emil August; Marker, Jens Broch; Gazerani, Parisa;

    2016-01-01

    Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch, are lim...... currently applied in animals and humans. This article is protected by copyright. All rights reserved.......Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine-resistant itch......, are limited. Relevant preclinical and human surrogate models of non-histaminergic itch are needed to accelerate the development of novel antipruritics and diagnostic tools. Advances in basic itch research have facilitated the development of diverse models of itch and associated dysesthesiae. While...

  3. Fungal Wound Infection

    Centers for Disease Control (CDC) Podcasts

    2016-01-28

    Dr. David Tribble, acting director of the infectious disease clinical research program at Uniformed Services University of the Health Sciences, discusses fungal wound infections after combat trauma.  Created: 1/28/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/28/2016.

  4. Fungal pathogens of Proteaceae

    NARCIS (Netherlands)

    Crous, P.W.; Summerell, B.A.; Swart, L.; Denman, S.; Taylor, J.E.; Bezuidenhout, C.M.; Palm, M.E.; Marincowitz, S.; Groenewald, J.Z.

    2011-01-01

    Species of Leucadendron, Leucospermum and Protea (Proteaceae) are in high demand for the international floriculture market due to their brightly coloured and textured flowers or bracts. Fungal pathogens, however, create a serious problem in cultivating flawless blooms. The aim of the present study

  5. Fungal pathogens of Proteaceae

    NARCIS (Netherlands)

    Crous, P.W.; Summerell, B.A.; Swart, L.; Denman, S.; Taylor, J.E.; Bezuidenhout, C.M.; Palm, M.E.; Marincowitz, S.; Groenewald, J.Z.

    2012-01-01

    Species of Leucadendron, Leucospermum and Protea (Proteaceae) are in high demand for the international floriculture market due to their brightly coloured and textured flowers or bracts. Fungal pathogens, however, create a serious problem in cultivating flawless blooms. The aim of the present study

  6. CGRP in human models of primary headaches

    DEFF Research Database (Denmark)

    Ashina, Håkan; Schytz, Henrik Winther; Ashina, Messoud

    2017-01-01

    experiments are likely due to assay variation; therefore, proper validation and standardization of an assay is needed. To what extent CGRP is involved in tension-type headache and cluster headache is unknown. CONCLUSION: Human models of primary headaches have elucidated the role of CGRP in headache......OBJECTIVE: To review the role of CGRP in human models of primary headaches and to discuss methodological aspects and future directions. DISCUSSION: Provocation experiments demonstrated a heterogeneous CGRP migraine response in migraine patients. Conflicting CGRP plasma results in the provocation...... pathophysiology and sparked great interest in developing new treatment strategies using CGRP antagonists and antibodies. Future studies applying more refined human experimental models should identify biomarkers of CGRP-induced primary headache and reveal whether CGRP provocation experiments could be used...

  7. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are ʹHuman Adaptive Mechatronics (HAMʹ and ʹHuman‐System Modelling (HSMʹ, are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operatorsʹ skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory‐motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human‐mechatronics systems are also mentioned.

  8. Animal and human models to understand ageing.

    Science.gov (United States)

    Lees, Hayley; Walters, Hannah; Cox, Lynne S

    2016-11-01

    Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

  9. A stochastic model of human gait dynamics

    Science.gov (United States)

    Ashkenazy, Yosef; M. Hausdorff, Jeffrey; Ch. Ivanov, Plamen; Eugene Stanley, H.

    2002-12-01

    We present a stochastic model of gait rhythm dynamics, based on transitions between different “neural centers”, that reproduces distinctive statistical properties of normal human walking. By tuning one model parameter, the transition (hopping) range, the model can describe alterations in gait dynamics from childhood to adulthood-including a decrease in the correlation and volatility exponents with maturation. The model also generates time series with multifractal spectra whose broadness depends only on this parameter. Moreover, we find that the volatility exponent increases monotonically as a function of the width of the multifractal spectrum, suggesting the possibility of a change in multifractality with maturation.

  10. Analisis Model Pengukuran Human Capital dalam Organisasi

    Directory of Open Access Journals (Sweden)

    Cecep Hidayat

    2013-11-01

    Full Text Available Measurement of human capital is not an easy to do because it is dynamic and always changing in accordance with the changing circumstances. Determination of dimensions and indicators of measurement needs to consider various factors such as situations and also the research scopes. This article has objectives to review the concepts, dimensions and measurement models of human capital. The research method used was literature study with a major reference source from current journal articles that discuss the measurement of human capital. Results of the study showed that basically the definition set forth in any dimension containing either explicitly or implicitly. In addition, the result indicated that there are three main categories of equality among researchers regarding the definition of human capital which emphasizes on: economic value/productivity, education, and abilities/competencies. The results also showed that the use of definitions, dimensions, and indicators for measurement of human capital depends on the situation, the scope of research, and the size of the organization. The conclusion of the study indicated that the measurement model and determination of dimensions and indicators of human capital measurement will determine the effectiveness of the measurement, and will have an impact on organizational performance.

  11. Engineering large animal models of human disease.

    Science.gov (United States)

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.

  12. Bayesian Modeling of a Human MMORPG Player

    CERN Document Server

    Synnaeve, Gabriel

    2010-01-01

    This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.

  13. Bayesian Modeling of a Human MMORPG Player

    Science.gov (United States)

    Synnaeve, Gabriel; Bessière, Pierre

    2011-03-01

    This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.

  14. Human ex vivo wound healing model.

    Science.gov (United States)

    Stojadinovic, Olivera; Tomic-Canic, Marjana

    2013-01-01

    Wound healing is a spatially and temporally regulated process that progresses through sequential, yet overlapping phases and aims to restore barrier breach. To study this complex process scientists use various in vivo and in vitro models. Here we provide step-by-step instructions on how to perform and employ an ex vivo wound healing model to assess epithelization during wound healing in human skin.

  15. Prospects for the development of fungal vaccines.

    Science.gov (United States)

    Deepe, G S

    1997-10-01

    In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require recognition and aggressive management. The escalation in the incidence and prevalence of infection has prompted a renewed interest in vaccine development. Herein, I discuss the most recent developments in the search for vaccines to combat fungal infections. Investigators have discovered several inert substances from various fungi that can mediate protection in animal models. The next challenge will be to find the suitable mode of delivery for these immunogens.

  16. Immunological Consequences of Intestinal Fungal Dysbiosis.

    Science.gov (United States)

    Wheeler, Matthew L; Limon, Jose J; Bar, Agnieszka S; Leal, Christian A; Gargus, Matthew; Tang, Jie; Brown, Jordan; Funari, Vincent A; Wang, Hanlin L; Crother, Timothy R; Arditi, Moshe; Underhill, David M; Iliev, Iliyan D

    2016-06-08

    Compared to bacteria, the role of fungi within the intestinal microbiota is poorly understood. In this study we investigated whether the presence of a "healthy" fungal community in the gut is important for modulating immune function. Prolonged oral treatment of mice with antifungal drugs resulted in increased disease severity in acute and chronic models of colitis, and also exacerbated the development of allergic airway disease. Microbiota profiling revealed restructuring of fungal and bacterial communities. Specifically, representation of Candida spp. was reduced, while Aspergillus, Wallemia, and Epicoccum spp. were increased. Oral supplementation with a mixture of three fungi found to expand during antifungal treatment (Aspergillus amstelodami, Epicoccum nigrum, and Wallemia sebi) was sufficient to recapitulate the exacerbating effects of antifungal drugs on allergic airway disease. Taken together, these results indicate that disruption of commensal fungal populations can influence local and peripheral immune responses and enhance relevant disease states.

  17. Modelling dengue epidemic spreading with human mobility

    Science.gov (United States)

    Barmak, D. H.; Dorso, C. O.; Otero, M.

    2016-04-01

    We explored the effect of human mobility on the spatio-temporal dynamics of Dengue with a stochastic model that takes into account the epidemiological dynamics of the infected mosquitoes and humans, with different mobility patterns of the human population. We observed that human mobility strongly affects the spread of infection by increasing the final size and by changing the morphology of the epidemic outbreaks. When the spreading of the disease is driven only by mosquito dispersal (flight), a main central focus expands diffusively. On the contrary, when human mobility is taken into account, multiple foci appear throughout the evolution of the outbreaks. These secondary foci generated throughout the outbreaks could be of little importance according to their mass or size compared with the largest main focus. However, the coalescence of these foci with the main one generates an effect, through which the latter develops a size greater than the one obtained in the case driven only by mosquito dispersal. This increase in growth rate due to human mobility and the coalescence of the foci are particularly relevant in temperate cities such as the city of Buenos Aires, since they give more possibilities to the outbreak to grow before the arrival of the low-temperature season. The findings of this work indicate that human mobility could be the main driving force in the dynamics of vector epidemics.

  18. AN EFFECTIVE HUMAN LEG MODELING METHOD

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Digital medicine is a new concept in medical field, and the need for digital human body is increasing these years. This paper used Free Form Deformation (FFD) to model the motion of human leg. It presented the motion equations of knee joint on the basis of anatomic structure and motion characters, then transmitted the deformation to the mesh of leg through a simplified FFD that only used two-order B-spline basis function. The experiments prove that this method can simulate the bend of leg and the deformation of muscles fairly well. Compared with the method of curved patches, this method is more convenient and effective. Further more, those equations can be easily applied to other joint models of human body.

  19. Modeling human craniofacial disorders in Xenopus.

    Science.gov (United States)

    Dubey, Aditi; Saint-Jeannet, Jean-Pierre

    2017-03-01

    Craniofacial disorders are among the most common human birth defects and present an enormous health care and social burden. The development of animal models has been instrumental to investigate fundamental questions in craniofacial biology and this knowledge is critical to understand the etiology and pathogenesis of these disorders. The vast majority of craniofacial disorders arise from abnormal development of the neural crest, a multipotent and migratory cell population. Therefore, defining the pathogenesis of these conditions starts with a deep understanding of the mechanisms that preside over neural crest formation and its role in craniofacial development. This review discusses several studies using Xenopus embryos to model human craniofacial conditions, and emphasizes the strength of this system to inform important biological processes as they relate to human craniofacial development and disease.

  20. Novel Taxa Associated with Human Fungal Black-Grain Mycetomas: Emarellia grisea gen. nov., sp. nov., and Emarellia paragrisea sp. nov.

    Science.gov (United States)

    Desnos-Ollivier, Marie; Campbell, Colin K.; Bridge, Paul D.; Dannaoui, Eric; Johnson, Elizabeth M.

    2016-01-01

    Eumycetoma is a debilitating, chronic, fungal infection that is endemic in India, Indonesia, and parts of Africa and South and Central America. It remains a neglected tropical disease in need of international recognition. Infections follow traumatic implantation of saprophytic fungi and frequently require radical surgery or amputation in the absence of appropriate treatment. Several fungal species can cause black-grain mycetomas, including Madurella spp. (Sordariales), Falciformispora spp., Trematosphaeria grisea, Biatriospora mackinnonii, Pseudochaetosphaeronema larense, and Medicopsis romeroi (all Pleosporales). We performed phylogenetic analyses based on five loci on 31 isolates from two international culture collections to establish the taxonomic affiliations of fungi that had been isolated from cases of black-grain mycetoma and historically classified as Madurella grisea. Although most strains were well resolved to species level and corresponded to known agents of eumycetoma, six independent isolates, which failed to produce conidia under any conditions tested, were only distantly related to existing members of the Pleosporales. Five of the six isolates shared >99% identity with each other and are described as Emarellia grisea gen. nov. and sp. nov; the sixth isolate represents a sister species in this novel genus and is described as Emarellia paragrisea. Several E. grisea isolates were present in both United Kingdom and French culture collections and had been isolated independently over 6 decades from cases of imported eumycetoma. Four of the six isolates involved patients that had originated on the Indian subcontinent. All isolates were all susceptible in vitro to the azole antifungals, but had elevated MICs with caspofungin. PMID:27076666

  1. An Outline Course on Human Performance Modeling

    Science.gov (United States)

    2006-01-01

    complementary or competing tasks: Dario SaIvucci, ??? 46. Bonnie Johns, David Kieras 47. ecological interface design 48. More into modeling human... alarcon 70. Ben Knott 71. Evelyn Rozanski 7.Pete Khooshabeh Optional: If ou would like to be on a mailin list for further seminars lease enter our email

  2. Modeling human muscle disease in zebrafish

    OpenAIRE

    Guyon, Jeffrey R.; Steffen, Leta S; Howell, Melanie H.; Pusack, Timothy J; Lawrence, Chris; Kunkel, Louis M

    2007-01-01

    Modeling human muscle disease in zebrafish correspondence: Corresponding author. Children's Hospital Boston, Enders Bldg, Rm 570, 300 Longwood Ave Boston, MA 02115. Tel.: +1 617 355 7576. (Kunkel, Louis M.) (Kunkel, Louis M.) Program in Genomics and Howard Hughes Medical Institute at Children's Hospital Boston - Boston--> , MA 02115--> - UNITED STATES (Guyon, Jeffrey R.) Program in Genomics a...

  3. Modeling and Simulating Virtual Anatomical Humans

    NARCIS (Netherlands)

    Madehkhaksar, Forough; Luo, Zhiping; Pronost, Nicolas; Egges, Arjan

    2014-01-01

    This chapter presents human musculoskeletal modeling and simulation as a challenging field that lies between biomechanics and computer animation. One of the main goals of computer animation research is to develop algorithms and systems that produce plausible motion. On the other hand, the main chall

  4. Future of human models for crash analysis

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    In the crash safety field mathematical models can be applied in practically all area's of research and development including: reconstruction of actual accidents, design (CAD) of the crash response of vehicles, safety devices and roadside facilities and in support of human impact biomechanical

  5. Future of human models for crash analysis

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Hoof, J.F.A.M. van; Lange, R. de

    2001-01-01

    In the crash safety field mathematical models can be applied in practically all area's of research and development including: reconstruction of actual accidents, design (CAD) of the crash response of vehicles, safety devices and roadside facilities and in support of human impact biomechanical studie

  6. Invasion of the Central Nervous System by Cryptococcus neoformans Requires a Secreted Fungal Metalloprotease

    Science.gov (United States)

    Vu, Kiem; Tham, Rick; Uhrig, John P.; Thompson, George R.; Na Pombejra, Sarisa; Jamklang, Mantana; Bautos, Jennifer M.

    2014-01-01

    ABSTRACT Cryptococcus spp. cause life-threatening fungal infection of the central nervous system (CNS), predominantly in patients with a compromised immune system. Why Cryptococcus neoformans has this remarkable tropism for the CNS is not clear. Recent research on cerebral pathogenesis of C. neoformans revealed a predominantly transcellular migration of cryptococci across the brain endothelium; however, the identities of key fungal virulence factors that function specifically to invade the CNS remain unresolved. Here we found that a novel, secreted metalloprotease (Mpr1) that we identified in the extracellular proteome of C. neoformans (CnMpr1) is required for establishing fungal disease in the CNS. Mpr1 belongs to a poorly characterized M36 class of fungalysins that are expressed in only some fungal species. A strain of C. neoformans lacking the gene encoding Mpr1 (mpr1Δ) failed to breach the endothelium in an in vitro model of the human blood-brain barrier (BBB). A mammalian host infected with the mpr1Δ null strain demonstrated significant improvement in survival due to a reduced brain fungal burden and lacked the brain pathology commonly associated with cryptococcal disease. The in vivo studies further indicate that Mpr1 is not required for fungal dissemination and Mpr1 likely targets the brain endothelium specifically. Remarkably, the sole expression of CnMPR1 in Saccharomyces cerevisiae resulted in a robust migration of yeast cells across the brain endothelium, demonstrating Mpr1’s specific activity in breaching the BBB and suggesting that Mpr1 may function independently of the hyaluronic acid-CD44 pathway. This distinct role for Mpr1 may develop into innovative treatment options and facilitate a brain-specific drug delivery platform. PMID:24895304

  7. Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

    Directory of Open Access Journals (Sweden)

    Cecilia Li

    2016-09-01

    Full Text Available Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK, which are involved in synthesizing inositol polyphosphates (IP. We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P and pyrophosphate (PP groups covalently attached at different positions. This review focuses on (1 the characterization of the Plc1/IPK pathway in C. neoformans; (2 the identification of PP-IP5 (IP7 as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3 why IPK enzymes represent suitable candidates for drug development.

  8. Virulence of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis in reconstituted human tissue models.

    Science.gov (United States)

    Gácser, Attila; Schäfer, Wilhelm; Nosanchuk, Jerome S; Salomon, Siegfried; Nosanchuk, Joshua D

    2007-12-01

    Candida parapsilosis is an increasingly important human pathogen. To study the interactions of C. parapsilosis with human tissues, we evaluated the effects of the CBS 604 type strain and three different clinical isolates on reconstituted human oral epithelial and epidermal tissues. The newly described species Candida orthopsilosis and Candida metapsilosis were also examined in these models. Microscopy of reconstituted tissues infected with yeast cells revealed severe attenuation, morphological changes and cellular damage. C. orthopsilosis caused damage similar to C. parapsilosis isolates, whereas C. metapsilosis was less virulent. To further quantitate tissue damage, we measured lactate dehydrogenase (LDH) in the culture supernatant. The relative LDH measurements correlated with our histopathological observations. We also examined the effect of the lipase inhibitor Ebelactone B and proteinase inhibitor Pepstatin A, to establish the utility of this model for studying factors of C. parapsilosis virulence. Both Ebelactone B and Pepstatin A reduced the destruction of epidermal and epithelial tissues. Our data show that reconstituted human tissues are extremely useful for modeling host interactions with C. parapsilosis and for studying fungal virulence factors.

  9. [Clinically documented fungal infections].

    Science.gov (United States)

    Kakeya, Hiroshi; Kohno, Shigeru

    2008-12-01

    Proven fungal infections are diagnosed by histological/microbiological evidence of fungi at the site of infection and positive blood culture (fungemia). However, invasive diagnosing examinations are not always applied for all of immunocompromised patients. Clinically documented invasive fungal infections are diagnosed by typical radiological findings such as halo sign on chest CT plus positive serological/molecular evidence of fungi. Serological tests of Aspergillus galactomannan antigen and beta-glucan for aspergillosis and cryptococcal glucuronoxylomannan antigen for cryptococcosis are useful. Hence, none of reliable serological tests for zygomycosis are available so far. In this article, risk factors, sign and symptoms, and diagnostic methods for clinically documented cases of invasive aspergillosis, pulmonary cryptococcosis, and zygomycosis with diabates, are reviewed.

  10. Constructing predictive models of human running.

    Science.gov (United States)

    Maus, Horst-Moritz; Revzen, Shai; Guckenheimer, John; Ludwig, Christian; Reger, Johann; Seyfarth, Andre

    2015-02-06

    Running is an essential mode of human locomotion, during which ballistic aerial phases alternate with phases when a single foot contacts the ground. The spring-loaded inverted pendulum (SLIP) provides a starting point for modelling running, and generates ground reaction forces that resemble those of the centre of mass (CoM) of a human runner. Here, we show that while SLIP reproduces within-step kinematics of the CoM in three dimensions, it fails to reproduce stability and predict future motions. We construct SLIP control models using data-driven Floquet analysis, and show how these models may be used to obtain predictive models of human running with six additional states comprising the position and velocity of the swing-leg ankle. Our methods are general, and may be applied to any rhythmic physical system. We provide an approach for identifying an event-driven linear controller that approximates an observed stabilization strategy, and for producing a reduced-state model which closely recovers the observed dynamics. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  11. Model of human visual-motion sensing

    Science.gov (United States)

    Watson, A. B.; Ahumada, A. J., Jr.

    1985-01-01

    A model of how humans sense the velocity of moving images is proposed. The model exploits constraints provided by human psychophysics, notably that motion-sensing elements appear tuned for two-dimensional spatial frequency, and by the frequency spectrum of a moving image, namely, that its support lies in the plane in which the temporal frequency equals the dot product of the spatial frequency and the image velocity. The first stage of the model is a set of spatial-frequency-tuned, direction-selective linear sensors. The temporal frequency of the response of each sensor is shown to encode the component of the image velocity in the sensor direction. At the second stage, these components are resolved in order to measure the velocity of image motion at each of a number of spatial locations and spatial frequencies. The model has been applied to several illustrative examples, including apparent motion, coherent gratings, and natural image sequences. The model agrees qualitatively with human perception.

  12. Space Station crew safety - Human factors model

    Science.gov (United States)

    Cohen, M. M.; Junge, M. K.

    1984-01-01

    A model of the various human factors issues and interactions that might affect crew safety is developed. The first step addressed systematically the central question: How is this Space Station different from all other spacecraft? A wide range of possible issue was identified and researched. Five major topics of human factors issues that interacted with crew safety resulted: Protocols, Critical Habitability, Work Related Issues, Crew Incapacitation and Personal Choice. Second, an interaction model was developed that would show some degree of cause and effect between objective environmental or operational conditions and the creation of potential safety hazards. The intermediary steps between these two extremes of causality were the effects on human performance and the results of degraded performance. The model contains three milestones: stressor, human performance (degraded) and safety hazard threshold. Between these milestones are two countermeasure intervention points. The first opportunity for intervention is the countermeasure against stress. If this countermeasure fails, performance degrades. The second opportunity for intervention is the countermeasure against error. If this second countermeasure fails, the threshold of a potential safety hazard may be crossed.

  13. Mathematical model with spatially uniform regulation explains long-range bidirectional transport of early endosomes in fungal hyphae.

    Science.gov (United States)

    Gou, Jia; Edelstein-Keshet, Leah; Allard, Jun

    2014-08-15

    In many cellular contexts, cargo is transported bidirectionally along microtubule bundles by dynein and kinesin-family motors. Upstream factors influence how individual cargoes are locally regulated, as well as how long-range transport is regulated at the whole-cell scale. Although the details of local, single-cargo bidirectional switching have been extensively studied, it remains to be elucidated how this results in cell-scale spatial organization. Here we develop a mathematical model of early endosome transport in Ustilago maydis. We demonstrate that spatiotemporally uniform regulation, with constant transition rates, results in cargo dynamics that is consistent with experimental data, including data from motor mutants. We find that microtubule arrays can be symmetric in plus-end distribution but asymmetric in binding-site distribution in a manner that affects cargo dynamics and that cargo can travel past microtubule ends in microtubule bundles. Our model makes several testable predictions, including secondary features of dynein and cargo distributions.

  14. Development of a realistic human airway model.

    Science.gov (United States)

    Lizal, Frantisek; Elcner, Jakub; Hopke, Philip K; Jedelsky, Jan; Jicha, Miroslav

    2012-03-01

    Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.

  15. Model of the Human Sleep Wake System

    CERN Document Server

    Rogers, Lisa

    2012-01-01

    A model and analysis of the human sleep/wake system is presented. The model is derived using the known neuronal groups, and their various projections, involved with sleep and wake. Inherent in the derivation is the existence of a slow time scale associated with homeostatic regulation, and a faster time scale associated with the dynamics within the sleep phase. A significant feature of the model is that it does not contain a periodic forcing term, common in other models, reflecting the fact that sleep/wake is not dependent upon a diurnal stimulus. Once derived, the model is analyzed using a linearized stability analysis. We then use experimental data from normal sleep-wake systems and orexin knockout systems to verify the physiological validity of the equations.

  16. Fungal infections of the oral mucosa.

    Science.gov (United States)

    Krishnan, P Anitha

    2012-01-01

    Fungal infections in humans occur as a result of defects in the immune system. An increasing emergence in oral Candidal and non-Candidal fungal infections is evident in the past decade owing to the rise in the immunodeficient and immunocompromised population globally. Oral Candidal infection usually involves a compromised host and the compromise may be local or systemic. Local compromising factors include decreased salivation, poor oral hygiene, wearing dentures among others while systemic factors include diabetes mellitus, nutritional deficiency, HIV infection/AIDS and others. Oral candidiasis is generally a localized infection and rarely appears as a systemic fungal disease whereas oral non-Candidal fungal infections are usually signs of disseminated disease. Some of the non-Candidal fungi that were once considered exotic and geographically restricted are now seen worldwide, beyond their natural habitat, probably attributed to globalization and travels. Currently infections from these fungi are more prevalent than before and they may present either as primary oral lesions or as oral manifestations of systemic mycoses. This review discusses the various predisposing factors, clinical presentations, clinical differential diagnosis, diagnosis and management of oral candidiasis, as well as briefly highlights upon a few of the more exotic non-Candidal fungi that infect the oral mucosa.

  17. From Glacier to Sauna: RNA-Seq of the Human Pathogen Black Fungus Exophiala dermatitidis under Varying Temperature Conditions Exhibits Common and Novel Fungal Response.

    Directory of Open Access Journals (Sweden)

    Barbara Blasi

    Full Text Available Exophiala dermatitidis (Wangiella dermatitidis belongs to the group of the so-called black yeasts. Thanks in part to its thick and strongly melanized cell walls, E. dermatitidis is extremely tolerant to various kinds of stress, including extreme pH, temperature and desiccation. E. dermatitidis is also the agent responsible for various severe illnesses in humans, such as pneumonia and keratitis, and might lead to fatal brain infections. Due to its association with the human environment, its poly-extremophilic lifestyle and its pathogenicity in humans, E. dermatitidis has become an important model organism. In this study we present the functional analysis of the transcriptional response of the fungus at 1°C and 45°C, in comparison with that at 37°C, for two different exposition times, i.e. 1 hour and 1 week. At 1°C, E. dermatitidis uses a large repertoire of tools to acclimatize, such as lipid membrane fluidization, trehalose production or cytoskeleton rearrangement, which allows the fungus to remain metabolically active. At 45°C, the fungus drifts into a replicative state and increases the activity of the Golgi apparatus. As a novel finding, our study provides evidence that, apart from the protein coding genes, non-coding RNAs, circular RNAs as well as fusion-transcripts are differentially regulated and that the function of the fusion-transcripts can be related to the corresponding temperature condition. This work establishes that E. dermatitidis adapts to its environment by modulating coding and non-coding gene transcription levels and through the regulation of chimeric and circular RNAs.

  18. From Glacier to Sauna: RNA-Seq of the Human Pathogen Black Fungus Exophiala dermatitidis under Varying Temperature Conditions Exhibits Common and Novel Fungal Response.

    Science.gov (United States)

    Blasi, Barbara; Tafer, Hakim; Tesei, Donatella; Sterflinger, Katja

    2015-01-01

    Exophiala dermatitidis (Wangiella dermatitidis) belongs to the group of the so-called black yeasts. Thanks in part to its thick and strongly melanized cell walls, E. dermatitidis is extremely tolerant to various kinds of stress, including extreme pH, temperature and desiccation. E. dermatitidis is also the agent responsible for various severe illnesses in humans, such as pneumonia and keratitis, and might lead to fatal brain infections. Due to its association with the human environment, its poly-extremophilic lifestyle and its pathogenicity in humans, E. dermatitidis has become an important model organism. In this study we present the functional analysis of the transcriptional response of the fungus at 1°C and 45°C, in comparison with that at 37°C, for two different exposition times, i.e. 1 hour and 1 week. At 1°C, E. dermatitidis uses a large repertoire of tools to acclimatize, such as lipid membrane fluidization, trehalose production or cytoskeleton rearrangement, which allows the fungus to remain metabolically active. At 45°C, the fungus drifts into a replicative state and increases the activity of the Golgi apparatus. As a novel finding, our study provides evidence that, apart from the protein coding genes, non-coding RNAs, circular RNAs as well as fusion-transcripts are differentially regulated and that the function of the fusion-transcripts can be related to the corresponding temperature condition. This work establishes that E. dermatitidis adapts to its environment by modulating coding and non-coding gene transcription levels and through the regulation of chimeric and circular RNAs.

  19. The role of the cell wall in fungal pathogenesis.

    Science.gov (United States)

    Arana, David M; Prieto, Daniel; Román, Elvira; Nombela, César; Alonso-Monge, Rebeca; Pla, Jesús

    2009-05-01

    Fungal infections are a serious health problem. In recent years, basic research is focusing on the identification of fungal virulence factors as promising targets for the development of novel antifungals. The wall, as the most external cellular component, plays a crucial role in the interaction with host cells mediating processes such as adhesion or phagocytosis that are essential during infection. Specific components of the cell wall (called PAMPs) interact with specific receptors in the immune cell (called PRRs), triggering responses whose molecular mechanisms are being elucidated. We review here the main structural carbohydrate components of the fungal wall (glucan, mannan and chitin), how their biogenesis takes place in fungi and the specific receptors that they interact with. Different model fungal pathogens are chosen to illustrate the functional consequences of this interaction. Finally, the identification of the key components will have important consequences in the future and will allow better approaches to treat fungal infections.

  20. Potential for Combined Biocontrol Activity against Fungal Fish and Plant Pathogens by Bacterial Isolates from a Model Aquaponic System

    Directory of Open Access Journals (Sweden)

    Ivaylo Sirakov

    2016-11-01

    Full Text Available One of the main challenges in aquaponics is disease control. One possible solution for this is biological control with organisms exerting inhibitory effects on fish and plant pathogens. The aim of this study was to examine the potential of isolating microorganisms that exert an inhibitory effect on both plant and fish pathogens from an established aquaponic system. We obtained 924 isolates on selective King’s B agar and 101 isolates on MRS agar from different compartments of a model aquaponic system and tested them for antagonism against the plant pathogen Pythium ultimum and fish pathogen Saprolegnia parasitica. Overall, 42 isolates were able to inhibit both fungi. Although not yet tested in vivo, these findings open new options for the implementation of biological control of diseases in aquaponics, where plants and fish are cultivated in the same water recirculating system.

  1. Computer Modeling of Human Delta Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Tatyana Dzimbova

    2013-04-01

    Full Text Available The development of selective agonists of δ-opioid receptor as well as the model of interaction of ligands with this receptor is the subjects of increased interest. In the absence of crystal structures of opioid receptors, 3D homology models with different templates have been reported in the literature. The problem is that these models are not available for widespread use. The aims of our study are: (1 to choose within recently published crystallographic structures templates for homology modeling of the human δ-opioid receptor (DOR; (2 to evaluate the models with different computational tools; and (3 to precise the most reliable model basing on correlation between docking data and in vitro bioassay results. The enkephalin analogues, as ligands used in this study, were previously synthesized by our group and their biological activity was evaluated. Several models of DOR were generated using different templates. All these models were evaluated by PROCHECK and MolProbity and relationship between docking data and in vitro results was determined. The best correlations received for the tested models of DOR were found between efficacy (erel of the compounds, calculated from in vitro experiments and Fitness scoring function from docking studies. New model of DOR was generated and evaluated by different approaches. This model has good GA341 value (0.99 from MODELLER, good values from PROCHECK (92.6% of most favored regions and MolProbity (99.5% of favored regions. Scoring function correlates (Pearson r = -0.7368, p-value = 0.0097 with erel of a series of enkephalin analogues, calculated from in vitro experiments. So, this investigation allows suggesting a reliable model of DOR. Newly generated model of DOR receptor could be used further for in silico experiments and it will give possibility for faster and more correct design of selective and effective ligands for δ-opioid receptor.

  2. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  3. Cunninghamella echinulata causing fatally invasive fungal sinusitis.

    Science.gov (United States)

    LeBlanc, Robert E; Meriden, Zina; Sutton, Deanna A; Thompson, Elizabeth H; Neofytos, Dionissios; Zhang, Sean X

    2013-08-01

    We report a fatal case of invasive fungal sinusitis caused by Cunninghamella echinulata in a febrile, neutropenic 15-year-old male with relapsing acute leukemia. The isolate was recovered from a nasal biopsy from the right middle meatus, and microscopic examination of the tissue revealed angioinvasion and necrosis. Human infection caused by this organism has not been well documented; however, this report alerts us to its life-threatening potential.

  4. De novo assembly of a 40 Mb eukaryotic genome from short sequence reads: Sordaria macrospora, a model organism for fungal morphogenesis.

    Science.gov (United States)

    Nowrousian, Minou; Stajich, Jason E; Chu, Meiling; Engh, Ines; Espagne, Eric; Halliday, Karen; Kamerewerd, Jens; Kempken, Frank; Knab, Birgit; Kuo, Hsiao-Che; Osiewacz, Heinz D; Pöggeler, Stefanie; Read, Nick D; Seiler, Stephan; Smith, Kristina M; Zickler, Denise; Kück, Ulrich; Freitag, Michael

    2010-04-08

    Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30-90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in approximately 4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb) with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data can be used for

  5. Human Factors Engineering Program Review Model

    Science.gov (United States)

    2004-02-01

    AA NUREG -0711,Rev. 2 Human Factors Engineering Program Review Model 20081009191 I i m To] Bi U.S. Nuclear Regulatory Commission Office of...Material As of November 1999, you may electronically access NUREG -series publications and other NRC records at NRC’s Public Electronic Reading Room at...http://www.nrc.qov/readinq-rm.html. Publicly released records include, to name a few, NUREG -series publications; Federal Register notices; applicant

  6. Human Plague Risk: Spatial-Temporal Models

    Science.gov (United States)

    Pinzon, Jorge E.

    2010-01-01

    This chpater reviews the use of spatial-temporal models in identifying potential risks of plague outbreaks into the human population. Using earth observations by satellites remote sensing there has been a systematic analysis and mapping of the close coupling between the vectors of the disease and climate variability. The overall result is that incidence of plague is correlated to positive El Nino/Southem Oscillation (ENSO).

  7. CCR7 deficiency on dendritic cells enhances fungal clearance in a murine model of pulmonary invasive aspergillosis.

    Science.gov (United States)

    Hartigan, Adam J; Westwick, John; Jarai, Gabor; Hogaboam, Cory M

    2009-10-15

    Aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment and is easily cleared from immunocompetent hosts. Invasive aspergillosis develops in immunocompromised patients, and is a leading cause of mortality in hematopoietic stem cell transplant recipients. CCR7 and its ligands, CCL19 and CCL21, are responsible for the migration of dendritic cells from sites of infection and inflammation to secondary lymphoid organs. To investigate the role of CCR7 during invasive aspergillosis, we used a well-characterized neutropenic murine model. During invasive aspergillosis, mice with a CCR7 deficiency in the hematopoietic compartment exhibited increased survival and less pulmonary injury compared with the appropriate wild-type control. Flow cytometric analysis of the chimeric mice revealed an increase in the number of dendritic cells present in the lungs of CCR7-deficient chimeras following infection with Aspergillus conidia. An adoptive transfer of dendritic cells into neutropenic mice provided a protective effect during invasive aspergillosis, which was further enhanced with the adoptive transfer of CCR7-deficient dendritic cells. Additionally, CCR7-deficient dendritic cells activated in vitro with Aspergillus conidia expressed higher TNF-alpha, CXCL10, and CXCL2 levels, indicating a more activated cellular response to the fungus. Our results suggest that the absence of CCR7 is protective during invasive aspergillosis in neutropenic mice. Collectively, these data demonstrate a potential deleterious role for CCR7 during primary immune responses directed against A. fumigatus.

  8. MODELING HUMAN RELIABILITY ANALYSIS USING MIDAS

    Energy Technology Data Exchange (ETDEWEB)

    Ronald L. Boring; Donald D. Dudenhoeffer; Bruce P. Hallbert; Brian F. Gore

    2006-05-01

    This paper summarizes an emerging collaboration between Idaho National Laboratory and NASA Ames Research Center regarding the utilization of high-fidelity MIDAS simulations for modeling control room crew performance at nuclear power plants. The key envisioned uses for MIDAS-based control room simulations are: (i) the estimation of human error with novel control room equipment and configurations, (ii) the investigative determination of risk significance in recreating past event scenarios involving control room operating crews, and (iii) the certification of novel staffing levels in control rooms. It is proposed that MIDAS serves as a key component for the effective modeling of risk in next generation control rooms.

  9. Behavior genetic modeling of human fertility

    DEFF Research Database (Denmark)

    Rodgers, J L; Kohler, H P; Kyvik, K O

    2001-01-01

    Try) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males......Behavior genetic designs and analysis can be used to address issues of central importance to demography. We use this methodology to document genetic influence on human fertility. Our data come from Danish twin pairs born from 1953 to 1959, measured on age at first attempt to get pregnant (First...

  10. Genetically engineered mouse models and human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ng Alvin JM

    2012-10-01

    Full Text Available Abstract Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics.

  11. Modeling Oxygen Transport in the Human Placenta

    Science.gov (United States)

    Serov, Alexander; Filoche, Marcel; Salafia, Carolyn; Grebenkov, Denis

    Efficient functioning of the human placenta is crucial for the favorable pregnancy outcome. We construct a 3D model of oxygen transport in the placenta based on its histological cross-sections. The model accounts for both diffusion and convention of oxygen in the intervillous space and allows one to estimate oxygen uptake of a placentone. We demonstrate the existence of an optimal villi density maximizing the uptake and explain it as a trade-off between the incoming oxygen flow and the absorbing villous surface. Calculations performed for arbitrary shapes of fetal villi show that only two geometrical characteristics - villi density and the effective villi radius - are required to predict fetal oxygen uptake. Two combinations of physiological parameters that determine oxygen uptake are also identified: maximal oxygen inflow of a placentone and the Damköhler number. An automatic image analysis method is developed and applied to 22 healthy placental cross-sections demonstrating that villi density of a healthy human placenta lies within 10% of the optimal value, while overall geometry efficiency is rather low (around 30-40%). In a perspective, the model can constitute the base of a reliable tool of post partum oxygen exchange efficiency assessment in the human placenta. Also affiliated with Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA.

  12. Biomedical Simulation Models of Human Auditory Processes

    Science.gov (United States)

    Bicak, Mehmet M. A.

    2012-01-01

    Detailed acoustic engineering models that explore noise propagation mechanisms associated with noise attenuation and transmission paths created when using hearing protectors such as earplugs and headsets in high noise environments. Biomedical finite element (FE) models are developed based on volume Computed Tomography scan data which provides explicit external ear, ear canal, middle ear ossicular bones and cochlea geometry. Results from these studies have enabled a greater understanding of hearing protector to flesh dynamics as well as prioritizing noise propagation mechanisms. Prioritization of noise mechanisms can form an essential framework for exploration of new design principles and methods in both earplug and earcup applications. These models are currently being used in development of a novel hearing protection evaluation system that can provide experimentally correlated psychoacoustic noise attenuation. Moreover, these FE models can be used to simulate the effects of blast related impulse noise on human auditory mechanisms and brain tissue.

  13. Modelling the evolution of human trail systems

    Science.gov (United States)

    Helbing, Dirk; Keltsch, Joachim; Molnár, Péter

    1997-07-01

    Many human social phenomena, such as cooperation, the growth of settlements, traffic dynamics and pedestrian movement, appear to be accessible to mathematical descriptions that invoke self-organization. Here we develop a model of pedestrian motion to explore the evolution of trails in urban green spaces such as parks. Our aim is to address such questions as what the topological structures of these trail systems are, and whether optimal path systems can be predicted for urban planning. We use an `active walker' model that takes into account pedestrian motion and orientation and the concomitant feedbacks with the surrounding environment. Such models have previously been applied to the study of complex structure formation in physical, chemical and biological systems. We find that our model is able to reproduce many of the observed large-scale spatial features of trail systems.

  14. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  15. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2014-07-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  16. Modeling human influenza infection in the laboratory

    Directory of Open Access Journals (Sweden)

    Radigan KA

    2015-08-01

    Full Text Available Kathryn A Radigan,1 Alexander V Misharin,2 Monica Chi,1 GR Scott Budinger11Division of Pulmonary and Critical Care Medicine, 2Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection.Keywords: mice, ferret, influenza, animal model, biosafety

  17. Modeling learned categorical perception in human vision.

    Science.gov (United States)

    Casey, Matthew C; Sowden, Paul T

    2012-09-01

    A long standing debate in cognitive neuroscience has been the extent to which perceptual processing is influenced by prior knowledge and experience with a task. A converging body of evidence now supports the view that a task does influence perceptual processing, leaving us with the challenge of understanding the locus of, and mechanisms underpinning, these influences. An exemplar of this influence is learned categorical perception (CP), in which there is superior perceptual discrimination of stimuli that are placed in different categories. Psychophysical experiments on humans have attempted to determine whether early cortical stages of visual analysis change as a result of learning a categorization task. However, while some results indicate that changes in visual analysis occur, the extent to which earlier stages of processing are changed is still unclear. To explore this issue, we develop a biologically motivated neural model of hierarchical vision processes consisting of a number of interconnected modules representing key stages of visual analysis, with each module learning to exhibit desired local properties through competition. With this system level model, we evaluate whether a CP effect can be generated with task influence to only the later stages of visual analysis. Our model demonstrates that task learning in just the later stages is sufficient for the model to exhibit the CP effect, demonstrating the existence of a mechanism that requires only a high-level of task influence. However, the effect generalizes more widely than is found with human participants, suggesting that changes to earlier stages of analysis may also be involved in the human CP effect, even if these are not fundamental to the development of CP. The model prompts a hybrid account of task-based influences on perception that involves both modifications to the use of the outputs from early perceptual analysis along with the possibility of changes to the nature of that early analysis itself

  18. [Emerging deep-seated fungal infection, trichosporonosis].

    Science.gov (United States)

    Tokimatsu, Issei; Kadota, Jun-ichi

    2006-05-01

    Deep-seated trichosporonosis is a lethal opportunistic infection occasionally found in immunocompromised patients, particularly those who are neutropenic due to cytotoxic therapy for hematological malignancies. Trichosporon asahii is considered the principal etiologic agent of non-Candida fungemia and disseminated trichosporonosis in Japan. This infection may disseminate to multiple organs and difficult to diagnosis and treat. Because clinical findings and courses of trichosporonosis are similar to disseminated candidasis, it is impossible to distinguish these infections without fungal isolation. Monotherapy of amphotericin B is thought to be unsuccessful for this infection, and new antifungal agents echinocandins are also not active against Trichosporon species. Some clinical reports and animal models suggest that triazoles and combination therapies are most effective drugs against trichosporonosis. Recently, T. asahii isolates with reduced susceptibility in vitro to multi-antifungal agents are reported. T. asahii is the allergen of summer-type hypersensitivity pneumonitis and sometimes isolated from the houses environments, but it is not clear that the environmental strains directly infect to human. There is no clinical evidence that Trichosporon is the common outbreak pathogen in the hospital. However, it is necessary for a clinician to pay enough care as the lethal infections in immunocompromised patients.

  19. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  20. Modulation of host-cell MAPkinase signaling during fungal infection

    Directory of Open Access Journals (Sweden)

    Nir Osherov

    2015-10-01

    Full Text Available Fungal infections contribute substantially to human suffering and mortality. The interaction between fungal pathogens and their host involves the invasion and penetration of the surface epithelium, activation of cells of the innate immune system and the generation of an effective response to block infection. Numerous host-cell signaling pathways are activated during fungal infection. This review will focus on the main fungal pathogens Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans and their ability to activate the host MAP-kinase signaling pathways leading to cytokine secretion, increased cell motility and killing of the pathogen. Both epithelial and innate immune cells specifically recognize fungal antigens and in particular cell surface polysaccharides such as β-glucans and react to them by activating multiple signaling pathways, including those containing MAP-kinase modules. Recent findings suggest that the host response to fungal infection utilizes the MAP-kinase pathway to differentiate between commensal and pathogenic fungi to selectively react only to the pathogenic forms. However, the paucity of relevant publications strongly emphasize that our understanding of host MAP-kinase signaling in response to fungal infection is still at a very early stage. It is clear, based on studies of host MAP-kinase signaling during viral and bacterial infections, that in fungi as well, a wealth of exciting findings await us.

  1. Assessment of relevant fungal species in clinical solid wastes.

    Science.gov (United States)

    Noman, Efaq Ali; Al-Gheethi, A A; Rahman, Nik Norulaini Nik Ab; Nagao, H; Ab Kadir, M O

    2016-10-01

    The study aimed to determine the fungal diversity in clinical waste samples from a healthcare facility in Penang Malaysia. Different fungi species were detected in 83.75 % of the 92 clinical waste samples that were screened from different sections of the healthcare facility. One hundred fifty fungal isolates comprising of 8 genera and 36 species were obtained. They were purified by using single spore isolation technique. Subsequently, the isolates were identified by phenotypic method based on morphological and culture characteristics on different culture media. Among all fungal isolates, Aspergillus spp. in section Nigri 10.2 %, Aspergillus niger 9.5 %, Aspergillus fumigatus 8.8 %, Penicillium. simplicissium 8 %, Aspergillus tubingensis 7.3 %, Aspergillus terreus var. terreus 6.6 %, Penicillium waksmanii 5.9 % and Curvularia lunata 6.5 % were the most frequent. Among five sections of the Wellness Centre, the clinical wastes collected from the diagnostic labs of haematology section had the highest numbers of fungal species (29 species). Glove wastes had the highest numbers of fungal species (19 species) among 17 types of clinical wastes screened. Among all fungal species, Aspergillus spp. exhibited higher growth at 37 °C than at 28 °C, indicating the potential of these opportunistic fungi to cause diseases in human. These results indicated the potential of hospital wastes as reservoirs for fungal species.

  2. Computational Models to Synthesize Human Walking

    Institute of Scientific and Technical Information of China (English)

    Lei Ren; David Howard; Laurence Kenney

    2006-01-01

    The synthesis of human walking is of great interest in biomechanics and biomimetic engineering due to its predictive capabilities and potential applications in clinical biomechanics, rehabilitation engineering and biomimetic robotics. In this paper,the various methods that have been used to synthesize humanwalking are reviewed from an engineering viewpoint. This involves a wide spectrum of approaches, from simple passive walking theories to large-scale computational models integrating the nervous, muscular and skeletal systems. These methods are roughly categorized under four headings: models inspired by the concept of a CPG (Central Pattern Generator), methods based on the principles of control engineering, predictive gait simulation using optimisation, and models inspired by passive walking theory. The shortcomings and advantages of these methods are examined, and future directions are discussed in the context of providing insights into the neural control objectives driving gait and improving the stability of the predicted gaits. Future advancements are likely to be motivated by improved understanding of neural control strategies and the subtle complexities of the musculoskeletal system during human locomotion. It is only a matter of time before predictive gait models become a practical and valuable tool in clinical diagnosis, rehabilitation engineering and robotics.

  3. A dynamic model of human physiology

    Science.gov (United States)

    Green, Melissa; Kaplan, Carolyn; Oran, Elaine; Boris, Jay

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  4. Modeling and simulation of the human eye

    Science.gov (United States)

    Duran, R.; Ventura, L.; Nonato, L.; Bruno, O.

    2007-02-01

    The computational modeling of the human eye has been wide studied for different sectors of the scientific and technological community. One of the main reasons for this increasing interest is the possibility to reproduce eye optic properties by means of computational simulations, becoming possible the development of efficient devices to treat and to correct the problems of the vision. This work explores this aspect still little investigated of the modeling of the visual system, considering a computational sketch that make possible the use of real data in the modeling and simulation of the human visual system. This new approach makes possible the individual inquiry of the optic system, assisting in the construction of new techniques used to infer vital data in medical investigations. Using corneal topography to collect real data from patients, a computational model of cornea is constructed and a set of simulations were build to ensure the correctness of the system and to investigate the effect of corneal abnormalities in retinal image formation, such as Plcido Discs, Point Spread Function, Wave front and the projection of a real image and it's visualization on retina.

  5. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    Science.gov (United States)

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-10-22

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.

  6. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens

    Directory of Open Access Journals (Sweden)

    Shinji Amari

    2013-01-01

    Full Text Available The three-dimensional (3D structures of human leukocyte antigen (HLA molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  7. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens.

    Science.gov (United States)

    Amari, Shinji; Kataoka, Ryoichi; Ikegami, Takashi; Hirayama, Noriaki

    2013-01-01

    The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  8. Model human heart or brain signals

    CERN Document Server

    Tuncay, Caglar

    2008-01-01

    A new model is suggested and used to mimic various spatial or temporal designs in biological or non biological formations where the focus is on the normal or irregular electrical signals coming from human heart (ECG) or brain (EEG). The electrical activities in several muscles (EMG) or neurons or other organs of human or various animals, such as lobster pyloric neuron, guinea pig inferior olivary neuron, sepia giant axon and mouse neocortical pyramidal neuron and some spatial formations are also considered (in Appendix). In the biological applications, several elements (cells or tissues) in an organ are taken as various entries in a representative lattice (mesh) where the entries are connected to each other in terms of some molecular diffusions or electrical potential differences. The biological elements evolve in time (with the given tissue or organ) in terms of the mentioned connections (interactions) besides some individual feedings. The anatomical diversity of the species (or organs) is handled in terms o...

  9. The quantitative modelling of human spatial habitability

    Science.gov (United States)

    Wise, J. A.

    1985-01-01

    A model for the quantitative assessment of human spatial habitability is presented in the space station context. The visual aspect assesses how interior spaces appear to the inhabitants. This aspect concerns criteria such as sensed spaciousness and the affective (emotional) connotations of settings' appearances. The kinesthetic aspect evaluates the available space in terms of its suitability to accommodate human movement patterns, as well as the postural and anthrometric changes due to microgravity. Finally, social logic concerns how the volume and geometry of available space either affirms or contravenes established social and organizational expectations for spatial arrangements. Here, the criteria include privacy, status, social power, and proxemics (the uses of space as a medium of social communication).

  10. Fungal biodiversity to biotechnology.

    Science.gov (United States)

    Chambergo, Felipe S; Valencia, Estela Y

    2016-03-01

    Fungal habitats include soil, water, and extreme environments. With around 100,000 fungus species already described, it is estimated that 5.1 million fungus species exist on our planet, making fungi one of the largest and most diverse kingdoms of eukaryotes. Fungi show remarkable metabolic features due to a sophisticated genomic network and are important for the production of biotechnological compounds that greatly impact our society in many ways. In this review, we present the current state of knowledge on fungal biodiversity, with special emphasis on filamentous fungi and the most recent discoveries in the field of identification and production of biotechnological compounds. More than 250 fungus species have been studied to produce these biotechnological compounds. This review focuses on three of the branches generally accepted in biotechnological applications, which have been identified by a color code: red, green, and white for pharmaceutical, agricultural, and industrial biotechnology, respectively. We also discuss future prospects for the use of filamentous fungi in biotechnology application.

  11. The quantitative modelling of human spatial habitability

    Science.gov (United States)

    Wise, James A.

    1988-01-01

    A theoretical model for evaluating human spatial habitability (HuSH) in the proposed U.S. Space Station is developed. Optimizing the fitness of the space station environment for human occupancy will help reduce environmental stress due to long-term isolation and confinement in its small habitable volume. The development of tools that operationalize the behavioral bases of spatial volume for visual kinesthetic, and social logic considerations is suggested. This report further calls for systematic scientific investigations of how much real and how much perceived volume people need in order to function normally and with minimal stress in space-based settings. The theoretical model presented in this report can be applied to any size or shape interior, at any scale of consideration, for the Space Station as a whole to an individual enclosure or work station. Using as a point of departure the Isovist model developed by Dr. Michael Benedikt of the U. of Texas, the report suggests that spatial habitability can become as amenable to careful assessment as engineering and life support concerns.

  12. MODELING HUMAN COMPREHENSION OF DATA VISUALIZATIONS.

    Energy Technology Data Exchange (ETDEWEB)

    Matzen, Laura E.; Haass, Michael Joseph; Divis, Kristin Marie; Wilson, Andrew T.

    2017-09-01

    This project was inspired by two needs. The first is a need for tools to help scientists and engineers to design effective data visualizations for communicating information, whether to the user of a system, an analyst who must make decisions based on complex data, or in the context of a technical report or publication. Most scientists and engineers are not trained in visualization design, and they could benefit from simple metrics to assess how well their visualization's design conveys the intended message. In other words, will the most important information draw the viewer's attention? The second is the need for cognition-based metrics for evaluating new types of visualizations created by researchers in the information visualization and visual analytics communities. Evaluating visualizations is difficult even for experts. However, all visualization methods and techniques are intended to exploit the properties of the human visual system to convey information efficiently to a viewer. Thus, developing evaluation methods that are rooted in the scientific knowledge of the human visual system could be a useful approach. In this project, we conducted fundamental research on how humans make sense of abstract data visualizations, and how this process is influenced by their goals and prior experience. We then used that research to develop a new model, the Data Visualization Saliency Model, that can make accurate predictions about which features in an abstract visualization will draw a viewer's attention. The model is an evaluation tool that can address both of the needs described above, supporting both visualization research and Sandia mission needs.

  13. Managing acute invasive fungal sinusitis.

    Science.gov (United States)

    Dwyhalo, Kristina M; Donald, Carrlene; Mendez, Anthony; Hoxworth, Joseph

    2016-01-01

    Acute invasive fungal sinusitis is the most aggressive form of fungal sinusitis and can be fatal, especially in patients who are immunosuppressed. Early diagnosis and intervention are crucial and potentially lifesaving, so primary care providers must maintain a high index of suspicion for this disease. Patients may need to be admitted to the hospital for IV antifungal therapy and surgical debridement.

  14. Current management of fungal infections.

    NARCIS (Netherlands)

    Meis, J.F.G.M.; Verweij, P.E.

    2001-01-01

    The management of superficial fungal infections differs significantly from the management of systemic fungal infections. Most superficial infections are treated with topical antifungal agents, the choice of agent being determined by the site and extent of the infection and by the causative organism,

  15. The evolution of fungal epiphytes

    NARCIS (Netherlands)

    Hongsanan, S.; Sánchez-Ramírez, S.; Crous, P.W.; Ariyawansa, H.A.; Zhao, R.L.; Hyde, K.D.

    2016-01-01

    Fungal epiphytes are a polyphyletic group found on the surface of plants, particularly on leaves, with a worldwide distribution. They belong in the phylum Ascomycota, which contains the largest known number of fungal genera. There has been little research dating the origins of the common ancestors o

  16. Mouse Model of Human Hereditary Pancreatitis

    Science.gov (United States)

    2016-09-01

    models that recapitulate the human disease . Therefore, we introduced mutations in the endogenous mouse T7 cationic trypsinogen gene and obtained several...ACCOMPLISHMENTS: What were the major goals of the project? Our original proposal had three specific aims. Aim 1. Identify and biochemically characterize...pancreatitis in mutant mice which do not develop spontaneous disease (strains T7-D23del-Cre, T7-D23del-Neo, T7-K24R-Cre and T7- K24R-Neo), will be

  17. Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models

    OpenAIRE

    Bility, Moses T.; Li, Feng; Cheng, Liang; Su, Lishan

    2013-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system’s contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mous...

  18. Standard methods for fungal brood disease research

    DEFF Research Database (Denmark)

    Jensen, Annette Bruun; Aronstein, Kathrine; Manuel Flores, Jose

    2013-01-01

    Chalkbrood and stonebrood are two fungal diseases associated with honey bee brood. Chalkbrood, caused by Ascosphaera apis, is a common and widespread disease that can result in severe reduction of emerging worker bees and thus overall colony productivity. Stonebrood is caused by Aspergillus spp. ...... interactions. We give guidelines on the preferred methods used in current research and the application of molecular techniques. We have added photographs, drawings and illustrations to assist bee-extension personnel and bee scientists in the control of these two diseases....... tissues upon inhalation by humans. In the current chapter we describe the honey bee disease symptoms of these fungal pathogens. In addition, we provide research methodologies and protocols for isolating and culturing, in vivo and in vitro assays that are commonly used to study these host pathogen...

  19. A modular approach to numerical human body modeling

    NARCIS (Netherlands)

    Forbes, P.A.; Griotto, G.; Rooij, L. van

    2007-01-01

    The choice of a human body model for a simulated automotive impact scenario must take into account both accurate model response and computational efficiency as key factors. This study presents a "modular numerical human body modeling" approach which allows the creation of a customized human body mod

  20. A modular approach to numerical human body modeling

    NARCIS (Netherlands)

    Forbes, P.A.; Griotto, G.; Rooij, L. van

    2007-01-01

    The choice of a human body model for a simulated automotive impact scenario must take into account both accurate model response and computational efficiency as key factors. This study presents a "modular numerical human body modeling" approach which allows the creation of a customized human body

  1. Generative models: Human embryonic stem cells and multiple modeling relations.

    Science.gov (United States)

    Fagan, Melinda Bonnie

    2016-04-01

    Model organisms are at once scientific models and concrete living things. It is widely assumed by philosophers of science that (1) model organisms function much like other kinds of models, and (2) that insofar as their scientific role is distinctive, it is in virtue of representing a wide range of biological species and providing a basis for generalizations about those targets. This paper uses the case of human embryonic stem cells (hESC) to challenge both assumptions. I first argue that hESC can be considered model organisms, analogous to classic examples such as Escherichia coli and Drosophila melanogaster. I then discuss four contrasts between the epistemic role of hESC in practice, and the assumptions about model organisms noted above. These contrasts motivate an alternative view of model organisms as a network of systems related constructively and developmentally to one another. I conclude by relating this result to other accounts of model organisms in recent philosophy of science. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Human factors engineering program review model

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element.

  3. Conditional Lineage Ablation to Model Human Diseases

    Science.gov (United States)

    Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

    1998-09-01

    Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

  4. A human neurodevelopmental model for Williams syndrome.

    Science.gov (United States)

    Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

    2016-08-18

    Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

  5. Integrated Human Futures Modeling in Egypt

    Energy Technology Data Exchange (ETDEWEB)

    Passell, Howard D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Aamir, Munaf Syed [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bernard, Michael Lewis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Beyeler, Walter E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Fellner, Karen Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hayden, Nancy Kay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jeffers, Robert Fredric [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Keller, Elizabeth James Kistin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Malczynski, Leonard A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mitchell, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Silver, Emily [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tidwell, Vincent C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Villa, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vugrin, Eric D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Engelke, Peter [Atlantic Council, Washington, D.C. (United States); Burrow, Mat [Atlantic Council, Washington, D.C. (United States); Keith, Bruce [United States Military Academy, West Point, NY (United States)

    2016-01-01

    The Integrated Human Futures Project provides a set of analytical and quantitative modeling and simulation tools that help explore the links among human social, economic, and ecological conditions, human resilience, conflict, and peace, and allows users to simulate tradeoffs and consequences associated with different future development and mitigation scenarios. In the current study, we integrate five distinct modeling platforms to simulate the potential risk of social unrest in Egypt resulting from the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile in Ethiopia. The five platforms simulate hydrology, agriculture, economy, human ecology, and human psychology/behavior, and show how impacts derived from development initiatives in one sector (e.g., hydrology) might ripple through to affect other sectors and how development and security concerns may be triggered across the region. This approach evaluates potential consequences, intended and unintended, associated with strategic policy actions that span the development-security nexus at the national, regional, and international levels. Model results are not intended to provide explicit predictions, but rather to provide system-level insight for policy makers into the dynamics among these interacting sectors, and to demonstrate an approach to evaluating short- and long-term policy trade-offs across different policy domains and stakeholders. The GERD project is critical to government-planned development efforts in Ethiopia but is expected to reduce downstream freshwater availability in the Nile Basin, fueling fears of negative social and economic impacts that could threaten stability and security in Egypt. We tested these hypotheses and came to the following preliminary conclusions. First, the GERD will have an important short-term impact on water availability, food production, and hydropower production in Egypt, depending on the short- term reservoir fill rate. Second, the GERD will have a very small impact on

  6. Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities.

    Science.gov (United States)

    Traven, Ana; Jänicke, Amrei; Harrison, Paul; Swaminathan, Angavai; Seemann, Torsten; Beilharz, Traude H

    2012-01-01

    Understanding multicellular fungal structures is important for designing better strategies against human fungal pathogens. For example, the ability to form multicellular biofilms is a key virulence property of the yeast Candida albicans. C. albicans biofilms form on indwelling medical devices and are drug resistant, causing serious infections in hospital settings. Multicellular fungal communities are heterogeneous, consisting of cells experiencing different environments. Heterogeneity is likely important for the phenotypic characteristics of communities, yet it is poorly understood. Here we used colonies of the yeast Saccharomyces cerevisiae as a model fungal multicellular structure. We fractionated the outside colony layers from the cells in the center by FACS, using a Cit1-GFP marker expressed exclusively on the outside. Transcriptomics analysis of the two subpopulations revealed that the outside colony layers are actively growing by fermentative metabolism, while the cells residing on the inside are in a resting state and experience changes to mitochondrial activity. Our data shows several parallels with C. albicans biofilms providing insight into the contributions of heterogeneity to biofilm phenotypes. Hallmarks of C. albicans biofilms - the expression of ribosome and translation functions and activation of glycolysis and ergosterol biosynthesis occur on the outside of colonies, while expression of genes associates with sulfur assimilation is observed in the colony center. Cell wall restructuring occurs in biofilms, and cell wall functions are enriched in both fractions: the outside cells display enrichment of cell wall biosynthesis enzymes and cell wall proteins, while the inside cells express cell wall degrading enzymes. Our study also suggests that noncoding transcription and posttranscriptional mRNA regulation play important roles during growth of yeast in colonies, setting the scene for investigating these pathways in the development of multicellular

  7. Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities.

    Directory of Open Access Journals (Sweden)

    Ana Traven

    Full Text Available Understanding multicellular fungal structures is important for designing better strategies against human fungal pathogens. For example, the ability to form multicellular biofilms is a key virulence property of the yeast Candida albicans. C. albicans biofilms form on indwelling medical devices and are drug resistant, causing serious infections in hospital settings. Multicellular fungal communities are heterogeneous, consisting of cells experiencing different environments. Heterogeneity is likely important for the phenotypic characteristics of communities, yet it is poorly understood. Here we used colonies of the yeast Saccharomyces cerevisiae as a model fungal multicellular structure. We fractionated the outside colony layers from the cells in the center by FACS, using a Cit1-GFP marker expressed exclusively on the outside. Transcriptomics analysis of the two subpopulations revealed that the outside colony layers are actively growing by fermentative metabolism, while the cells residing on the inside are in a resting state and experience changes to mitochondrial activity. Our data shows several parallels with C. albicans biofilms providing insight into the contributions of heterogeneity to biofilm phenotypes. Hallmarks of C. albicans biofilms - the expression of ribosome and translation functions and activation of glycolysis and ergosterol biosynthesis occur on the outside of colonies, while expression of genes associates with sulfur assimilation is observed in the colony center. Cell wall restructuring occurs in biofilms, and cell wall functions are enriched in both fractions: the outside cells display enrichment of cell wall biosynthesis enzymes and cell wall proteins, while the inside cells express cell wall degrading enzymes. Our study also suggests that noncoding transcription and posttranscriptional mRNA regulation play important roles during growth of yeast in colonies, setting the scene for investigating these pathways in the development

  8. SVM Model for Identification of human GPCRs

    CERN Document Server

    Shrivastava, Sonal; Malik, M M

    2010-01-01

    G-protein coupled receptors (GPCRs) constitute a broad class of cell-surface receptors in eukaryotes and they possess seven transmembrane a-helical domains. GPCRs are usually classified into several functionally distinct families that play a key role in cellular signalling and regulation of basic physiological processes. We can develop statistical models based on these common features that can be used to classify proteins, to predict new members, and to study the sequence-function relationship of this protein function group. In this study, SVM based classification model has been developed for the identification of human gpcr sequences. Sequences of Level 1 subfamilies of Class A rhodopsin is considered as case study. In the present study, an attempt has been made to classify GPCRs on the basis of species. The present study classifies human gpcr sequences with rest of the species available in GPCRDB. Classification is based on specific information derived from the n-terminal and extracellular loops of the sequ...

  9. Simple models of human brain functional networks.

    Science.gov (United States)

    Vértes, Petra E; Alexander-Bloch, Aaron F; Gogtay, Nitin; Giedd, Jay N; Rapoport, Judith L; Bullmore, Edward T

    2012-04-10

    Human brain functional networks are embedded in anatomical space and have topological properties--small-worldness, modularity, fat-tailed degree distributions--that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas.

  10. Delayed Random Walks: Modeling Human Posture Control

    Science.gov (United States)

    Ohira, Toru

    1998-03-01

    We consider a phenomenological description of a noisy trajectory which appears on a stabiliogram platform during human postural sway. We hypothesize that this trajectory arises due to a mixture of uncontrollable noise and a corrective delayed feedback to an upright position. Based on this hypothesis, we model the process with a biased random walk whose transition probability depends on its position at a fixed time delay in the past, which we call a delayed random walk. We first introduce a very simple model (T. Ohira and J. G. Milton, Phys.Rev.E. 52), 3277, (1995), which can nevertheless capture the rough qualitative features of the two--point mean square displacement of experimental data with reasonable estimation of delay time. Then, we discuss two approaches toward better capturing and understanding of the experimental data. The first approach is an extension of the model to include a spatial displacement threshold from the upright position below which no or only weak corrective feedback motion takes place. This can be incorporated into an extended delayed random walk model. Numerical simulations show that this extended model can better capture the three scaling region which appears in the two--point mean square displacement. The other approach studied the autocorrelation function of the experimental data, which shows oscillatory behavior. We recently investigated a delayed random walk model whose autocorrelation function has analytically tractable oscillatory behavior (T. Ohira, Phys.Rev.E. 55), R1255, (1997). We discuss how this analytical understanding and its application to delay estimation (T. Ohira and R. Sawatari, Phys.Rev.E. 55), R2077, (1997) could possibly be used to further understand the postural sway data.

  11. Automatic Modeling of Virtual Humans and Body Clothing

    Institute of Scientific and Technical Information of China (English)

    Nadia Magnenat-Thalmann; Hyewon Seo; Frederic Cordier

    2004-01-01

    Highly realistic virtual human models are rapidly becoming commonplace in computer graphics.These models, often represented by complex shape and requiring labor-intensive process, challenge the problem of automatic modeling. The problem and solutions to automatic modeling of animatable virtual humans are studied. Methods for capturing the shape of real people, parameterization techniques for modeling static shape (the variety of human body shapes) and dynamic shape (how the body shape changes as it moves) of virtual humans are classified, summarized and compared. Finally, methods for clothed virtual humans are reviewed.

  12. Foliar and fungal 15N:14N ratios reflect development of mycorrhizae and nitrogen supply during primary succession: testing analytical models.

    Science.gov (United States)

    Hobbie, Erik A; Jumpponen, Ari; Trappe, Jim

    2005-12-01

    per thousand. Plants, fungi and soil were at least 4 per thousand higher in delta15N from the mature site than in recently exposed sites. On both the forefront and the mature site, host-specific ectomycorrhizal fungi had higher delta15N values than ectomycorrhizal fungi with a broad host range. From these isotopic patterns, we conclude: (1) large enrichments in 15N of many ectomycorrhizal fungi relative to co-occurring ectomycorrhizal plants are best explained by treating the plant-fungal-soil system as a closed system with a discrimination against 15N of 8-10 per thousand during transfer from fungi to plants, (2) based on models of 15N mass balance, ericoid and ectomycorrhizal fungi retain up to two-thirds of the N in the plant-mycorrhizal system under the N-limited conditions at forefront sites, (3) sporocarps are probably enriched in 15N by an additional 3 per thousand relative to available nitrogen, and (4) host-specific ectomycorrhizal fungi may transfer more N to plant hosts than non-host-specific ectomycorrhizal fungi. Our study confirms that nitrogen isotopes are a powerful tool for probing nitrogen dynamics between mycorrhizal fungi and associated plants.

  13. The Application of Humanized Mouse Models for the Study of Human Exclusive Viruses.

    Science.gov (United States)

    Vahedi, Fatemeh; Giles, Elizabeth C; Ashkar, Ali A

    2017-01-01

    The symbiosis between humans and viruses has allowed human tropic pathogens to evolve intricate means of modulating the human immune response to ensure its survival among the human population. In doing so, these viruses have developed profound mechanisms that mesh closely with our human biology. The establishment of this intimate relationship has created a species-specific barrier to infection, restricting the virus-associated pathologies to humans. This specificity diminishes the utility of traditional animal models. Humanized mice offer a model unique to all other means of study, providing an in vivo platform for the careful examination of human tropic viruses and their interaction with human cells and tissues. These types of animal models have provided a reliable medium for the study of human-virus interactions, a relationship that could otherwise not be investigated without questionable relevance to humans.

  14. Modeling the human prothrombinase complex components

    Science.gov (United States)

    Orban, Tivadar

    Thrombin generation is the culminating stage of the blood coagulation process. Thrombin is obtained from prothrombin (the substrate) in a reaction catalyzed by the prothrombinase complex (the enzyme). The prothrombinase complex is composed of factor Xa (the enzyme), factor Va (the cofactor) associated in the presence of calcium ions on a negatively charged cell membrane. Factor Xa, alone, can activate prothrombin to thrombin; however, the rate of conversion is not physiologically relevant for survival. Incorporation of factor Va into prothrombinase accelerates the rate of prothrombinase activity by 300,000-fold, and provides the physiological pathway of thrombin generation. The long-term goal of the current proposal is to provide the necessary support for the advancing of studies to design potential drug candidates that may be used to avoid development of deep venous thrombosis in high-risk patients. The short-term goals of the present proposal are to (1) to propose a model of a mixed asymmetric phospholipid bilayer, (2) expand the incomplete model of human coagulation factor Va and study its interaction with the phospholipid bilayer, (3) to create a homology model of prothrombin (4) to study the dynamics of interaction between prothrombin and the phospholipid bilayer.

  15. Animal models for human craniofacial malformations.

    Science.gov (United States)

    Johnston, M C; Bronsky, P T

    1991-01-01

    Holoprosencephaly malformations, of which the fetal alcohol syndrome appears to be a mild form, can result from medial anterior neural plate deficiencies as demonstrated in an ethanol treated animal model. These malformations are associated with more medial positioning of the nasal placodes and resulting underdevelopment or absence of the medial nasal prominences (MNPs) and their derivatives. Malformations seen in the human retinoic acid syndrome (RAS) can be produced by administration of the drug 13-cis-retinoic acid in animals. Primary effects on neural crest cells account for most of these RAS malformations. Many of the malformations seen in the RAS are similar to those of hemifacial microsomia, suggesting similar neural crest involvement. Excessive cell death, apparently limited to trigeminal ganglion neuroblasts of placodal origin, follows 13-cis retinoic acid administration at the time of ganglion formation and leads to malformations virtually identical to those of the Treacher Collins syndrome (TCS). Secondary effects on neural crest cells in the area of the ganglion appear to be responsible for the TCS malformations. Malformations of the DiGeorge Syndrome are similar to those of the RAS and can be produced in mice by ethanol administration or by "knocking out" a homeobox gene (box 1.5). Human and animal studies indicate that cleft lips of multifactorial etiology may be generically susceptible because of small MNP)s or other MNP developmental alterations, such as those found in A/J mice, that make prominence contact more difficult. Experimental maternal hypoxia in mice indicates that cigarette smoking may increase the incidence of cleft lip by interfering with morphogenetic movements. Other human cleft lips may result from the action of a single major gene coding for TGF-alpha variants. A study with mouse palatal shelves in culture and other information suggest that a fusion problem may be involved.

  16. Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models.

    Science.gov (United States)

    Bility, Moses T; Li, Feng; Cheng, Liang; Su, Lishan

    2013-08-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system's contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mouse model engrafted with both human immune and human liver cells is needed to study infection and immunopathogenesis of HBV/HCV infection in vivo. We have recently developed the humanized mouse model with both human immune and human liver cells (AFC8-hu HSC/Hep) to study immunopathogenesis and therapy of HCV infection in vivo. In this review, we summarize the current models of HBV/HCV infection and their limitations in immunopathogenesis. We will then present our recent findings of HCV infection and immunopathogenesis in the AFC8-hu HSC/Hep mouse, which supports HCV infection, human T-cell response and associated liver pathogenesis. Inoculation of humanized mice with primary HCV isolates resulted in long-term HCV infection. HCV infection induced elevated infiltration of human immune cells in the livers of HCV-infected humanized mice. HCV infection also induced HCV-specific T-cell immune response in lymphoid tissues of humanized mice. Additionally, HCV infection induced liver fibrosis in humanized mice. Anti-human alpha smooth muscle actin (αSMA) staining showed elevated human hepatic stellate cell activation in HCV-infected humanized mice. We discuss the limitation and future improvements of the AFC8-hu HSC/Hep mouse model and its application in evaluating novel therapeutics, as well as studying both HCV and HBV infection, human immune responses, and associated human liver fibrosis and cancer.

  17. Modeling and remodeling of human extraction sockets.

    Science.gov (United States)

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Bozzi, Leopoldo; Liljenberg, Birgitta; Lindhe, Jan

    2008-07-01

    The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

  18. In Vitro Model of Human Choroidal Neovascular

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Choroidal capillary endothelia cell (CEC) plays a critical role in the development of choroidal neovascularization which is one of the major causes of blindness. An effective method for CEC cultivation was proposed.The isolation of human choroidal CECs using micro dissection followed by the use of superparamagnetic beads (Dynabeads) coated with the CD 31, which selectively binds to the endothelial cell surface. Cells bound to beads were isolated using a magnetic particle concentrator. The CECs were planted into type Ⅳ collagen coated 24 well plates. The results show that the primary cultured CEC is induced to tube formation in collagen Ⅳ coated environment, which can be presented as an in vitro model of choroidal neovascularization.

  19. Molecular Modeling of Prion Transmission to Humans

    Directory of Open Access Journals (Sweden)

    Etienne Levavasseur

    2014-10-01

    Full Text Available Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.

  20. Design of a Human Reliability Assessment model for structural engineering

    NARCIS (Netherlands)

    De Haan, J.; Terwel, K.C.; Al-Jibouri, S.H.S.

    2013-01-01

    It is generally accepted that humans are the “weakest link” in structural design and construction processes. Despite this, few models are available to quantify human error within engineering processes. This paper demonstrates the use of a quantitative Human Reliability Assessment model within struct

  1. Analysis of rear end impact using mathematical human modelling

    NARCIS (Netherlands)

    Happee, R.; Meijer, R.; Horst, M.J. van der; Ono, K.; Yamazaki, K.

    2000-01-01

    At TNO an omni-directional mathematical human body model has been developed. Until now this human model has been validated for frontal and lateral loading using response data of volunteer and post mortem human subject (PMHS) sled tests. For rearward loading it has been validated for high speed impac

  2. Modified atmospheric conditions controlling fungal growth on cheese

    DEFF Research Database (Denmark)

    Nielsen, Per Væggemose

    1997-01-01

    2 level, relative humidity and temperature) and the composition of the cheese. All fungal species commonly found on cheese, starter cultures as well as contaminants, were examined.The most important factors influencing fungal growth are temperature, water activity of the medium and the carbon......Effective control of fungal growth on cheese under storage conditions is of great concern for the dairy industry. Therefore we designed a research project together with the Danish dairy industry on modelling fungal growth on cheese as affected by the combined effect of storage conditions (O2 and CO...... a competitive advantage over other fungi in moist conditions with high carbon dioxide levels, such as inside a roquefort cheese or in gas tight grain storage. The key to success in food packaging is to recognise the food ecosystem, as it enables us to identify which micro...

  3. Host-pathogen interactions between the human innate immune system and Candida albicans-understanding and modeling defense and evasion strategies.

    Science.gov (United States)

    Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F; Dandekar, Thomas; Schuster, Stefan

    2015-01-01

    The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given.

  4. Hospitalized Patients and Fungal Infections

    Science.gov (United States)

    ... These types of infections are called healthcare-associated infections (HAIs). Hospital staff and healthcare providers do everything they can ... IV tube) can increase your risk for fungal infection. During your hospital stay you may need a central venous catheter, ...

  5. Fungal Entomopathogens in the Rhizosphere

    Science.gov (United States)

    Entomopathogenic fungi are found in a wide variety of fungal groups. The order Hypocreales contains the largest number of entomogenous fungi, including two of the most widely studied, Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae) and Metarhizium anisopliae (Metchnikoff) Sorok...

  6. Chronic invasive fungal rhinosinusitis by Paecilomyces variotii: A rare case report.

    Science.gov (United States)

    Swami, T; Pannu, S; Kumar, Mukesh; Gupta, G

    2016-01-01

    Fungal infection of the paranasal sinuses is an increasingly recognised entity, both in normal and immunocompromised individuals. The recent increase in mycotic nasal and paranasal infections is due to both improved diagnostic research and an increase in the conditions that favour fungal infection. Aspergillus, Candida, and Mucor species are the most common causative agents of fungal sinusitis, but infection with lesser known species have been reported across the world infrequently. This article reviews and presents a case report of chronic fungal sinusitis in an immunocompetent adult male infected with Paecilomyces variotii which is opportunistic soil saprophyte, uncommon to humans.

  7. Chronic invasive fungal rhinosinusitis by Paecilomyces variotii: A rare case report

    Directory of Open Access Journals (Sweden)

    T Swami

    2016-01-01

    Full Text Available Fungal infection of the paranasal sinuses is an increasingly recognised entity, both in normal and immunocompromised individuals. The recent increase in mycotic nasal and paranasal infections is due to both improved diagnostic research and an increase in the conditions that favour fungal infection. Aspergillus, Candida, and Mucor species are the most common causative agents of fungal sinusitis, but infection with lesser known species have been reported across the world infrequently. This article reviews and presents a case report of chronic fungal sinusitis in an immunocompetent adult male infected with Paecilomyces variotii which is opportunistic soil saprophyte, uncommon to humans.

  8. Integrated Human Futures Modeling in Egypt

    Energy Technology Data Exchange (ETDEWEB)

    Passell, Howard D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Aamir, Munaf Syed [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bernard, Michael Lewis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Beyeler, Walter E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Fellner, Karen Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hayden, Nancy Kay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jeffers, Robert Fredric [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Keller, Elizabeth James Kistin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Malczynski, Leonard A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mitchell, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Silver, Emily [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tidwell, Vincent C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Villa, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Vugrin, Eric D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Engelke, Peter [Atlantic Council, Washington, D.C. (United States); Burrow, Mat [Atlantic Council, Washington, D.C. (United States); Keith, Bruce [United States Military Academy, West Point, NY (United States)

    2016-01-01

    The Integrated Human Futures Project provides a set of analytical and quantitative modeling and simulation tools that help explore the links among human social, economic, and ecological conditions, human resilience, conflict, and peace, and allows users to simulate tradeoffs and consequences associated with different future development and mitigation scenarios. In the current study, we integrate five distinct modeling platforms to simulate the potential risk of social unrest in Egypt resulting from the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile in Ethiopia. The five platforms simulate hydrology, agriculture, economy, human ecology, and human psychology/behavior, and show how impacts derived from development initiatives in one sector (e.g., hydrology) might ripple through to affect other sectors and how development and security concerns may be triggered across the region. This approach evaluates potential consequences, intended and unintended, associated with strategic policy actions that span the development-security nexus at the national, regional, and international levels. Model results are not intended to provide explicit predictions, but rather to provide system-level insight for policy makers into the dynamics among these interacting sectors, and to demonstrate an approach to evaluating short- and long-term policy trade-offs across different policy domains and stakeholders. The GERD project is critical to government-planned development efforts in Ethiopia but is expected to reduce downstream freshwater availability in the Nile Basin, fueling fears of negative social and economic impacts that could threaten stability and security in Egypt. We tested these hypotheses and came to the following preliminary conclusions. First, the GERD will have an important short-term impact on water availability, food production, and hydropower production in Egypt, depending on the short- term reservoir fill rate. Second, the GERD will have a very small impact on

  9. Modulation of innate and antigen-specific immune functions directed against Listeria monocytogenes by fungal toxins in vitro.

    Science.gov (United States)

    Herter, I; Geginat, G; Hof, H; Kupfahl, C

    2014-05-01

    Mycotoxins, a large group of secondary fungal metabolites, are ubiquitously present in the environment and are potentially harmful to exposed humans and animals. Despite increasing interest in this group of fungal metabolites it is still difficult to estimate the relative toxic potential of one individual mycotoxin compared with others. We therefore compared the effects of some of the most important mycotoxins on effector cells of the innate and adaptive immune system in an in vitro model. Our data show clear differences of various mycotoxins in regard of their immunotoxic potential on mouse macrophages and T cells. Our results also indicate differences in the susceptibility of specific immune effector functions of macrophages and T cells exposed to mycotoxins. Thus, our results enhance the understanding of role of mycotoxins in the pathogenesis of human and animal diseases.

  10. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  11. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis

    Science.gov (United States)

    Averette, Anna F.; Lee, Soo Chan; Kim, Taeyup; Bahn, Yong-Sun; Robbins, Nicole; Heitman, Joseph; Cowen, Leah E.

    2016-01-01

    Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation

  12. Genomic responses in mouse models poorly mimic human inflammatory diseases.

    Science.gov (United States)

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

  13. Genomic responses in mouse models poorly mimic human inflammatory diseases

    Science.gov (United States)

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  14. Modeling bursts and heavy tails in human dynamics

    OpenAIRE

    Vazquez, A.; Oliveira, J. Gama; Dezso, Z.; Goh, K. -I.; Kondor, I.; Barabasi, A. -L.

    2005-01-01

    Current models of human dynamics, used from risk assessment to communications, assume that human actions are randomly distributed in time and thus well approximated by Poisson processes. We provide direct evidence that for five human activity patterns the timing of individual human actions follow non-Poisson statistics, characterized by bursts of rapidly occurring events separated by long periods of inactivity. We show that the bursty nature of human behavior is a consequence of a decision ba...

  15. Hsp90 governs dispersion and drug resistance of fungal biofilms.

    Directory of Open Access Journals (Sweden)

    Nicole Robbins

    2011-09-01

    Full Text Available Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving

  16. Sebacinales everywhere: previously overlooked ubiquitous fungal endophytes.

    Science.gov (United States)

    Weiss, Michael; Sýkorová, Zuzana; Garnica, Sigisfredo; Riess, Kai; Martos, Florent; Krause, Cornelia; Oberwinkler, Franz; Bauer, Robert; Redecker, Dirk

    2011-02-15

    Inconspicuous basidiomycetes from the order Sebacinales are known to be involved in a puzzling variety of mutualistic plant-fungal symbioses (mycorrhizae), which presumably involve transport of mineral nutrients. Recently a few members of this fungal order not fitting this definition and commonly referred to as 'endophytes' have raised considerable interest by their ability to enhance plant growth and to increase resistance of their host plants against abiotic stress factors and fungal pathogens. Using DNA-based detection and electron microscopy, we show that Sebacinales are not only extremely versatile in their mycorrhizal associations, but are also almost universally present as symptomless endophytes. They occurred in field specimens of bryophytes, pteridophytes and all families of herbaceous angiosperms we investigated, including liverworts, wheat, maize, and the non-mycorrhizal model plant Arabidopsis thaliana. They were present in all habitats we studied on four continents. We even detected these fungi in herbarium specimens originating from pioneering field trips to North Africa in the 1830s/40s. No geographical or host patterns were detected. Our data suggest that the multitude of mycorrhizal interactions in Sebacinales may have arisen from an ancestral endophytic habit by specialization. Considering their proven beneficial influence on plant growth and their ubiquity, endophytic Sebacinales may be a previously unrecognized universal hidden force in plant ecosystems.

  17. Sebacinales everywhere: previously overlooked ubiquitous fungal endophytes.

    Directory of Open Access Journals (Sweden)

    Michael Weiss

    Full Text Available Inconspicuous basidiomycetes from the order Sebacinales are known to be involved in a puzzling variety of mutualistic plant-fungal symbioses (mycorrhizae, which presumably involve transport of mineral nutrients. Recently a few members of this fungal order not fitting this definition and commonly referred to as 'endophytes' have raised considerable interest by their ability to enhance plant growth and to increase resistance of their host plants against abiotic stress factors and fungal pathogens. Using DNA-based detection and electron microscopy, we show that Sebacinales are not only extremely versatile in their mycorrhizal associations, but are also almost universally present as symptomless endophytes. They occurred in field specimens of bryophytes, pteridophytes and all families of herbaceous angiosperms we investigated, including liverworts, wheat, maize, and the non-mycorrhizal model plant Arabidopsis thaliana. They were present in all habitats we studied on four continents. We even detected these fungi in herbarium specimens originating from pioneering field trips to North Africa in the 1830s/40s. No geographical or host patterns were detected. Our data suggest that the multitude of mycorrhizal interactions in Sebacinales may have arisen from an ancestral endophytic habit by specialization. Considering their proven beneficial influence on plant growth and their ubiquity, endophytic Sebacinales may be a previously unrecognized universal hidden force in plant ecosystems.

  18. Functional analysis of fungal polyketide biosynthesis genes.

    Science.gov (United States)

    Fujii, Isao

    2010-05-01

    Fungal polyketides have huge structural diversity from simple aromatics to highly modified complex reduced-type compounds. Despite such diversty, single modular iterative type I polyketide synthases (iPKSs) are responsible for their carbon skeleton construction. Using heterologous expression systems, we have studied on ATX, a 6-methylsalicylic acid synthase from Aspergillus terreus as a model iPKS. In addition, iPKS functions involved in fungal spore pigment biosynthesis were analyzed together with polyketide-shortening enzymes that convert products of PKSs to shorter ketides by hydrolytic C-C bond cleavage. In our studies on reducing-type iPKSs, we cloned and expressed PKS genes, pksN, pksF, pksK and sol1 from Alternaria solani. The sol gene cluster was found to be involved in solanapyrone biosynthesis and sol5 was identified to encode solanapyrone synthase, a Diels-Alder enzyme. Our fungal PKS studies were further extended to identify the function of PKS-nonribosomal peptide synthase involved in cyclopiazonic acid biosynthesis.

  19. Host-pathogen interactions between the human innate immune system and Candida albicans - Understanding and modeling defense and evasion strategies

    Directory of Open Access Journals (Sweden)

    Sybille eDühring

    2015-06-01

    Full Text Available The diploid, polymorphic yeast Candida albicans is one of the most important humanpathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within thehuman host for a long time. Alterations in the host environment, however, can render C. albicansvirulent. In this review, we describe the immunological cross-talk between C. albicans and thehuman innate immune system. We give an overview in form of pairs of human defense strategiesincluding immunological mechanisms as well as general stressors such as nutrient limitation,pH, fever etc. and the corresponding fungal response and evasion mechanisms. FurthermoreComputational Systems Biology approaches to model and investigate these complex interactionare highlighted with a special focus on game-theoretical methods and agent-based models. Anoutlook on interesting questions to be tackled by Systems Biology regarding entangled defenseand evasion mechanisms is given.

  20. Modeling human response errors in synthetic flight simulator domain

    Science.gov (United States)

    Ntuen, Celestine A.

    1992-01-01

    This paper presents a control theoretic approach to modeling human response errors (HRE) in the flight simulation domain. The human pilot is modeled as a supervisor of a highly automated system. The synthesis uses the theory of optimal control pilot modeling for integrating the pilot's observation error and the error due to the simulation model (experimental error). Methods for solving the HRE problem are suggested. Experimental verification of the models will be tested in a flight quality handling simulation.

  1. A long term model of circulation. [human body

    Science.gov (United States)

    White, R. J.

    1974-01-01

    A quantitative approach to modeling human physiological function, with a view toward ultimate application to long duration space flight experiments, was undertaken. Data was obtained on the effect of weightlessness on certain aspects of human physiological function during 1-3 month periods. Modifications in the Guyton model are reviewed. Design considerations for bilateral interface models are discussed. Construction of a functioning whole body model was studied, as well as the testing of the model versus available data.

  2. Competency Modeling in Extension Education: Integrating an Academic Extension Education Model with an Extension Human Resource Management Model

    Science.gov (United States)

    Scheer, Scott D.; Cochran, Graham R.; Harder, Amy; Place, Nick T.

    2011-01-01

    The purpose of this study was to compare and contrast an academic extension education model with an Extension human resource management model. The academic model of 19 competencies was similar across the 22 competencies of the Extension human resource management model. There were seven unique competencies for the human resource management model.…

  3. Fungal-Fungal Interactions in Leaf-Cutting Ant Agriculture

    Directory of Open Access Journals (Sweden)

    Sunshine A. Van Bael

    2011-01-01

    Full Text Available Many organisms participate in symbiotic relationships with other organisms, yet studies of symbioses typically have focused on the reciprocal costs and benefits within a particular host-symbiont pair. Recent studies indicate that many ecological interactions involve alliances of symbionts acting together as mutualistic consortia against other consortia. Such interacting consortia are likely to be widespread in nature, even if the interactions often occur in a cryptic fashion. Little theory and empirical data exist concerning how these complex interactions shape ecological outcomes in nature. Here, we review recent work on fungal-fungal interactions between two consortia: (i leaf-cutting ants and their symbiotic fungi (the latter grown as a food crop by the former and (ii tropical plants and their foliar endophytes (the cryptic symbiotic fungi within leaves of the former. Plant characteristics (e.g., secondary compounds or leaf physical properties of leaves are involved in leaf-cutting ant preferences, and a synthesis of published information suggests that these plant traits could be modified by fungal presence. We discuss potential mechanisms for how fungal-fungal interactions proceed in the leaf-cutting ant agriculture and suggest themes for future research.

  4. Characteristics and determinants of ambient fungal spores in Hualien, Taiwan

    Science.gov (United States)

    Ho, Hsiao-Man; Rao, Carol Y.; Hsu, Hsiao-Hsien; Chiu, Yueh-Hsiu; Liu, Chi-Ming; Chao, H. Jasmine

    Characteristics and determinants of ambient aeroallergens are of much concern in recent years because of the apparent health impacts of allergens. Yet relatively little is known about the complex behaviors of ambient aeroallergens. To address this issue, we monitored ambient fungal spores in Hualien, Taiwan from 1993-1996 to examine the compositions and temporal variations of fungi, and to evaluate possible determinants. We used a Burkard seven-day volumetric spore trap to collect daily fungal spores. Air pollutants, meteorological factors, and Asian dust events were included in the statistical analyses to predict fungal levels. We found that the most dominant fungal categories were ascospores, followed by Cladosporium and Aspergillus/Penicillium. The majority of the fungal categories had significant diurnal and seasonal variations. Total fungi, Cladosporium, Ganoderma, Arthrinium/Papularia, Cercospora, Periconia, Alternaria, Botrytis, and PM 10 had significantly higher concentrations ( p<0.05) during the period affected by Asian dust events. In multiple regression models, we found that temperature was consistently and positively associated with fungal concentrations. Other factors correlated with fungal concentrations included ozone, particulate matters with an aerodynamic diameter less than 10 μm (PM 10), relative humidity, rainfall, atmospheric pressure, total hydrocarbons, carbon monoxide, nitrogen dioxide, and sulfur dioxide. Most of the fungal categories had higher levels in 1994 than in 1995-96, probably due to urbanization of the study area. In this study, we demonstrated complicated interrelationships between fungi and air pollution/meteorological factors. In addition, long-range transport of air pollutants contributed significantly to local aeroallergen levels. Future studies should examine the health impacts of aeroallergens, as well as the synergistic/antagonistic effects of weather, and local and global-scale air pollutions.

  5. Bioactivities of Ketones Terpenes: Antifungal Effect on F. verticillioides and Repellents to Control Insect Fungal Vector, S. zeamais

    Directory of Open Access Journals (Sweden)

    Romina P. Pizzolitto

    2015-11-01

    Full Text Available Maize is one the most important staple foods in the world. However, numerous pests, such as fungal pathogens, e.g., Fusarium verticillioides, and insects, such as Sitophlilus zeamais, attack maize grains during storage. Many F. verticillioides strains produce fumonisins, one of the most important mycotoxin that causes toxic effects on human and animal health. This situation is aggravated by the insect fungal vector, Sitophlilus zeamais, which contributes to the dispersal of fungal spores, and through feeding damage, provide entry points for fungal infections. The aim of this study was to evaluate in vitro bioassays, the antifungal activity on F. verticillioides M3125 and repellent effects against S. zeamais of ketone terpenes. In addition, we performed Quantitative structure–activity relationship (Q-SAR studies between physico-chemical properties of ketone terpenes and the antifungal effect. Thymoquinone was the most active compound against F. verticillioides (Minimum Inhibitory Concentration, MIC: 0.87 affecting the lag phase and the growth rate showing a total inhibition of growth at concentration higher than 2 mM (p < 0.05. The Q-SAR model revealed that the antifungal activity of ketone compounds is related to the electronic descriptor, Pi energy. Thymoquinone showed a strong repellent effect (−77.8 ± 8.5, p < 0.001 against S. zeamais. These findings make an important contribution to the search for new compounds to control two stored pests of maize.

  6. Climate Controls AM Fungal Distributions from Global to Local Scales

    Science.gov (United States)

    Kivlin, S. N.; Hawkes, C.; Muscarella, R.; Treseder, K. K.; Kazenel, M.; Lynn, J.; Rudgers, J.

    2016-12-01

    Arbuscular mycorrhizal (AM) fungi have key functions in terrestrial biogeochemical processes; thus, determining the relative importance of climate, edaphic factors, and plant community composition on their geographic distributions can improve predictions of their sensitivity to global change. Local adaptation by AM fungi to plant hosts, soil nutrients, and climate suggests that all of these factors may control fungal geographic distributions, but their relative importance is unknown. We created species distribution models for 142 AM fungal taxa at the global scale with data from GenBank. We compared climate variables (BioClim and soil moisture), edaphic variables (phosphorus, carbon, pH, and clay content), and plant variables using model selection on models with (1) all variables, (2) climatic variables only (including soil moisture) and (3) resource-related variables only (all other soil parameters and NPP) using the MaxEnt algorithm evaluated with ENMEval. We also evaluated whether drivers of AM fungal distributions were phylogenetically conserved. To test whether global correlates of AM fungal distributions were reflected at local scales, we then surveyed AM fungi in nine plant hosts along three elevation gradients in the Upper Gunnison Basin, Colorado, USA. At the global scale, the distributions of 55% of AM fungal taxa were affected by both climate and soil resources, whereas 16% were only affected by climate and 29% were only affected by soil resources. Even for AM fungi that were affected by both climate and resources, the effects of climatic variables nearly always outweighed those of resources. Soil moisture and isothermality were the main climatic and NPP and soil carbon the main resource related factors influencing AM fungal distributions. Distributions of closely related AM fungal taxa were similarly affected by climate, but not by resources. Local scale surveys of AM fungi across elevations confirmed that climate was a key driver of AM fungal

  7. On our best behavior: optimality models in human behavioral ecology.

    Science.gov (United States)

    Driscoll, Catherine

    2009-06-01

    This paper discusses problems associated with the use of optimality models in human behavioral ecology. Optimality models are used in both human and non-human animal behavioral ecology to test hypotheses about the conditions generating and maintaining behavioral strategies in populations via natural selection. The way optimality models are currently used in behavioral ecology faces significant problems, which are exacerbated by employing the so-called 'phenotypic gambit': that is, the bet that the psychological and inheritance mechanisms responsible for behavioral strategies will be straightforward. I argue that each of several different possible ways we might interpret how optimality models are being used for humans face similar and additional problems. I suggest some ways in which human behavioral ecologists might adjust how they employ optimality models; in particular, I urge the abandonment of the phenotypic gambit in the human case.

  8. Diffusion Based Modeling of Human Brain Response to External Stimuli

    CERN Document Server

    Namazi, Hamidreza

    2012-01-01

    Human brain response is the overall ability of the brain in analyzing internal and external stimuli in the form of transferred energy to the mind/brain phase-space and thus, making the proper decisions. During the last decade scientists discovered about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research there was less effort which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling of human EEG signal, as an alert state of overall human brain activity monitoring, due to receiving external stimuli, based on fractional diffusion equation. The results of this modeling show very good agreement with the real human EEG signal and thus, this model can be used as a strong representative of the human brain activity.

  9. Neglected fungal zoonoses: Hidden threats to man and animals

    NARCIS (Netherlands)

    S. Seyedmousavi (Seyedmojtaba); J. Guillot; A. Tolooe (Ali); P.E. Verweij (Paul); G.S. de Hoog

    2015-01-01

    textabstractZoonotic fungi can be naturally transmitted between animals and humans, and in some cases cause significant public health problems. A number of mycoses associated with zoonotic transmission are among the group of the most common fungal diseases, worldwide. It is, however, notable that so

  10. Germination inhibitors of fungal spores: identification and mode of action

    NARCIS (Netherlands)

    Chitarra, G.S.

    2003-01-01

    Fungi can be found in a wide variety of environments, such as seeds, plants, soil, water, insects, and food products. Fungi and their toxic metabolites cause losses of food products, and diseases in plants and animals, and may have adverse effects on human health. A crucial step in fungal

  11. Characterizations of atmospheric fungal aerosol in Beijing, China

    Science.gov (United States)

    Liang, Linlin; Engling, Guenter; He, Kebin; Du, Zhenyu

    2013-04-01

    Fungal aerosols constitute the most abundant fraction of biological aerosols in the atmosphere, influencing human health, the biosphere, atmospheric chemistry and climate. However, the total abundance of fungal spores in the atmosphere is still poorly understood and quantified. PM10 and PM2.5 samples were collected by high volume samplers simultaneously at a rural site (MY) and an urban site (THU) in Beijing, China. Various carbohydrates were quantified by high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD), including the sugar alcohols mannitol and arabitol, proposed as molecular tracers for fungal aerosol. The annual average concentrations of arabitol in PM2.5 and PM10 at the THU site were 7.4±9.4 ng/m3 and 10.3±9.5 ng/m3, and the respective mannitol concentrations were 21.0±20.4 ng/m3 and 31.9±26.9 ng/m3. Compared to PM10, the monthly average concentrations of arabitol and mannitol in PM2.5 did not vary significantly and were present at nearly consistent levels in the different seasons. Moreover, during summer and autumn higher arabitol and mannitol levels than during spring and winter were observed in coarse particles, probably due to different dominant sources of fungal spores in different seasons. In the dry period (i.e., winter and spring) in Beijing, probably only the suspension from exposed surfaces, (e.g., soil resuspension, transported dust, etc.) can be regarded as the main sources for fungal aerosols. On the other hand, in summer and autumn, fungal spores in the atmosphere can be derived from more complex sources, including plants, vegetation decomposition and agricultural activity, such as ploughing; these fungal spore sources may contribute more to coarse PM. Mannitol and arabitol correlated well with each other, both in PM10 (R2 = 0.71) and PM2.5 (R2 = 0.81). Although fungal spore levels at rural sites were consistently higher than those at urban sites in other studies, the findings in our study were

  12. DemaDb: an integrated dematiaceous fungal genomes database.

    Science.gov (United States)

    Kuan, Chee Sian; Yew, Su Mei; Chan, Chai Ling; Toh, Yue Fen; Lee, Kok Wei; Cheong, Wei-Hien; Yee, Wai-Yan; Hoh, Chee-Choong; Yap, Soon-Joo; Ng, Kee Peng

    2016-01-01

    Many species of dematiaceous fungi are associated with allergic reactions and potentially fatal diseases in human, especially in tropical climates. Over the past 10 years, we have isolated more than 400 dematiaceous fungi from various clinical samples. In this study, DemaDb, an integrated database was designed to support the integration and analysis of dematiaceous fungal genomes. A total of 92 072 putative genes and 6527 pathways that identified in eight dematiaceous fungi (Bipolaris papendorfii UM 226, Daldinia eschscholtzii UM 1400, D. eschscholtzii UM 1020, Pyrenochaeta unguis-hominis UM 256, Ochroconis mirabilis UM 578, Cladosporium sphaerospermum UM 843, Herpotrichiellaceae sp. UM 238 and Pleosporales sp. UM 1110) were deposited in DemaDb. DemaDb includes functional annotations for all predicted gene models in all genomes, such as Gene Ontology, EuKaryotic Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes (KEGG), Pfam and InterProScan. All predicted protein models were further functionally annotated to Carbohydrate-Active enzymes, peptidases, secondary metabolites and virulence factors. DemaDb Genome Browser enables users to browse and visualize entire genomes with annotation data including gene prediction, structure, orientation and custom feature tracks. The Pathway Browser based on the KEGG pathway database allows users to look into molecular interaction and reaction networks for all KEGG annotated genes. The availability of downloadable files containing assembly, nucleic acid, as well as protein data allows the direct retrieval for further downstream works. DemaDb is a useful resource for fungal research community especially those involved in genome-scale analysis, functional genomics, genetics and disease studies of dematiaceous fungi. Database URL: http://fungaldb.um.edu.my.

  13. Microbiological diagnostics of fungal infections

    Directory of Open Access Journals (Sweden)

    Corrado Girmenia

    2013-07-01

    Full Text Available Laboratory tests for the detection of fungal infections are easy to perform. The main obstacle to a correct diagnosis is the correlation between the laboratory findings and the clinical diagnosis. Among pediatric patients, the most common fungal pathogen is Candida. The detection of fungal colonization may be performed through the use of chromogenic culture media, which allows also the identification of Candida subspecies, from which pathogenicity depends. In neonatology, thistest often drives the decision to begin a empiric therapy; in this regard, a close cooperation between microbiologists and clinicians is highly recommended. Blood culture, if positive, is a strong confirmation of fungal infection; however, its low sensitivity results in a high percentage of false negatives, thus decreasing its reliability. Molecular diagnostics is still under evaluation, whereas the detection of some fungal antigens, such as β-D-glucan, galactomannan, mannoprotein, and cryptococcal antigen in the serum is used for adults, but still under evaluations for pediatric patients.http://dx.doi.org/10.7175/rhc.v4i1S.862

  14. Modelling Human Emotions for Tactical Decision-Making Games

    Science.gov (United States)

    Visschedijk, Gillian C.; Lazonder, Ard W.; van der Hulst, Anja; Vink, Nathalie; Leemkuil, Henny

    2013-01-01

    The training of tactical decision making increasingly occurs through serious computer games. A challenging aspect of designing such games is the modelling of human emotions. Two studies were performed to investigate the relation between fidelity and human emotion recognition in virtual human characters. Study 1 compared five versions of a virtual…

  15. Modelling human emotions for tactical decision-making games

    NARCIS (Netherlands)

    Visschedijk, G.C.; Lazonder, A.W.; Hulst, A.H. van der; Vink, N.; Leemkuil, H.

    2013-01-01

    The training of tactical decision making increasingly occurs through serious computer games. A challenging aspect of designing such games is the modelling of human emotions. Two studieswere performed to investigate the relation between fidelity and human emotion recognition in virtual human characte

  16. Modelling human emotions for tactical decision-making games

    NARCIS (Netherlands)

    Visschedijk, G.C.; Lazonder, A.W.; Hulst, A.H. van der; Vink, N.; Leemkuil, H.

    2013-01-01

    The training of tactical decision making increasingly occurs through serious computer games. A challenging aspect of designing such games is the modelling of human emotions. Two studieswere performed to investigate the relation between fidelity and human emotion recognition in virtual human characte

  17. The Spectrum of Fungi That Infects Humans

    Science.gov (United States)

    Köhler, Julia R.; Casadevall, Arturo; Perfect, John

    2015-01-01

    Few among the millions of fungal species fulfill four basic conditions necessary to infect humans: high temperature tolerance, ability to invade the human host, lysis and absorption of human tissue, and resistance to the human immune system. In previously healthy individuals, invasive fungal disease is rare because animals’ sophisticated immune systems evolved in constant response to fungal challenges. In contrast, fungal diseases occur frequently in immunocompromised patients. Paradoxically, successes of modern medicine have put increasing numbers of patients at risk for invasive fungal infections. Uncontrolled HIV infection additionally makes millions vulnerable to lethal fungal diseases. A concerted scientific and social effort is needed to meet these challenges. PMID:25367975

  18. Research on Dynamic Model of the Human Body

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chun-lin; WANG Guang-quan; LU Dun-yong

    2005-01-01

    After summarizing the current situation of the research on human body modeling, a new dynamic model containing 5 equivalent masses has been proposed and the corresponding dynamic equations has been deduced too. By using this new model, more detailed information about the situation of the human body under impact and vibration can be obtained. The new model solves the problem that transmission functions of forces inside the human body can't be deduced by using 3-equivalent-mass model. It will find its usage in many applications.

  19. Potential of small-molecule fungal metabolites in antiviral chemotherapy.

    Science.gov (United States)

    Roy, Biswajit G

    2017-08-01

    Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.

  20. Modelling Human Exposure to Chemicals in Food

    NARCIS (Netherlands)

    Slob W

    1993-01-01

    Exposure to foodborne chemicals is often estimated using the average consumption pattern in the human population. To protect the human population instead of the average individual, however, interindividual variability in consumption behaviour must be taken into account. This report shows how food

  1. Neglected fungal zoonoses: hidden threats to man and animals.

    Science.gov (United States)

    Seyedmousavi, S; Guillot, J; Tolooe, A; Verweij, P E; de Hoog, G S

    2015-05-01

    Zoonotic fungi can be naturally transmitted between animals and humans, and in some cases cause significant public health problems. A number of mycoses associated with zoonotic transmission are among the group of the most common fungal diseases, worldwide. It is, however, notable that some fungal diseases with zoonotic potential have lacked adequate attention in international public health efforts, leading to insufficient attention on their preventive strategies. This review aims to highlight some mycoses whose zoonotic potential received less attention, including infections caused by Talaromyces (Penicillium) marneffei, Lacazia loboi, Emmonsia spp., Basidiobolus ranarum, Conidiobolus spp. and Paracoccidioides brasiliensis.

  2. Dynamics of the two process model of human sleep regulation

    Science.gov (United States)

    Kenngott, Max; McKay, Cavendish

    2011-04-01

    We examine the dynamics of the two process model of human sleep regulation. In this model, sleep propensity is governed by the interaction between a periodic threshold (process C) and a saturating growth/decay (process S). We find that the parameter space of this model admits sleep cycles with a wide variety of characteristics, many of which are not observed in normal human sleepers. We also examine the effects of phase dependent feedback on this model.

  3. Minimizing Human Risk: Human Performance Models in the Space Human Factors and Habitability and Behavioral Health and Performance Elements

    Science.gov (United States)

    Gore, Brian F.

    2016-01-01

    Human space exploration has never been more exciting than it is today. Human presence to outer worlds is becoming a reality as humans are leveraging much of our prior knowledge to the new mission of going to Mars. Exploring the solar system at greater distances from Earth than ever before will possess some unique challenges, which can be overcome thanks to the advances in modeling and simulation technologies. The National Aeronautics and Space Administration (NASA) is at the forefront of exploring our solar system. NASA's Human Research Program (HRP) focuses on discovering the best methods and technologies that support safe and productive human space travel in the extreme and harsh space environment. HRP uses various methods and approaches to answer questions about the impact of long duration missions on the human in space including: gravity's impact on the human body, isolation and confinement on the human, hostile environments impact on the human, space radiation, and how the distance is likely to impact the human. Predictive models are included in the HRP research portfolio as these models provide valuable insights into human-system operations. This paper will provide an overview of NASA's HRP and will present a number of projects that have used modeling and simulation to provide insights into human-system issues (e.g. automation, habitat design, schedules) in anticipation of space exploration.

  4. Numerical Modeling of Electromagnetic Field Effects on the Human Body

    Directory of Open Access Journals (Sweden)

    Zuzana Psenakova

    2006-01-01

    Full Text Available Interactions of electromagnetic field (EMF with environment and with tissue of human beings are still under discussion and many research teams are investigating it. The human simulation models are used for biomedical research in a lot of areas, where it is advantage to replace real human body (tissue by the numerical model. Biological effects of EMF are one of the areas, where numerical models are used with many advantages. On the other side, this research is very specific and it is always quite hard to simulate realistic human tissue. This paper deals with different possibilities of numerical modelling of electromagnetic field effects on the human body (especially calculation of the specific absorption rate (SAR distribution in human body and thermal effect.

  5. Pharmacological migraine provocation: a human model of migraine

    DEFF Research Database (Denmark)

    Ashina, Messoud; Hansen, Jakob Møller

    2010-01-01

    for migraine mechanisms. So far, however, animal models cannot predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model....... If a naturally occurring substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed...

  6. Predicting human walking gaits with a simple planar model.

    Science.gov (United States)

    Martin, Anne E; Schmiedeler, James P

    2014-04-11

    Models of human walking with moderate complexity have the potential to accurately capture both joint kinematics and whole body energetics, thereby offering more simultaneous information than very simple models and less computational cost than very complex models. This work examines four- and six-link planar biped models with knees and rigid circular feet. The two differ in that the six-link model includes ankle joints. Stable periodic walking gaits are generated for both models using a hybrid zero dynamics-based control approach. To establish a baseline of how well the models can approximate normal human walking, gaits were optimized to match experimental human walking data, ranging in speed from very slow to very fast. The six-link model well matched the experimental step length, speed, and mean absolute power, while the four-link model did not, indicating that ankle work is a critical element in human walking models of this type. Beyond simply matching human data, the six-link model can be used in an optimization framework to predict normal human walking using a torque-squared objective function. The model well predicted experimental step length, joint motions, and mean absolute power over the full range of speeds.

  7. Fungal infection following renal transplantation.

    Science.gov (United States)

    Gallis, H A; Berman, R A; Cate, T R; Hamilton, J D; Gunnells, J C; Stickel, D L

    1975-09-01

    Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

  8. Multi-agent Model of Trust in a Human Game

    NARCIS (Netherlands)

    Jonker, C.M.; Meijer, S.A.; Tykhonov, D.; Verwaart, D.

    2006-01-01

    Individual-level trust is formalized within the context of a multi-agent system that models human behaviour with respect to trust in the Trust and Tracing Game. This is a trade game on commodity supply chains and networks, designed as a reserach tool and to be played by human players. The model of t

  9. Fuzzy Control Strategies in Human Operator and Sport Modeling

    CERN Document Server

    Ivancevic, Tijana T; Markovic, Sasa

    2009-01-01

    The motivation behind mathematically modeling the human operator is to help explain the response characteristics of the complex dynamical system including the human manual controller. In this paper, we present two different fuzzy logic strategies for human operator and sport modeling: fixed fuzzy-logic inference control and adaptive fuzzy-logic control, including neuro-fuzzy-fractal control. As an application of the presented fuzzy strategies, we present a fuzzy-control based tennis simulator.

  10. An integrated model of human-wildlife interdependence

    Science.gov (United States)

    John, Kun H.; Walsh, Richard G.; Johnson, R. L.

    1994-01-01

    This paper attempts to integrate wildlife-related ecologic and economic variables into an econometric model. The model reveals empirical evidence of the presumed interdependence of human-wildlife and the holistic nature of humanity's relationship to the ecosystem. Human use of biologic resources varies not only with income, education, and population, but also with sustainability of humankind's action relative to the quality and quantity of the supporting ecological base.

  11. Scytalidium dimidiatum associated invasive fungal sinusitis in an immunocompetent patient.

    Science.gov (United States)

    Hariri, A; Choudhury, N; Saleh, H A

    2014-11-01

    Scytalidium dimidiatum is a soil and plant pathogen that frequently affects fruit trees, but can also cause human infection. There are only two reported cases of invasive fungal sinusitis involving this rare micro-organism. This paper reports the first case of invasive fungal sinusitis caused by Scytalidium dimidiatum occurring in a young immunocompetent patient from a non-endemic region, and discusses potential sources of exposure and relevance of local factors. Case report. The patient was treated successfully with a combination of functional endoscopic sinus surgery, and antifungal and corticosteroid treatment. This paper describes the first reported case of invasive fungal sinusitis secondary to Scytalidium dimidiatum in a young immunocompetent patient from a non-endemic region. Importance is placed on following a systematic process of investigation and management, and adhering to well-defined basic surgical principles.

  12. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

    Science.gov (United States)

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

    2017-06-01

    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4(+) T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment.

  13. Pearls and pitfalls in human pharmacological models of migraine

    DEFF Research Database (Denmark)

    Ashina, Messoud; Hansen, Jakob Møller; Olesen, Jes

    2013-01-01

    In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of new possible anti-migraine agents. In vivo animal models enable the study of vascular responses, neurogenic inflammation, peptide release and genetic predisposition and thus...... have provided leads in the search for migraine mechanisms. All animal-based results must, however, be validated in human studies because so far no animal models can predict the efficacy of new therapies for migraine. Given the nature of migraine attacks, fully reversible and treatable, the headache....... To this end, a human in vivo model of experimental headache and migraine in humans has been developed. Human models of migraine offer unique possibilities to study mechanisms responsible for migraine and to explore the mechanisms of action of existing and future anti-migraine drugs. The human model has played...

  14. Fungal laryngitis in immunocompetent patients.

    Science.gov (United States)

    Ravikumar, A; Prasanna Kumar, S; Somu, L; Sudhir, B

    2014-01-01

    The diagnosis of fungal laryngitis is often overlooked in immunocompetent patients because it is commonly considered a disease of the immunocompromised. Further confusion is caused by clinical and histological similarity to more common conditions like Leukoplakia. Demonstration of hyperkeratosis particularly if associated with intraepithelial neutrophils on biopsy should trigger a search for fungus using specialized stains. These patients usually present with hoarseness of voice. Pain is present inconsistently along with dysphagia and odynophagia. We present three cases of fungal laryngitis in immunocompetent patients out of which one underwent microlaryngeal surgery with excision biopsy. All these patients responded well with oral antifungal therapy.

  15. Splash : the dispersal of fungal plant pathogens in rain events

    NARCIS (Netherlands)

    Pielaat, A.

    2000-01-01

    Models were developed to study splash dispersal of fungal plant pathogens in space and time. The models incorporate the main mechanisms involved in splash dispersal, that is 1. A raindrop hits the thin water film on the crop surface containing spores and spores are dispersed in the splashing rain dr

  16. The Fungal Genetics Stock Center: a repository for 50 years of fungal genetics research

    Indian Academy of Sciences (India)

    K McCluskey; A Wiest; M Plamann

    2010-03-01

    The Fungal Genetics Stock Center (FGSC) was established in 1960 to ensure that important strains used in early genetics research were available to subsequent generations of fungal geneticists. Originally, only mutant strains were held. At present, any organism that has had its genome sequenced is a genetic system and so the FGSC has added many new organisms. The FGSC is well integrated in its core community and, as research came to depend on cloned genes, vectors and gene libraries, the FGSC included these materials. When the community expanded to include plant and human pathogens, the FGSC adopted these systems as well. Wild isolates from around the world have also proven instrumental in answering important questions. The FGSC holds tremendous diversity of the Neurospora species, which form the core of the collection. The growth in the number of strains distributed illustrates the growth in research on fungi. Because of its position near the centre of the fungal genetics effort, the FGSC is also the first to see trends in research directions. One recent example is the 300% jump in requests for strains of Neurospora crassa carrying a mutation that makes them sensitive to high salt concentration. These strains were seldom requested over many years, but became among our most popular resources following the demonstration of their utility in studying fungicide resistance. This exemplifies why materials need to be preserved without regard to their immediate perceived value and reinforces the need for long-term support for preservation of a broad variety of genetic resources.

  17. Mice with human immune system components as in vivo models for infections with human pathogens

    OpenAIRE

    Rämer, P C; Chijioke, O; Meixlsperger, S; Leung, C S; Münz, C.

    2011-01-01

    Many pathogens relevant to human disease do not infect other animal species. Therefore, animal models that reconstitute or harbour human tissues are explored as hosts for these. In this review, we will summarize recent advances to utilize mice with human immune system components, reconstituted from hematopoietic progenitor cells in vivo. Such mice can be used to study human pathogens that replicate in leucocytes. In addition to studying the replication of these pathogens, the reconstituted hu...

  18. Variation in calculated human exposure. Comparison of calculations with seven European human exposure models

    NARCIS (Netherlands)

    Swartjes F; ECO

    2003-01-01

    Twenty scenarios, differing with respect to land use, soil type and contaminant, formed the basis for calculating human exposure from soil contaminants with the use of models contributed by seven European countries (one model per country). Here, the human exposures to children and children

  19. Modeling Human Behaviour with Higher Order Logic: Insider Threats

    DEFF Research Database (Denmark)

    Boender, Jaap; Ivanova, Marieta Georgieva; Kammuller, Florian

    2014-01-01

    In this paper, we approach the problem of modeling the human component in technical systems with a view on the difference between the use of model and theory in sociology and computer science. One aim of this essay is to show that building of theories and models for sociology can be compared...... it to the sociological process of logical explanation. As a case study on modeling human behaviour, we present the modeling and analysis of insider threats as a Higher Order Logic theory in Isabelle/HOL. We show how each of the three step process of sociological explanation can be seen in our modeling of insider’s state...

  20. Development of risk evaluation models for critically ill patients at high risk of invasive fungal disease%危重症患者侵袭性真菌病风险评估模型临床应用进展

    Institute of Scientific and Technical Information of China (English)

    魏红霞

    2016-01-01

    Invasive fungal disease(IFD) is one of the causes leading to death in intensive care unit,and now more likely to occur in non-neutropenic critically ill patients.Early diagnosis and appropriate selection of patients at high risk of IFD to receive prophylactic antifungal therapy are of great concern.Risk factors related to IFD were established by multivariable analysis and then risk evaluation models were developed.Candida score could accurately select patients who would benefit from early antifungal treatment.Evaluation and validation of risk models for non-neutropenic critically ill patients at high risk of IFD were reviewed in this article.%侵袭性真菌病(invasive fungal disease,IFD)是导致重症监护病房患者死亡的原因之一,近年来越来越多发生于非粒细胞缺乏的危重患者,早期诊断以及准确地筛选高危患者进行预防性抗真菌治疗逐渐得到重视.应用统计学多因素分析方法确立IFD相关危险因素,并建立真菌感染风险评估模型.念珠菌评分可用于选择高危患者接受早期抗真菌治疗.该文就非粒细胞缺乏的危重患者真菌感染风险评估模型的建立及验证进行综述.

  1. Human Cancer Models Initiative | Office of Cancer Genomics

    Science.gov (United States)

    The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

  2. Human surrogate models of neuropathic pain: validity and limitations.

    Science.gov (United States)

    Binder, Andreas

    2016-02-01

    Human surrogate models of neuropathic pain in healthy subjects are used to study symptoms, signs, and the hypothesized underlying mechanisms. Although different models are available, different spontaneous and evoked symptoms and signs are inducible; 2 key questions need to be answered: are human surrogate models conceptually valid, ie, do they share the sensory phenotype of neuropathic pain states, and are they sufficiently reliable to allow consistent translational research?

  3. [Attempt at computer modeling of evolution of human society].

    Science.gov (United States)

    Levchenko, V F; Menshutkin, V V

    2009-01-01

    A model of evolution of human society and biosphere, which is based on the concepts of V. I. Vernadskii about noosphere and of L. N. Gumilev about ethnogenesis is developed and studied. The mathematical apparatus of the model is composition of finite stochastic automata. By using this model, a possibility of the global ecological crisis is demonstrated in the case of preservation of the current tendencies of interaction of the biosphere and the human civilization.

  4. Aerodynamic characteristics and respiratory deposition of fungal fragments

    Science.gov (United States)

    Cho, Seung-Hyun; Seo, Sung-Chul; Schmechel, Detlef; Grinshpun, Sergey A.; Reponen, Tiina

    The purpose of this study was to investigate the aerodynamic characteristics of fungal fragments and to estimate their respiratory deposition. Fragments and spores of three different fungal species ( Aspergillus versicolor, Penicillium melinii, and Stachybotrys chartarum) were aerosolized by the fungal spore source strength tester (FSSST). An electrical low-pressure impactor (ELPI) measured the size distribution in real-time and collected the aerosolized fungal particles simultaneously onto 12 impactor stages in the size range of 0.3-10 μm utilizing water-soluble ZEF-X10 coating of the impaction stages to prevent spore bounce. For S. chartarum, the average concentration of released fungal fragments was 380 particles cm -3, which was about 514 times higher than that of spores. A. versicolor was found to release comparable amount of spores and fragments. Microscopic analysis confirmed that S. chartarum and A. versicolor did not show any significant spore bounce, whereas the size distribution of P. melinii fragments was masked by spore bounce. Respiratory deposition was calculated using a computer-based model, LUDEP 2.07, for an adult male and a 3-month-old infant utilizing the database on the concentration and size distribution of S. chartarum and A. versicolor aerosols measured by the ELPI. Total deposition fractions for fragments and spores were 27-46% and 84-95%, respectively, showing slightly higher values in an infant than in an adult. For S. chartarum, fragments demonstrated 230-250 fold higher respiratory deposition than spores, while the number of deposited fragments and spores of A. versicolor were comparable. It was revealed that the deposition ratio (the number of deposited fragments divided by that of deposited spores) in the lower airways for an infant was 4-5 times higher than that for an adult. As fungal fragments have been shown to contain mycotoxins and antigens, further exposure assessment should include the measurement of fungal fragments for

  5. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    Science.gov (United States)

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  6. Detection of Unusual Human Activities Based on Behavior Modeling

    OpenAIRE

    Hiraishi, Kunihiko; Kobayashi, Koichi

    2014-01-01

    A type of services that require human physical actions and intelligent decision making exists in various real fields, such as nursing in hospitals and caregiving in nursing homes. In this paper, we propose new formalism for modeling human behavior in such services. Behavior models are estimated from event-logs, and can be used for analysis of human activities. We show two analysis methods: one is to detect unusual human activities that appear in event-logs, and the other is to find staffs tha...

  7. Imaging fungal infections in children

    NARCIS (Netherlands)

    Ankrah, Alfred O.; Sathekge, Mike M; Dierckx, Rudi A.J.O.; Glaudemans, Andor W.J.M.

    2016-01-01

    Fungal infections in children rarely occur, but continue to have a high morbidity and mortality despite the development of newer antifungal agents. It is essential for these infections to be diagnosed at the earliest possible stage so appropriate treatment can be initiated promptly. The addition of

  8. Microbiology of systemic fungal infections

    Directory of Open Access Journals (Sweden)

    Chakrabarti A

    2005-01-01

    Full Text Available The increased incidence of systemic fungal infections in the past two decades has been overwhelming. Earlier, it was pathogenic dimorphic fungi, which were known to cause systemic infections. However, starting from the 1960s, opportunistic fungi started causing more number of infections, especially in the immunocompromised host. More recently, newer and less common fungal agents are being increasingly associated with infection in immunosuppressed hosts. Amongst dimorphic fungi, infections due to Histoplasma capsulatum and Penicillium marneffei are increasingly reported in patients with AIDS in India. H. capsulatum is found country wide, but P. marneffei remains restricted to Manipur state. Although both varieties of C. neoformans , C. neoformans var. neoformans (serotypes A & D, and C. neoformans var. gattii (serotypes B & C are reported in India, most of the cases reported are of serotype A. Increased incidence of cryptococcosis is reported from all centers with the emergence of AIDS. Systemic infection due to species under Candida , Aspergillus and zygomycetes is widely prevalent in nosocomial setting, and outbreaks due to unusual fungi are reported occasionally from tertiary care centers. This global change in systemic fungal infections has emphasized the need to develop good diagnostic mycology laboratories in this country and to recognize this increasingly large group of potential fungal pathogens.

  9. Fungal endophyte diversity in Sarracenia

    Science.gov (United States)

    Fungal endophytes were isolated from four species of the carnivorous pitcher plant genus Sarracenia: S. minor, S. oreophila, S. purpurea, and S. psittacina. Twelve taxa of fungi, eight within the Ascomycota and four within the Basidiomycota, were identified based on PCR amplification and sequencing ...

  10. Mouse models for understanding human developmental anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1989-01-01

    The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals.

  11. (Post-)genomics approaches in fungal research

    NARCIS (Netherlands)

    Aguilar-Pontes, María Victoria; de Vries, Ronald P; Zhou, M.; van den Brink, J.

    2014-01-01

    To date, hundreds of fungal genomes have been sequenced and many more are in progress. This wealth of genomic information has provided new directions to study fungal biodiversity. However, to further dissect and understand the complicated biological mechanisms involved in fungal life styles, functio

  12. Soil Fraction and Black Carbon Particles of Amazonian Dark Earth Harbor Different Fungal Abundance and Diversity

    NARCIS (Netherlands)

    Reis Lucheta, Adriano; Souza Cannavan, F.S.; Tsai, S.M.; Kuramae, E.E.

    2017-01-01

    Amazonian Dark Earth (ADE) is a highly fertile soil of anthropogenic origin characterized by higher amount of charred black carbon (BC). ADE is considered a fertility model, however knowledge about the fungal community structure and diversity inhabiting ADE and BC is scarce. Fungal community

  13. Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis

    Science.gov (United States)

    Miller, Joe; Chi, Thomas; Kapahi, Pankaj; Kahn, Arnold J.; Kim, Man Su; Hirata, Taku; Romero, Michael F.; Dow, Julian A.T.; Stoller, Marshall L.

    2013-01-01

    Purpose The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventative measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis and may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. Materials and Methods A comprehensive review of the English language literature was performed using PUBMED. When necessary, authoritative texts on relevant subtopics were consulted. Results The genetic composition, anatomic structure and physiologic function of Drosophila Malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration, and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis, including genetically linked and environmentally induced stones, have been developed. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. Conclusions The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease. PMID:23500641

  14. Current humanized mouse models for studying human immunology and HIV-1 immuno-pathogenesis

    Institute of Scientific and Technical Information of China (English)

    MEISSNER; Eric

    2010-01-01

    A robust animal model for "hypothesis-testing/mechanistic" research in human immunology and immuno-pathology should meet the following criteria.First,it has well-studied hemato-lymphoid organs and target cells similar to those of humans.Second,the human pathogens establish infection and lead to relevant diseases.Third,it is genetically inbred and can be manipulated via genetic,immunological and pharmacological means.Many human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life cycle.The mouse with a reconstituted human immune system and other human target organs is a good candidate.A number of human-mouse chimeric models with human immune cells have been developed in the past 20 years,but most with only limited success due to the selective engraftment of xeno-reactive human T cells in hu-PBL-SCID mice or the lack of significant human immune responses in the SCID-hu Thy/Liv mouse.This review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate models.It also reviews the recent progress in the development of humanized mouse models with a functional human immune system,especially the recent progress in the immunodeficient mice that carry a defective gammaC gene.NOD/SCID/gammaC-/(NOG or NSG) or the Rag2-/-/gammaC-/double knockout (DKO) mice,which lack NK as well as T and B cells (NTB-null mice),have been used to reconstitute a functional human immune system in central and peripheral lymphoid organs with human CD34+ HSC.These NTB-hu HSC humanized models have been used to investigate HIV-1 infection,immuno-pathogenesis and therapeutic interventions.Such models,with further improvements,will contribute to study human immunology,human-tropic pathogens as well as human stem cell biology in the tissue development and function in vivo.

  15. Mice with human immune system components as in vivo models for infections with human pathogens.

    Science.gov (United States)

    Rämer, Patrick C; Chijioke, Obinna; Meixlsperger, Sonja; Leung, Carol S; Münz, Christian

    2011-03-01

    Many pathogens relevant to human disease do not infect other animal species. Therefore, animal models that reconstitute or harbor human tissues are explored as hosts for these. In this review, we will summarize recent advances to utilize mice with human immune system components, reconstituted from hematopoietic progenitor cells in vivo. Such mice can be used to study human pathogens that replicate in leukocytes. In addition to studying the replication of these pathogens, the reconstituted human immune system components can also be analyzed for initiating immune responses and control against these infections. Moreover, these new animal models of human infectious disease should replicate the reactivity of the human immune system to vaccine candidates and, especially, the adjuvants contained in them, more faithfully.

  16. A novel mouse model for stable engraftment of a human immune system and human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Helene Strick-Marchand

    Full Text Available Hepatic infections by hepatitis B virus (HBV, hepatitis C virus (HCV and Plasmodium parasites leading to acute or chronic diseases constitute a global health challenge. The species tropism of these hepatotropic pathogens is restricted to chimpanzees and humans, thus model systems to study their pathological mechanisms are severely limited. Although these pathogens infect hepatocytes, disease pathology is intimately related to the degree and quality of the immune response. As a first step to decipher the immune response to infected hepatocytes, we developed an animal model harboring both a human immune system (HIS and human hepatocytes (HUHEP in BALB/c Rag2-/- IL-2Rγc-/- NOD.sirpa uPAtg/tg mice. The extent and kinetics of human hepatocyte engraftment were similar between HUHEP and HIS-HUHEP mice. Transplanted human hepatocytes were polarized and mature in vivo, resulting in 20-50% liver chimerism in these models. Human myeloid and lymphoid cell lineages developed at similar frequencies in HIS and HIS-HUHEP mice, and splenic and hepatic compartments were humanized with mature B cells, NK cells and naïve T cells, as well as monocytes and dendritic cells. Taken together, these results demonstrate that HIS-HUHEP mice can be stably (> 5 months and robustly engrafted with a humanized immune system and chimeric human liver. This novel HIS-HUHEP model provides a platform to investigate human immune responses against hepatotropic pathogens and to test novel drug strategies or vaccine candidates.

  17. A novel mouse model for stable engraftment of a human immune system and human hepatocytes.

    Science.gov (United States)

    Strick-Marchand, Helene; Dusséaux, Mathilde; Darche, Sylvie; Huntington, Nicholas D; Legrand, Nicolas; Masse-Ranson, Guillemette; Corcuff, Erwan; Ahodantin, James; Weijer, Kees; Spits, Hergen; Kremsdorf, Dina; Di Santo, James P

    2015-01-01

    Hepatic infections by hepatitis B virus (HBV), hepatitis C virus (HCV) and Plasmodium parasites leading to acute or chronic diseases constitute a global health challenge. The species tropism of these hepatotropic pathogens is restricted to chimpanzees and humans, thus model systems to study their pathological mechanisms are severely limited. Although these pathogens infect hepatocytes, disease pathology is intimately related to the degree and quality of the immune response. As a first step to decipher the immune response to infected hepatocytes, we developed an animal model harboring both a human immune system (HIS) and human hepatocytes (HUHEP) in BALB/c Rag2-/- IL-2Rγc-/- NOD.sirpa uPAtg/tg mice. The extent and kinetics of human hepatocyte engraftment were similar between HUHEP and HIS-HUHEP mice. Transplanted human hepatocytes were polarized and mature in vivo, resulting in 20-50% liver chimerism in these models. Human myeloid and lymphoid cell lineages developed at similar frequencies in HIS and HIS-HUHEP mice, and splenic and hepatic compartments were humanized with mature B cells, NK cells and naïve T cells, as well as monocytes and dendritic cells. Taken together, these results demonstrate that HIS-HUHEP mice can be stably (> 5 months) and robustly engrafted with a humanized immune system and chimeric human liver. This novel HIS-HUHEP model provides a platform to investigate human immune responses against hepatotropic pathogens and to test novel drug strategies or vaccine candidates.

  18. New Metacognitive Model for Human Performance Technology

    Science.gov (United States)

    Turner, John R.

    2011-01-01

    Addressing metacognitive functions has been shown to improve performance at the individual, team, group, and organizational levels. Metacognition is beginning to surface as an added cognate discipline for the field of human performance technology (HPT). Advances from research in the fields of cognition and metacognition offer a place for HPT to…

  19. New Metacognitive Model for Human Performance Technology

    Science.gov (United States)

    Turner, John R.

    2011-01-01

    Addressing metacognitive functions has been shown to improve performance at the individual, team, group, and organizational levels. Metacognition is beginning to surface as an added cognate discipline for the field of human performance technology (HPT). Advances from research in the fields of cognition and metacognition offer a place for HPT to…

  20. [Prevention of fungal infections in hospitalized patients].

    Science.gov (United States)

    Seeliger, H P; Schröter, G

    1984-06-01

    Hospital acquired infections due to fungi are primarily caused by yeast species of the genus Candida and mould species of the genus Aspergillus. Underlying disease with severely impaired defence mechanisms as well as certain forms of immunosuppressive and aggressive chemotherapy are the most important prerequisites for such secondary fungal infections. Aspergillus spec. usually infect man via exogenous routes, whereas Candida spec. mostly originate from the patient's own microbial flora. Under certain circumstances invasion of tissues follows (endomycosis). Exogenous Candida infections may likewise occur through contaminated hands of personnel and medical devices. The density of yeast cell distribution in hospital wards decreases with the distance from the primary source: the Candida infected human patient. Preventive measures protecting the patient at risk include: Permanent surveillance by routine cultural and serological examinations for the detection of an early infection of the skin, mouth, oesophagus, urinary tract, vagina and the bowel. Monitoring of patients is essential for early detection of dissemination and contributes to the control of fungal decontamination measures. Selective local decontamination is effected by the use of nonabsorbable compounds such as nystatin and amphotericin B in the gastrointestinal tract, and in oral and genital mucous membranes. Oral administration of ketoconazole has also been recommended. For the disinfection of skin appropriate chemicals are available. In the control of the environment of the endangered patient special attention must be paid to meticulous management of catheters. These measures are to be supported by careful disinfection policy concerning the hands of personnel and medical equipment.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Standard methods for fungal brood disease research.

    Science.gov (United States)

    Jensen, Annette Bruun; Aronstein, Kathrine; Flores, José Manuel; Vojvodic, Svjetlana; Palacio, María Alejandra; Spivak, Marla

    2013-01-01

    Chalkbrood and stonebrood are two fungal diseases associated with honey bee brood. Chalkbrood, caused by Ascosphaera apis, is a common and widespread disease that can result in severe reduction of emerging worker bees and thus overall colony productivity. Stonebrood is caused by Aspergillus spp. that are rarely observed, so the impact on colony health is not very well understood. A major concern with the presence of Aspergillus in honey bees is the production of airborne conidia, which can lead to allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, or even invasive aspergillosis in lung tissues upon inhalation by humans. In the current chapter we describe the honey bee disease symptoms of these fungal pathogens. In addition, we provide research methodologies and protocols for isolating and culturing, in vivo and in vitro assays that are commonly used to study these host pathogen interactions. We give guidelines on the preferred methods used in current research and the application of molecular techniques. We have added photographs, drawings and illustrations to assist bee-extension personnel and bee scientists in the control of these two diseases.

  2. Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

    Science.gov (United States)

    Lee, Robert J.; Workman, Alan D.; Carey, Ryan M.; Chen, Bei; Rosen, Phillip L.; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.

    2016-01-01

    Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6–12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases. PMID:27623953

  3. Subseafloor basalts as fungal habitats

    Science.gov (United States)

    Ivarsson, M.

    2012-09-01

    The oceanic crust is believed to host the largest potential habitat for microbial life on Earth, yet, still we lack substantial information about the abundance, diversity, and consequence of its biosphere. The last two decades have involved major research accomplishments within this field and a change in view of the ocean crust and its potential to harbour life. Here fossilised fungal colonies in subseafloor basalts are reported from three different seamounts in the Pacific Ocean. The fungal colonies consist of various characteristic structures interpreted as fungal hyphae, fruit bodies and spores. The fungal hyphae are well preserved with morphological characteristics such as hyphal walls, septa, thallic conidiogenesis, and hyphal tips with hyphal vesicles within. The fruit bodies consist of large (∼50-200 µm in diameter) body-like structures with a defined outer membrane and an interior filled with calcite. The fruit bodies have at some stage been emptied of their contents of spores and filled by carbonate-forming fluids. A few fruit bodies not filled by calcite and with spores still within support this interpretation. Spore-like structures (ranging from a few µm to ∼20 µm in diameter) are also observed outside of the fruit bodies and in some cases concentrated to openings in the membrane of the fruit bodies. The hyphae, fruit bodies and spores are all closely associated with a crust lining the vein walls that probably represent a mineralized biofilm. The results support a fungal presence in deep subseafloor basalts and indicate that such habitats were vital between ∼81 and 48 Ma.

  4. Human performance modeling for system of systems analytics.

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kevin R.; Lawton, Craig R.; Basilico, Justin Derrick; Longsine, Dennis E. (INTERA, Inc., Austin, TX); Forsythe, James Chris; Gauthier, John Henry; Le, Hai D.

    2008-10-01

    A Laboratory-Directed Research and Development project was initiated in 2005 to investigate Human Performance Modeling in a System of Systems analytic environment. SAND2006-6569 and SAND2006-7911 document interim results from this effort; this report documents the final results. The problem is difficult because of the number of humans involved in a System of Systems environment and the generally poorly defined nature of the tasks that each human must perform. A two-pronged strategy was followed: one prong was to develop human models using a probability-based method similar to that first developed for relatively well-understood probability based performance modeling; another prong was to investigate more state-of-art human cognition models. The probability-based modeling resulted in a comprehensive addition of human-modeling capability to the existing SoSAT computer program. The cognitive modeling resulted in an increased understanding of what is necessary to incorporate cognition-based models to a System of Systems analytic environment.

  5. Understanding What We Do: Emerging Models for Human Rights Education

    Science.gov (United States)

    Tibbitts, Felisa

    2002-07-01

    The author presents three approaches to contemporary human rights education practice: the Values and Awareness Model, the Accountability Model and the Transformational Model. Each model is associated with particular target groups, contents and strategies. The author suggests that these models can lend themselves to theory development and research in what might be considered an emerging educational field. Human rights education can be further strengthened through the appropriate use oflearning theory, as well as through the setting of standards for trainer preparation and program content, and through evaluating the impact of programs in terms of reaching learner goals (knowledge, values and skills) and contributing to social change.

  6. Biostereometric Data Processing In ERGODATA: Choice Of Human Body Models

    Science.gov (United States)

    Pineau, J. C.; Mollard, R.; Sauvignon, M.; Amphoux, M.

    1983-07-01

    The definition of human body models was elaborated with anthropometric data from ERGODATA. The first model reduces the human body into a series of points and lines. The second model is well adapted to represent volumes of each segmentary element. The third is an original model built from the conventional anatomical points. Each segment is defined in space by a tri-angular plane located with its 3-D coordinates. This new model can answer all the processing possibilities in the field of computer-aided design (C.A.D.) in ergonomy but also biomechanics and orthopaedics.

  7. Human Digital Modeling & Hand Scanning Lab

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory incorporates specialized scanning equipment, computer workstations and software applications for the acquisition and analysis of digitized models of...

  8. Medical mycology and fungal immunology: new research perspectives addressing a major world health challenge.

    Science.gov (United States)

    Gow, Neil A R; Netea, Mihai G

    2016-12-05

    Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV. To address these global threats to human health, more research is urgently needed to understand the immunopathology of fungal disease and human disease susceptibility in order to augment the advances being made in fungal diagnostics and drug development. Here, we highlight some recent advances in basic research in medical mycology and fungal immunology that are beginning to inform clinical decisions and options for personalized medicine, vaccine development and adjunct immunotherapies.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Authors.

  9. Medical mycology and fungal immunology: new research perspectives addressing a major world health challenge

    Science.gov (United States)

    Gow, Neil A. R.; Netea, Mihai G.

    2016-01-01

    Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV. To address these global threats to human health, more research is urgently needed to understand the immunopathology of fungal disease and human disease susceptibility in order to augment the advances being made in fungal diagnostics and drug development. Here, we highlight some recent advances in basic research in medical mycology and fungal immunology that are beginning to inform clinical decisions and options for personalized medicine, vaccine development and adjunct immunotherapies. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080988

  10. Synthetic vision and emotion calculation in intelligent virtual human modeling.

    Science.gov (United States)

    Zhao, Y; Kang, J; Wright, D K

    2007-01-01

    The virtual human technique can already provide vivid and believable human behaviour in more and more scenarios. Virtual humans are expected to replace real humans in hazardous situations to undertake tests and feed back valuable information. This paper will introduce a virtual human with a novel collision-based synthetic vision, short-term memory model and a capability to implement emotion calculation and decision making. The virtual character based on this model can 'see' what is in its field of view (FOV) and remember those objects. After that, a group of affective computing equations have been introduced. These equations have been implemented into a proposed emotion calculation process to enlighten emotion for virtual intelligent humans.

  11. Modelling mutational landscapes of human cancers in vitro

    Science.gov (United States)

    Olivier, Magali; Weninger, Annette; Ardin, Maude; Huskova, Hana; Castells, Xavier; Vallée, Maxime P.; McKay, James; Nedelko, Tatiana; Muehlbauer, Karl-Rudolf; Marusawa, Hiroyuki; Alexander, John; Hazelwood, Lee; Byrnes, Graham; Hollstein, Monica; Zavadil, Jiri

    2014-03-01

    Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data.

  12. Fungal lysis by a soil bacterium fermenting cellulose.

    Science.gov (United States)

    Tolonen, Andrew C; Cerisy, Tristan; El-Sayyed, Hafez; Boutard, Magali; Salanoubat, Marcel; Church, George M

    2015-08-01

    Recycling of plant biomass by a community of bacteria and fungi is fundamental to carbon flow in terrestrial ecosystems. Here we report how the plant fermenting, soil bacterium Clostridium phytofermentans enhances growth on cellulose by simultaneously lysing and consuming model fungi from soil. We investigate the mechanism of fungal lysis to show that among the dozens of different glycoside hydrolases C. phytofermentans secretes on cellulose, the most highly expressed enzymes degrade fungi rather than plant substrates. These enzymes, the GH18 Cphy1799 and Cphy1800, synergize to hydrolyse chitin, a main component of the fungal cell wall. Purified enzymes inhibit fungal growth and mutants lacking either GH18 grow normally on cellulose and other plant substrates, but have a reduced ability to hydrolyse chitinous substrates and fungal hyphae. Thus, C. phytofermentans boosts growth on cellulose by lysing fungi with its most highly expressed hydrolases, highlighting the importance of fungal interactions to the ecology of cellulolytic bacteria. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Cyberpsychology: a human-interaction perspective based on cognitive modeling.

    Science.gov (United States)

    Emond, Bruno; West, Robert L

    2003-10-01

    This paper argues for the relevance of cognitive modeling and cognitive architectures to cyberpsychology. From a human-computer interaction point of view, cognitive modeling can have benefits both for theory and model building, and for the design and evaluation of sociotechnical systems usability. Cognitive modeling research applied to human-computer interaction has two complimentary objectives: (1) to develop theories and computational models of human interactive behavior with information and collaborative technologies, and (2) to use the computational models as building blocks for the design, implementation, and evaluation of interactive technologies. From the perspective of building theories and models, cognitive modeling offers the possibility to anchor cyberpsychology theories and models into cognitive architectures. From the perspective of the design and evaluation of socio-technical systems, cognitive models can provide the basis for simulated users, which can play an important role in usability testing. As an example of application of cognitive modeling to technology design, the paper presents a simulation of interactive behavior with five different adaptive menu algorithms: random, fixed, stacked, frequency based, and activation based. Results of the simulation indicate that fixed menu positions seem to offer the best support for classification like tasks such as filing e-mails. This research is part of the Human-Computer Interaction, and the Broadband Visual Communication research programs at the National Research Council of Canada, in collaboration with the Carleton Cognitive Modeling Lab at Carleton University.

  14. Modeling Human Behaviour with Higher Order Logic: Insider Threats

    NARCIS (Netherlands)

    Boender, Jaap; Ivanova, Marieta Georgieva; Kammüller, Florian; Primierio, Giuseppe

    2014-01-01

    In this paper, we approach the problem of modeling the human component in technical systems with a view on the difference between the use of model and theory in sociology and computer science. One aim of this essay is to show that building of theories and models for sociology can be compared and imp

  15. Formal modelling techniques in human-computer interaction

    NARCIS (Netherlands)

    Haan, de G.; Veer, van der G.C.; Vliet, van J.C.

    1991-01-01

    This paper is a theoretical contribution, elaborating the concept of models as used in Cognitive Ergonomics. A number of formal modelling techniques in human-computer interaction will be reviewed and discussed. The analysis focusses on different related concepts of formal modelling techniques in hum

  16. Ice nucleation and its effect on the atmospheric transport of fungal spores from the classes Agaricomycetes, Ustilaginomycetes, and Eurotiomycetes

    Science.gov (United States)

    Haga, D. I.; Burrows, S. M.; Iannone, R.; Wheeler, M. J.; Mason, R.; Chen, J.; Polishchuk, E. A.; Pöschl, U.; Bertram, A. K.

    2014-02-01

    Ice nucleation on fungal spores may affect the frequency and properties of ice and mixed-phase clouds. We studied the ice nucleation properties of 12 different species of fungal spores chosen from three classes: Agaricomycetes, Ustilaginomycetes, and Eurotiomycetes. Agaricomycetes include many types of mushroom species and are cosmopolitan. Ustilaginomycetes are agricultural pathogens and have caused widespread damage to crops. Eurotiomycetes are found on all types of decaying material and include important human allergens. We focused on these classes since they are thought to be abundant in the atmosphere and because there is very little information on the ice nucleation ability of these classes of spores in the literature. All of the fungal spores investigated were found to cause freezing of water droplets at temperatures warmer than homogeneous freezing. The cumulative number of ice nuclei per spore was 0.001 at temperatures between -19 °C and -29 °C, 0.01 between -25.5 °C and -31 °C, and 0.1 between -26 °C and -36 °C. On average, the order of ice nucleating ability for these spores is Ustilaginomycetes > Agaricomycetes ≃ Eurotiomycetes. We show that at temperatures below -20 °C, all of the fungal spores studied here are less efficient ice nuclei compared to Asian mineral dust on a per surface area basis. We used our new freezing results together with data in the literature to compare the freezing temperatures of spores from the phyla Basidiomycota and Ascomycota, which together make up 98% of known fungal species found on Earth. The data show that within both phyla (Ascomycota and Basidiomycota) there is a wide range of freezing properties, and also that the variation within a phylum is greater than the variation between the average freezing properties of the phyla. Using a global chemistry-climate transport model, we investigated whether ice nucleation on the studied spores, followed by precipitation, can influence the atmospheric transport and

  17. Human Spaceflight Architecture Model (HSFAM) Data Dictionary

    Science.gov (United States)

    Shishko, Robert

    2016-01-01

    HSFAM is a data model based on the DoDAF 2.02 data model with some for purpose extensions. These extensions are designed to permit quantitative analyses regarding stakeholder concerns about technical feasibility, configuration and interface issues, and budgetary and/or economic viability.

  18. Behavior genetic modeling of human fertility

    DEFF Research Database (Denmark)

    Rodgers, J L; Kohler, H P; Kyvik, K O;

    2001-01-01

    Try) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males...

  19. Molecular Identification of Human Fungal Pathogens

    Science.gov (United States)

    2014-05-01

    military environment are urgently needed. The objective of this proposal is to develop a rapid molecular diagnostic assay using a new PCR technology...called LATE- PCR (Linear-After-The-Exponential Polymerase Chain Reaction). This study has three aims: 1) selection of targets suitable for a multiplex PCR ...reaction, 2) design of primers and probes for each class of fungus, all of which will be compatible in a single reaction, and 3) pilot testing on

  20. The Chemical Basis of Fungal Bioluminescence.

    Science.gov (United States)

    Purtov, Konstantin V; Petushkov, Valentin N; Baranov, Mikhail S; Mineev, Konstantin S; Rodionova, Natalja S; Kaskova, Zinaida M; Tsarkova, Aleksandra S; Petunin, Alexei I; Bondar, Vladimir S; Rodicheva, Emma K; Medvedeva, Svetlana E; Oba, Yuichi; Oba, Yumiko; Arseniev, Alexander S; Lukyanov, Sergey; Gitelson, Josef I; Yampolsky, Ilia V

    2015-07-06

    Many species of fungi naturally produce light, a phenomenon known as bioluminescence, however, the fungal substrates used in the chemical reactions that produce light have not been reported. We identified the fungal compound luciferin 3-hydroxyhispidin, which is biosynthesized by oxidation of the precursor hispidin, a known fungal and plant secondary metabolite. The fungal luciferin does not share structural similarity with the other eight known luciferins. Furthermore, it was shown that 3-hydroxyhispidin leads to bioluminescence in extracts from four diverse genera of luminous fungi, thus suggesting a common biochemical mechanism for fungal bioluminescence.

  1. Phase transitions in models of human cooperation

    Science.gov (United States)

    Perc, Matjaž

    2016-08-01

    If only the fittest survive, why should one cooperate? Why should one sacrifice personal benefits for the common good? Recent research indicates that a comprehensive answer to such questions requires that we look beyond the individual and focus on the collective behavior that emerges as a result of the interactions among individuals, groups, and societies. Although undoubtedly driven also by culture and cognition, human cooperation is just as well an emergent, collective phenomenon in a complex system. Nonequilibrium statistical physics, in particular the collective behavior of interacting particles near phase transitions, has already been recognized as very valuable for understanding counterintuitive evolutionary outcomes. However, unlike pairwise interactions among particles that typically govern solid-state physics systems, interactions among humans often involve group interactions, and they also involve a larger number of possible states even for the most simplified description of reality. Here we briefly review research done in the realm of the public goods game, and we outline future research directions with an emphasis on merging the most recent advances in the social sciences with methods of nonequilibrium statistical physics. By having a firm theoretical grip on human cooperation, we can hope to engineer better social systems and develop more efficient policies for a sustainable and better future.

  2. Human Engineering Modeling and Performance Lab Study Project

    Science.gov (United States)

    Oliva-Buisson, Yvette J.

    2014-01-01

    The HEMAP (Human Engineering Modeling and Performance) Lab is a joint effort between the Industrial and Human Engineering group and the KAVE (Kennedy Advanced Visualiations Environment) group. The lab consists of sixteen camera system that is used to capture human motions and operational tasks, through te use of a Velcro suit equipped with sensors, and then simulate these tasks in an ergonomic software package know as Jac, The Jack software is able to identify the potential risk hazards.

  3. Fungal treated lignocellulosic biomass as ruminant feed ingredient: a review.

    Science.gov (United States)

    van Kuijk, S J A; Sonnenberg, A S M; Baars, J J P; Hendriks, W H; Cone, J W

    2015-01-01

    In ruminant nutrition, there is an increasing interest for ingredients that do not compete with human nutrition. Ruminants are specialists in digesting carbohydrates in plant cell walls; therefore lignocellulosic biomass has potential in ruminant nutrition. The presence of lignin in biomass, however, limits the effective utilization of cellulose and hemicellulose. Currently, most often chemical and/or physical treatments are used to degrade lignin. White rot fungi are selective lignin degraders and can be a potential alternative to current methods which involve potentially toxic chemicals and expensive equipment. This review provides an overview of research conducted to date on fungal pretreatment of lignocellulosic biomass for ruminant feeds. White rot fungi colonize lignocellulosic biomass, and during colonization produce enzymes, radicals and other small compounds to breakdown lignin. The mechanisms on how these fungi degrade lignin are not fully understood, but fungal strain, the origin of lignocellulose and culture conditions have a major effect on the process. Ceriporiopsis subvermispora and Pleurotus eryngii are the most effective fungi to improve the nutritional value of biomass for ruminant nutrition. However, conclusions on the effectiveness of fungal delignification are difficult to draw due to a lack of standardized culture conditions and information on fungal strains used. Methods of analysis between studies are not uniform for both chemical analysis and in vitro degradation measurements. In vivo studies are limited in number and mostly describing digestibility after mushroom production, when the fungus has degraded cellulose to derive energy for fruit body development. Optimization of fungal pretreatment is required to shorten the process of delignification and make it more selective for lignin. In this respect, future research should focus on optimization of culture conditions and gene expression to obtain a better understanding of the mechanisms

  4. Human vascular model with defined stimulation medium - a characterization study.

    Science.gov (United States)

    Huttala, Outi; Vuorenpää, Hanna; Toimela, Tarja; Uotila, Jukka; Kuokkanen, Hannu; Ylikomi, Timo; Sarkanen, Jertta-Riina; Heinonen, Tuula

    2015-01-01

    The formation of blood vessels is a vital process in embryonic development and in normal physiology. Current vascular modelling is mainly based on animal biology leading to species-to-species variation when extrapolating the results to humans. Although there are a few human cell based vascular models available these assays are insufficiently characterized in terms of culture conditions and developmental stage of vascular structures. Therefore, well characterized vascular models with human relevance are needed for basic research, embryotoxicity testing, development of therapeutic strategies and for tissue engineering. We have previously shown that the in vitro vascular model based on co-culture of human adipose stromal cells (hASC) and human umbilical vein endothelial cells (HUVEC) is able to induce an extensive vascular-like network with high reproducibility. In this work we developed a defined serum-free vascular stimulation medium (VSM) and performed further characterization in terms of cell identity, maturation and structure to obtain a thoroughly characterized in vitro vascular model to replace or reduce corresponding animal experiments. The results showed that the novel vascular stimulation medium induced intact and evenly distributed vascular-like network with morphology of mature vessels. Electron microscopic analysis assured the three-dimensional microstructure of the network containing lumen. Additionally, elevated expressions of the main human angiogenesis-related genes were detected. In conclusion, with the new defined medium the vascular model can be utilized as a characterized test system for chemical testing as well as in creating vascularized tissue models.

  5. Climate change and predicted trend of fungal keratitis in Egypt.

    Science.gov (United States)

    Saad-Hussein, A; El-Mofty, H M; Hassanien, M A

    2011-06-01

    Rising rates of invasive fungal infections may be linked to global climate change. A study was made of the trend of ophthalmic fungal corneal keratitis in the greater Cairo area of Egypt and its association with climate records during the same period. Data on diagnosed cases of fungal keratitis were collected from records of ophthalmic departments of Cairo University hospital and atmospheric temperature and humidity for the greater Cairo area were obtained from online records. Statistical analysis showed a significant increase in the relative frequency of keratomycosis during 1997-2007. The rise correlated significantly with rises n min,mum temperature and the maximum atmospheric humidity in the greater Cairo area over the same period (after exclusion of the effect of the maximum atmos pheric temperature). The predicted increase in keratomycosis up to the year 2030 corresponds to predicted increases in CO2 emissions and surface temperature from climate change models for Egypt.

  6. Heterologous production of fungal secondary metabolites in Aspergilli

    DEFF Research Database (Denmark)

    Anyaogu, Diana Chinyere; Mortensen, Uffe Hasbro

    2015-01-01

    Fungal natural products comprise a wide range of compounds. Some are medically attractive as drugs and drug leads, some are used as food additives, while others are harmful mycotoxins. In recent years the genome sequence of several fungi has become available providing genetic information of a large...... number of putative biosynthetic pathways. However, compound discovery is difficult as the genes required for the production of the compounds often are silent or barely expressed under laboratory conditions. Furthermore, the lack of available tools for genetic manipulation of most fungal species hinders...... pathway discovery. Heterologous expression of the biosynthetic pathway in model systems or cell factories facilitates product discovery, elucidation, and production. This review summarizes the recent strategies for heterologous expression of fungal biosynthetic pathways in Aspergilli....

  7. Agency, Values, and Well-Being: A Human Development Model

    Science.gov (United States)

    Welzel, Christian; Inglehart, Ronald

    2010-01-01

    This paper argues that feelings of agency are linked to human well-being through a sequence of adaptive mechanisms that promote human development, once existential conditions become permissive. In the first part, we elaborate on the evolutionary logic of this model and outline why an evolutionary perspective is helpful to understand changes in…

  8. Modelling human actions on lightweight structures: experimental and numerical developments

    Directory of Open Access Journals (Sweden)

    Živanović S.

    2015-01-01

    Full Text Available This paper presents recent, numerical and experimental, developments in modelling dynamic loading generated by humans. As modern structures with exposure to human-induced loading, such as footbridges, building floors and grandstands, are becoming ever lighter and more slender, they are increasingly susceptible to vibration under human-induced dynamic excitation, such as walking, jumping, running and bobbing, and their vibration serviceability assessment is often a deciding factor in the design process. While simplified modelling of the human using a harmonic force was sufficient for assessment of vibration performance of more robust structures a few decades ago, the higher fidelity models are required in the contemporary design. These models are expected not only to describe both temporal and spectral features of the force signal more accurately, but also to capture the influence, psychological and physiological, of human-structure and human-human interaction mechanisms on the human kinematics, and consequently on the force generated and the resulting vibration response. Significant advances have been made in both the research studies and design guidance. This paper reports the key developments and identifies the scope for further research.

  9. How do humans inspect BPMN models: an exploratory study

    DEFF Research Database (Denmark)

    Haisjackl, Cornelia; Soffer, Pnina; Lim, Shao Yi

    2016-01-01

    by humans, what strategies are taken, what challenges arise, and what cognitive processes are involved. This paper contributes toward such an understanding and reports an exploratory study investigating how humans identify and classify quality issues in BPMN process models. Providing preliminary answers...

  10. Relevance of animal models to human tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Blanchet Pierre J

    2012-03-01

    Full Text Available Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.

  11. DEVELOPMENT OF 2D HUMAN BODY MODELING USING THINNING ALGORITHM

    Directory of Open Access Journals (Sweden)

    K. Srinivasan

    2010-11-01

    Full Text Available Monitoring the behavior and activities of people in Video surveillance has gained more applications in Computer vision. This paper proposes a new approach to model the human body in 2D view for the activity analysis using Thinning algorithm. The first step of this work is Background subtraction which is achieved by the frame differencing algorithm. Thinning algorithm has been used to find the skeleton of the human body. After thinning, the thirteen feature points like terminating points, intersecting points, shoulder, elbow, and knee points have been extracted. Here, this research work attempts to represent the body model in three different ways such as Stick figure model, Patch model and Rectangle body model. The activities of humans have been analyzed with the help of 2D model for the pre-defined poses from the monocular video data. Finally, the time consumption and efficiency of our proposed algorithm have been evaluated.

  12. Fungal rhinosinusitis: what every allergist should know.

    Science.gov (United States)

    Callejas, C A; Douglas, R G

    2013-08-01

    The interaction between fungi and the sinonasal tract results in a diverse range of diseases with an equally broad spectrum of clinical severity. The classification of these interactions has become complex, and this review seeks to rationalize and simplify the approach to fungal diseases of the nose and paranasal sinuses. These conditions may be discussed under two major headings: non-invasive disease (localized fungal colonization, fungal ball and allergic fungal rhinosinusitis) and invasive disease (acute invasive rhinosinusitis, chronic invasive rhinosinusitis and granulomatous invasive rhinosinusitis). A diagnosis of fungal rhinosinusitis is established by combining findings on history, clinical examination, laboratory testing, imaging and histopathology. The immunocompetence of the patient is of great importance, as invasive fungal rhinosinusitis is uncommon in immunocompetent patients. With the exception of localized fungal colonization, treatment of all forms of fungal rhinosinusitis relies heavily on surgery. Systemic antifungal agents are a fundamental component in the treatment of invasive forms, but are not indicated for the treatment of the non-invasive forms. Antifungal drugs may have a role as adjuvant therapy in allergic fungal rhinosinusitis, but evidence is poor to support recommendations. Randomized controlled trials need to be performed to confirm the benefit of immunotherapy in the treatment of allergic fungal rhinosinusitis. In this article, we will summarize the current literature, addressing the controversies regarding the diagnosis and management of fungal rhinosinusitis, and focussing on those aspects which are important for clinical immunologists and allergists.

  13. Box model for channels of human migration

    CERN Document Server

    Vitanov, Nikolay K

    2016-01-01

    We discuss a mathematical model of migration channel based on the truncated Waring distribution. The truncated Waring distribution is obtained for a more general model of motion of substance through a channel containing finite number of boxes. The model is applied then for case of migrants moving through a channel consisting of finite number of countries or cities. The number of migrants in the channel strongly depends on the number of migrants that enter the channel through the country of entrance. It is shown that if the final destination country is very popular then large percentage of migrants may concentrate there.

  14. A Model of Genetic Variation in Human Social Networks

    CERN Document Server

    Fowler, James H; Christakis, Nicholas A

    2008-01-01

    Social networks influence the evolution of cooperation and they exhibit strikingly systematic patterns across a wide range of human contexts. Both of these facts suggest that variation in the topological attributes of human social networks might have a genetic basis. While genetic variation accounts for a significant portion of the variation in many complex social behaviors, the heritability of egocentric social network attributes is unknown. Here we show that three of these attributes (in-degree, transitivity, and centrality) are heritable. We then develop a "mirror network" method to test extant network models and show that none accounts for observed genetic variation in human social networks. We propose an alternative "attract and introduce" model that generates significant heritability as well as other important network features, and we show that this model with two simple forms of heterogeneity is well suited to the modeling of real social networks in humans. These results suggest that natural selection ...

  15. Pharmacological migraine provocation: a human model of migraine

    DEFF Research Database (Denmark)

    Ashina, Messoud; Hansen, Jakob Møller

    2010-01-01

    In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of possible new antimigraine agents. Animal models enable the study of vascular responses, neurogenic inflammation, and peptide release, and thus have provided leads in the search...... for migraine mechanisms. So far, however, animal models cannot predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model....... If a naturally occurring substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed...

  16. Dynamic Human Body Modeling Using a Single RGB Camera

    Directory of Open Access Journals (Sweden)

    Haiyu Zhu

    2016-03-01

    Full Text Available In this paper, we present a novel automatic pipeline to build personalized parametric models of dynamic people using a single RGB camera. Compared to previous approaches that use monocular RGB images, our system can model a 3D human body automatically and incrementally, taking advantage of human motion. Based on coarse 2D and 3D poses estimated from image sequences, we first perform a kinematic classification of human body parts to refine the poses and obtain reconstructed body parts. Next, a personalized parametric human model is generated by driving a general template to fit the body parts and calculating the non-rigid deformation. Experimental results show that our shape estimation method achieves comparable accuracy with reconstructed models using depth cameras, yet requires neither user interaction nor any dedicated devices, leading to the feasibility of using this method on widely available smart phones.

  17. Dynamic Human Body Modeling Using a Single RGB Camera.

    Science.gov (United States)

    Zhu, Haiyu; Yu, Yao; Zhou, Yu; Du, Sidan

    2016-03-18

    In this paper, we present a novel automatic pipeline to build personalized parametric models of dynamic people using a single RGB camera. Compared to previous approaches that use monocular RGB images, our system can model a 3D human body automatically and incrementally, taking advantage of human motion. Based on coarse 2D and 3D poses estimated from image sequences, we first perform a kinematic classification of human body parts to refine the poses and obtain reconstructed body parts. Next, a personalized parametric human model is generated by driving a general template to fit the body parts and calculating the non-rigid deformation. Experimental results show that our shape estimation method achieves comparable accuracy with reconstructed models using depth cameras, yet requires neither user interaction nor any dedicated devices, leading to the feasibility of using this method on widely available smart phones.

  18. Human Communication--A New Model.

    Science.gov (United States)

    McLeish, John

    1978-01-01

    Pavlov's organism-in-the-environment model was adapted to a functional analysis of communication, expecially abstract and symbolic activities. A classification of discrimination response and reinforcement patterns was given. (CP)

  19. Modeling and Mapping of Human Source Data

    Science.gov (United States)

    2011-03-08

    developing a functional framework (and identifying relevant models and algorithms) is to follow the Joint Directors of Laboratories ( JDL ) data fusion...process model ([32], [18]) and explore an analog between traditional fusion processing (at the JDL level 0 and level 1 sub-processes) for physical sensors...this work is shown below. A diagrammatic summary of the analysis is shown in Figures 5 and 6. Figure 4: Information Fusion Hierarchy ( JDL Levels

  20. Human Operator Modeling for Aerial Tracking.

    Science.gov (United States)

    1980-12-01

    SECuRIT CLASSIFICATION OF THIS PAGE(Wh~.n Dwte Enteved) PREFACE This research project was funded by he Air Force Aerospace Medical Research Laboratory...mrad). We assume that the threshold changes gradually around t = 305 sec, where GT decreases from 7 to 4G . These assumption were applied, regardless of...is the subject attained G; (Equation (2.43)) and (; = 4g = minimalA Az mai G;z level, below which human performance is assumed not to be affected

  1. Testing modern human out-of-Africa dispersal models and implications for modern human origins.

    Science.gov (United States)

    Reyes-Centeno, Hugo; Hubbe, Mark; Hanihara, Tsunehiko; Stringer, Chris; Harvati, Katerina

    2015-10-01

    The modern human expansion process out of Africa has important implications for understanding the genetic and phenotypic structure of extant populations. While intensely debated, the primary hypotheses focus on either a single dispersal or multiple dispersals out of the continent. Here, we use the human fossil record from Africa and the Levant, as well as an exceptionally large dataset of Holocene human crania sampled from Asia, to model ancestor-descendant relationships along hypothetical dispersal routes. We test the spatial and temporal predictions of competing out-of-Africa models by assessing the correlation of geographical distances between populations and measures of population differentiation derived from quantitative cranial phenotype data. Our results support a model in which extant Australo-Melanesians are descendants of an initial dispersal out of Africa by early anatomically modern humans, while all other populations are descendants of a later migration wave. Our results have implications for understanding the complexity of modern human origins and diversity.

  2. Inverse Kinematic Analysis of Human Hand Thumb Model

    Science.gov (United States)

    Toth-Tascau, Mirela; Pater, Flavius; Stoia, Dan Ioan; Menyhardt, Karoly; Rosu, Serban; Rusu, Lucian; Vigaru, Cosmina

    2011-09-01

    This paper deals with a kinematic model of the thumb of the human hand. The proposed model has 3 degrees of freedom being able to model the movements of the thumb tip with respect to the wrist joint centre. The kinematic equations are derived based on Denavit-Hartenberg Convention and solved in both direct and inverse way. Inverse kinematic analysis of human hand thumb model reveals multiple and connected solutions which are characteristic to nonlinear systems when the number of equations is greater than number of unknowns and correspond to natural movements of the finger.

  3. Recent progress in vaccines against fungal diseases.

    Science.gov (United States)

    Cassone, Antonio; Casadevall, Arturo

    2012-08-01

    Diseases caused by fungi are increasingly impacting the health of the human population and now account for a large fraction of infectious disease complications in individuals with impaired immunity or breached tissue defenses. Antifungal therapy is often of limited effectiveness in these patients, resulting into treatment failures, chronic infections and unacceptable rates of mortality, morbidity and their associated costs. Consequently there is a real medical need for new treatments and preventive measures to combat fungal diseases and, toward this goal, safe and efficacious vaccines would constitute major progress. After decades of complacency and neglect of this critically important field of research, remarkable progress has been made in recent years. A number of highly immunogenic and protective vaccine formulations in preclinical setting have been developed, and at least two have undergone Phase 1 clinical trials as preventive and/or therapeutic tools against candidiasis.

  4. Human casualties in earthquakes: modelling and mitigation

    Science.gov (United States)

    Spence, R.J.S.; So, E.K.M.

    2011-01-01

    Earthquake risk modelling is needed for the planning of post-event emergency operations, for the development of insurance schemes, for the planning of mitigation measures in the existing building stock, and for the development of appropriate building regulations; in all of these applications estimates of casualty numbers are essential. But there are many questions about casualty estimation which are still poorly understood. These questions relate to the causes and nature of the injuries and deaths, and the extent to which they can be quantified. This paper looks at the evidence on these questions from recent studies. It then reviews casualty estimation models available, and finally compares the performance of some casualty models in making rapid post-event casualty estimates in recent earthquakes.

  5. Fungal keratitis in Lattice dystrophy

    Directory of Open Access Journals (Sweden)

    Chatterjee Samrat

    2010-01-01

    Full Text Available We report a case of fungal keratitis occurring in a patient with lattice dystrophy. A 57-year-old farmer presented with a corneal ulcer following probable entry of paddy husk in the right eye, of one month duration. Corneal scraping revealed pigmented fungal filaments while culture grew Alternaria alternata. Treatment with 5% natamycin eye drops and 1% atropine healed the infection in four weeks. We would like to draw attention to the fact that the cornea in lattice dystrophy is prone to frequent erosions and is a compromised epithelial barrier to invasion by microorganisms. Patients must be made aware of this fact and should seek attention at the earliest following any trivial trauma. Management of minor corneal abrasions in them should be directed at healing the epithelium with adequate lubricants and preventing infection with topical antibiotic prophylaxis.

  6. Structural aspects of fungal allergens.

    Science.gov (United States)

    Crameri, Reto

    2015-03-01

    Despite the increasing number of solved crystal structures of allergens, the key question why some proteins are allergenic and the vast majority is not remains unanswered. The situation is not different for fungal allergens which cover a wide variety of proteins with different chemical properties and biological functions. They cover enzymes, cell wall, secreted, and intracellular proteins which, except cross-reactive allergens, does not show any evidence for structural similarities at least at the three-dimensional level. However, from a diagnostic point of view, pure allergens biotechnologically produced by recombinant technology can provide us, in contrast to fungal extracts which are hardly producible as standardized reagents, with highly pure perfectly standardized diagnostic reagents.

  7. Nattrassia mangiferae causing fungal keratitis

    Directory of Open Access Journals (Sweden)

    Kindo A

    2010-01-01

    Full Text Available We report a case of fungal keratitis caused by the coelomycetous fungus Nattrassia mangiferae in a 70 year old gentleman, agriculturist by occupation, with a history of injury to his right eye. The scraping showed narrow septate fungal hyphae on a KOH mount, isolation of a fast growing black mould, which demonstrated hyphae and arthroconidia of varying widths typical of the Scytalidium synanamorph (S. dimidiatum. The formation of the pycnidia, which at maturity, expressed conidia. The patient was started on topical itraconazole one hourly and topical atropine thrice a day. The patient was lost to follow up hence we are not able to comment on the final outcome of the patient.

  8. Principle Generalized Net Model of a Human Stress Reaction

    Directory of Open Access Journals (Sweden)

    Anthony Shannon

    2008-04-01

    Full Text Available The present study was aimed at investigating the mechanism of a human stress reaction by means of Generalized Nets (GNs. A principle GN-model of the main structures, organs and systems of the human body taking part in the acute and chronic reaction of the organism to a stress stimulus is generated. A possible application of the GN-model of the human stress reaction for testing the effect of known or newly synthesized pharmacological products as well as of food supplements is discussed.

  9. Dynamic inverse models in human-cyber-physical systems

    Science.gov (United States)

    Robinson, Ryan M.; Scobee, Dexter R. R.; Burden, Samuel A.; Sastry, S. Shankar

    2016-05-01

    Human interaction with the physical world is increasingly mediated by automation. This interaction is characterized by dynamic coupling between robotic (i.e. cyber) and neuromechanical (i.e. human) decision-making agents. Guaranteeing performance of such human-cyber-physical systems will require predictive mathematical models of this dynamic coupling. Toward this end, we propose a rapprochement between robotics and neuromechanics premised on the existence of internal forward and inverse models in the human agent. We hypothesize that, in tele-robotic applications of interest, a human operator learns to invert automation dynamics, directly translating from desired task to required control input. By formulating the model inversion problem in the context of a tracking task for a nonlinear control system in control-a_ne form, we derive criteria for exponential tracking and show that the resulting dynamic inverse model generally renders a portion of the physical system state (i.e., the internal dynamics) unobservable from the human operator's perspective. Under stability conditions, we show that the human can achieve exponential tracking without formulating an estimate of the system's state so long as they possess an accurate model of the system's dynamics. These theoretical results are illustrated using a planar quadrotor example. We then demonstrate that the automation can intervene to improve performance of the tracking task by solving an optimal control problem. Performance is guaranteed to improve under the assumption that the human learns and inverts the dynamic model of the altered system. We conclude with a discussion of practical limitations that may hinder exact dynamic model inversion.

  10. Human visual performance model for crewstation design

    Science.gov (United States)

    Larimer, James; Prevost, Michael; Arditi, Aries; Azueta, Steven; Bergen, James; Lubin, Jeffrey

    1991-01-01

    An account is given of a Visibility Modeling Tool (VMT) which furnishes a crew-station designer with the means to assess configurational tradeoffs, with a view to the impact of various options on the unambiguous access of information to the pilot. The interactive interface of the VMT allows the manipulation of cockpit geometry, ambient lighting, pilot ergonomics, and the displayed symbology. Performance data can be displayed in the form of 3D contours into the crewstation graphic model, thereby yielding an indication of the operator's visual capabilities.

  11. Companion animals symposium: humanized animal models of the microbiome.

    Science.gov (United States)

    Gootenberg, D B; Turnbaugh, P J

    2011-05-01

    Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.

  12. Evaluation of human thorax FE model in various impact scenarios

    Directory of Open Access Journals (Sweden)

    Jansová M.

    2015-06-01

    Full Text Available The study focused on the validation of the 50th percentile male model — a detailed FE model of the thoracic segment of the human body developed within project Development of a Finite Element Model of the Human Thorax and Upper Extremities (THOMO co-funded by the European Commission (7th Framework Programme. The model response was tested in three impact scenarios: frontal, lateral and oblique. The resulting impactor contact force vs. time and chest deflection vs. time responses were compared with experimental results. The strain profile of the 5th rib was checked with lateral and oblique strain profiles from post-mortem human subject (PMHS experiments. The influence of heart and lungs on the mechanical response of the model was assessed and the material data configuration, giving the most biofidelic thorax behaviour, was identified.

  13. Complex human activities recognition using interval temporal syntactic model

    Institute of Scientific and Technical Information of China (English)

    夏利民; 韩芬; 王军

    2016-01-01

    A novel method based on interval temporal syntactic model was proposed to recognize human activities in video flow. The method is composed of two parts: feature extract and activities recognition. Trajectory shape descriptor, speeded up robust features (SURF) and histograms of optical flow (HOF) were proposed to represent human activities, which provide more exhaustive information to describe human activities on shape, structure and motion. In the process of recognition, a probabilistic latent semantic analysis model (PLSA) was used to recognize sample activities at the first step. Then, an interval temporal syntactic model, which combines the syntactic model with the interval algebra to model the temporal dependencies of activities explicitly, was introduced to recognize the complex activities with a time relationship. Experiments results show the effectiveness of the proposed method in comparison with other state-of-the-art methods on the public databases for the recognition of complex activities.

  14. Fungal contaminants in cytopathology specimens

    Directory of Open Access Journals (Sweden)

    Prashant Sharma

    2014-02-01

    Full Text Available A pseudo-epidemic of environmental fungi, most likely by Fusarium spp., leading to inappropriate investigations for disseminated systemic mycosis is described. Subtle diagnostic clues, including the specimens affected, the nature of the host response, and the type of fungal elements noted helped to determine the nature of contaminants. The potential pitfall can be avoided by the knowledge of pertinent disease biology, prompt consultation for infectious diseases, and investigations of the potential environmental sources followed by source control.

  15. Optimization and validation of a quantitative liquid chromatography-tandem mass spectrometric method covering 295 bacterial and fungal metabolites including all regulated mycotoxins in four model food matrices.

    Science.gov (United States)

    Malachová, Alexandra; Sulyok, Michael; Beltrán, Eduardo; Berthiller, Franz; Krska, Rudolf

    2014-10-01

    An LC-MS/MS "dilute and shoot" method for the determination of 295 fungal and bacterial metabolites was optimized and validated according to the guidelines established in the Directorate General for Health and Consumer Affairs of the European Commission (SANCO) document No. 12495/2011. Four different types of food matrices were chosen for validation: apple puree for infants (high water content), hazelnuts (high fat content), maize (high starch and low fat content) and green pepper (difficult or unique matrix). Method accuracy and precision was evaluated using spiked samples in five replicates at two concentration levels. Method trueness was demonstrated through participation in various proficiency tests. Although the method covers a total number of 331 analytes, validation data were acquired only for 295 analytes, either due to the non-availability of analytical standards or due other reasons described in this paper. Concerning the apparent recovery, the percentage of 295 analytes matching the acceptable recovery range of 70-120% lied down by SANCO varied from 21% in green pepper to 74% in apple puree at the highest spiking level. At the levels close to limit of quantification only 20-58% of the analytes fulfilled this criterion. The extent of matrix effects was strongly dependent on the analyte/matrix combination. In general, the lowest matrix effects were observed in apple puree (59% of analytes were not influenced by enhancement/suppression at all at the highest validation level). The highest matrix effects were observed in green pepper, where only 10% of analytes did not suffer from signal suppression/enhancement. The repeatability of the method was acceptable (RSD≤20) for 97% of all analytes in apple puree and hazelnuts, for 95% in maize and for 89% in green pepper. Concerning the trueness of the method, Z-scores were generally between -2 and 2, despite a broad variety of different matrices. Based on these results it can be concluded that quantitative

  16. Paralysis recovery in humans and model systems

    Science.gov (United States)

    Edgerton, V. Reggie; Roy, Roland R.

    2002-01-01

    Considerable evidence now demonstrates that extensive functional and anatomical reorganization following spinal cord injury occurs in centers of the brain that have some input into spinal motor pools. This is very encouraging, given the accumulating evidence that new connections formed across spinal lesions may not be initially functionally useful. The second area of advancement in the field of paralysis recovery is in the development of effective interventions to counter axonal growth inhibition. A third area of significant progress is the development of robotic devices to quantify the performance level of motor tasks following spinal cord injury and to 'teach' the spinal cord to step and stand. Advances are being made with robotic devices for mice, rats and humans.

  17. Vibration analysis with MADYMO human models

    NARCIS (Netherlands)

    Verver, M.M.; Hoof, J.F.A.M. van

    2002-01-01

    The importance of comfort for the automotive industry is increasing. Car manufacturers use comfort to distinguish their products from their competitors. However, the development and design of a new car seat or interior is very time consuming and expensive. The introduction of computer models of huma

  18. Modeling human disease using organotypic cultures

    DEFF Research Database (Denmark)

    Schweiger, Pawel J; Jensen, Kim B

    2016-01-01

    Reliable disease models are needed in order to improve quality of healthcare. This includes gaining better understanding of disease mechanisms, developing new therapeutic interventions and personalizing treatment. Up-to-date, the majority of our knowledge about disease states comes from in vivo...

  19. An experimental study of human birth models

    Science.gov (United States)

    Baumer, Alexa; Gossmann, Roseanna; Fauci, Lisa J.; Leftwich, Megan C.

    2016-11-01

    The laboring uterus is a complex and dynamic fluid system. Relatively little is known about the fluid properties in this system. However, the two primary fluids of interest, amniotic fluid and vernix caseosa, likely play integral roles in the force transferred to the fetus during the final stages of parturition. This investigation probes the role of fluid in the force transfer during delivery by considering physical models that determine the role of various components of the full system. The first experimental model represents the fetus passing through the birth canal as concentric cylinders with a fluid filled gap. The rigid, inner cylinder moves through the highly flexible outer cylinder at a prescribed velocity. The geometry of the inner cylinder is varied by aspect ratio and length. A total of five different inner geometries are used to fully investigate the parameter space. As the inner cylinder moves through the outer cylinder, strain measurements are taken. These measurements are converted to force measurements as a function of time and position in the outer cylinder. The results of these experiments are compared with numerical results to form a more complete picture of force transfer. This model can be used as the foundation for predicting the force needed to deliver a fetus in the final stages of parturition. Additionally, more complex models, that incorporate uterine contraction forces, are being developed.

  20. Modeling Human Aesthetic Perception of Visual Textures

    NARCIS (Netherlands)

    Thumfart, Stefan; Jacobs, Richard H. A. H.; Lughofer, Edwin; Eitzinger, Christian; Cornelissen, Frans W.; Groissboeck, Werner; Richter, Roland

    2011-01-01

    Texture is extensively used in areas such as product design and architecture to convey specific aesthetic information. Using the results of a psychological experiment, we model the relationship between computational texture features and aesthetic properties of visual textures. Contrary to previous a

  1. Animal model of human disease. Multiple myeloma

    NARCIS (Netherlands)

    Radl, J.; Croese, J.W.; Zurcher, C.; Enden-Vieveen, M.H.M. van den; Leeuw, A.M. de

    1988-01-01

    Animal models of spontaneous and induced plasmacytomas in some inbred strains of mice have proven to be useful tools for different studies on tumorigenesis and immunoregulation. Their wide applicability and the fact that after their intravenous transplantation, the recipient mice developed bone

  2. Modeling Human Aesthetic Perception of Visual Textures

    NARCIS (Netherlands)

    Thumfart, Stefan; Jacobs, Richard H. A. H.; Lughofer, Edwin; Eitzinger, Christian; Cornelissen, Frans W.; Groissboeck, Werner; Richter, Roland

    2011-01-01

    Texture is extensively used in areas such as product design and architecture to convey specific aesthetic information. Using the results of a psychological experiment, we model the relationship between computational texture features and aesthetic properties of visual textures. Contrary to previous

  3. A human experimental model of episodic pain

    DEFF Research Database (Denmark)

    Petrini, Laura; Hennings, Kristian; Li, Xi

    2014-01-01

    An experimental model of daily episodic pain was developed to investigate peripheral sensitization and cortical reorganization in healthy individuals. Two experiments (A and B) were conducted. Experiments A and B consisted of one and five consecutive days, respectively, in which the participants ...

  4. Fungal genome resources at NCBI.

    Science.gov (United States)

    Robbertse, B; Tatusova, T

    2011-09-01

    The National Center for Biotechnology Information (NCBI) is well known for the nucleotide sequence archive, GenBank and sequence analysis tool BLAST. However, NCBI integrates many types of biomolecular data from variety of sources and makes it available to the scientific community as interactive web resources as well as organized releases of bulk data. These tools are available to explore and compare fungal genomes. Searching all databases with Fungi [organism] at http://www.ncbi.nlm.nih.gov/ is the quickest way to find resources of interest with fungal entries. Some tools though are resources specific and can be indirectly accessed from a particular database in the Entrez system. These include graphical viewers and comparative analysis tools such as TaxPlot, TaxMap and UniGene DDD (found via UniGene Homepage). Gene and BioProject pages also serve as portals to external data such as community annotation websites, BioGrid and UniProt. There are many different ways of accessing genomic data at NCBI. Depending on the focus and goal of research projects or the level of interest, a user would select a particular route for accessing genomic databases and resources. This review article describes methods of accessing fungal genome data and provides examples that illustrate the use of analysis tools.

  5. FungiQuant: A broad-coverage fungal quantitative real-time PCR assay

    Directory of Open Access Journals (Sweden)

    Liu Cindy M

    2012-11-01

    Full Text Available Abstract Background Fungal load quantification is a critical component of fungal community analyses. Limitation of current approaches for quantifying the fungal component in the human microbiome suggests the need for new broad-coverage techniques. Methods We analyzed 2,085 18S rRNA gene sequences from the SILVA database for assay design. We generated and quantified plasmid standards using a qPCR-based approach. We evaluated assay coverage against 4,968 sequences and performed assay validation following the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE guidelines. Results We designed FungiQuant, a TaqMan® qPCR assay targeting a 351 bp region in the fungal 18S rRNA gene. Our in silico analysis showed that FungiQuant is a perfect sequence match to 90.0% of the 2,617 fungal species analyzed. We showed that FungiQuant’s is 100% sensitive and its amplification efficiencies ranged from 76.3% to 114.5%, with r2-values of >0.99 against the 69 fungal species tested. Additionally, FungiQuant inter- and intra-run coefficients of variance ranged from Conclusions FungiQuant has comprehensive coverage against diverse fungi and is a robust quantification and detection tool for delineating between true fungal detection and non-target human DNA.

  6. Fungal melanins differ in planar stacking distances.

    Science.gov (United States)

    Casadevall, Arturo; Nakouzi, Antonio; Crippa, Pier R; Eisner, Melvin

    2012-01-01

    Melanins are notoriously difficult to study because they are amorphous, insoluble and often associated with other biological materials. Consequently, there is a dearth of structural techniques to study this enigmatic pigment. Current models of melanin structure envision the stacking of planar structures. X ray diffraction has historically been used to deduce stacking parameters. In this study we used X ray diffraction to analyze melanins derived from Cryptococcus neoformans, Aspergillus niger, Wangiella dermatitides and Coprinus comatus. Analysis of melanin in melanized C. neoformans encapsulated cells was precluded by the fortuitous finding that the capsular polysaccharide had a diffraction spectrum that was similar to that of isolated melanin. The capsular polysaccharide spectrum was dominated by a broad non-Bragg feature consistent with origin from a repeating structural motif that may arise from inter-molecular interactions and/or possibly gel organization. Hence, we isolated melanin from each fungal species and compared diffraction parameters. The results show that the inferred stacking distances of fungal melanins differ from that reported for synthetic melanin and neuromelanin, occupying intermediate position between these other melanins. These results suggest that all melanins have a fundamental diffracting unit composed of planar graphitic assemblies that can differ in stacking distance. The stacking peak appears to be a distinguishing universal feature of melanins that may be of use in characterizing these enigmatic pigments.

  7. Lumped parametric model of the human ear for sound transmission.

    Science.gov (United States)

    Feng, Bin; Gan, Rong Z

    2004-09-01

    A lumped parametric model of the human auditoria peripherals consisting of six masses suspended with six springs and ten dashpots was proposed. This model will provide the quantitative basis for the construction of a physical model of the human middle ear. The lumped model parameters were first identified using published anatomical data, and then determined through a parameter optimization process. The transfer function of the middle ear obtained from human temporal bone experiments with laser Doppler interferometers was used for creating the target function during the optimization process. It was found that, among 14 spring and dashpot parameters, there were five parameters which had pronounced effects on the dynamic behaviors of the model. The detailed discussion on the sensitivity of those parameters was provided with appropriate applications for sound transmission in the ear. We expect that the methods for characterizing the lumped model of the human ear and the model parameters will be useful for theoretical modeling of the ear function and construction of the ear physical model.

  8. Nosocomial fungal infections: candidemia.

    Science.gov (United States)

    Verduyn Lunel, F M; Meis, J F; Voss, A

    1999-07-01

    Candida species are frequently encountered as part of the human commensal flora. Colonization mostly precedes candidemia and is an independent risk factor for the development of candidemia. Genotyping methods showed the similarity between colonizing and infecting strains, thus making endogenous origin likely, though exogenous sources like total parenteral nutrition also have been described. Health care workers (HCWs) play an important role in the transmission of yeasts. Candida species are frequently isolated from the hands of HCWs and can be transmitted from hands to patients. Granulocytopenia and damage of the mucosal lining resulting from intensive chemotherapy due to cancer, the increasing use of broad spectrum antibiotics, and the use of intravenous catheters are other important risk factors for the development of candidemia. Candidemia is associated with a high mortality and prolonged hospitalization. Therefore, and because of the high frequency of dissemination, all candidemias should be treated. Amphotericin B was considered the standard drug for the systemic treatment of candidemia. Fluconazole has been shown to be an effective and safe alternative in non-neutropenic patients. 5-Fluorocytosine has been used in combination with amphotericin B in the treatment of deep-seated infections. Liposomal formulations of amphotericin B and other new antifungal drugs currently are under investigation. C. albicans is the most frequently isolated Candida species, although the proportion of infections caused by non-C. albicans species is increasing. Also, there are reports of development of resistance to amphotericin B. C. lusitaniae is known for primary resistance and the development of resistance to amphotericin B. Development of resistance to fluconazole is mainly seen in AIDS patients with recurrent oropharyngeal candidiasis who receive longer courses of therapy.

  9. Identification and comparative analysis of sixteen fungal peptidyl-prolyl cis/trans isomerase repertoires

    Directory of Open Access Journals (Sweden)

    Pemberton Trevor J

    2006-09-01

    Full Text Available Abstract Background The peptidyl-prolyl cis/trans isomerase (PPIase class of proteins is present in all known eukaryotes, prokaryotes, and archaea, and it is comprised of three member families that share the ability to catalyze the cis/trans isomerisation of a prolyl bond. Some fungi have been used as model systems to investigate the role of PPIases within the cell, however how representative these repertoires are of other fungi or humans has not been fully investigated. Results PPIase numbers within these fungal repertoires appears associated with genome size and orthology between repertoires was found to be low. Phylogenetic analysis showed the single-domain FKBPs to evolve prior to the multi-domain FKBPs, whereas the multi-domain cyclophilins appear to evolve throughout cyclophilin evolution. A comparison of their known functions has identified, besides a common role within protein folding, multiple roles for the cyclophilins within pre-mRNA splicing and cellular signalling, and within transcription and cell cycle regulation for the parvulins. However, no such commonality was found with the FKBPs. Twelve of the 17 human cyclophilins and both human parvulins, but only one of the 13 human FKBPs, identified orthologues within these fungi. hPar14 orthologues were restricted to the Pezizomycotina fungi, and R. oryzae is unique in the known fungi in possessing an hCyp33 orthologue and a TPR-containing FKBP. The repertoires of Cryptococcus neoformans, Aspergillus fumigatus, and Aspergillus nidulans were found to exhibit the highest orthology to the human repertoire, and Saccharomyces cerevisiae one of the lowest. Conclusion Given this data, we would hypothesize that: (i the evolution of the fungal PPIases is driven, at least in part, by the size of the proteome, (ii evolutionary pressures differ both between the different PPIase families and the different fungi, and (iii whilst the cyclophilins and parvulins have evolved to perform conserved

  10. Modeling and remote sensing of human induced water cycle change

    Science.gov (United States)

    Pokhrel, Yadu N.

    2016-04-01

    The global water cycle has been profoundly affected by human land-water management especially during the last century. Since the changes in water cycle can affect the functioning of a wide range of biophysical and biogeochemical processes of the Earth system, it is essential to account for human land-water management in land surface models (LSMs) which are used for water resources assessment and to simulate the land surface hydrologic processes within Earth system models (ESMs). During the last two decades, noteworthy progress has been made in modeling human impacts on the water cycle but sufficient advancements have not yet been made, especially in representing human factors in large-scale LSMs toward integrating them into ESMs. In this study, an integrated modeling framework of continental-scale water cycle, with explicit representation of climate and human induced forces (e.g., irrigation, groundwater pumping) is developed and used to reconstruct the observed water cycle changes in the past and to attribute the observed changes to climatic and human factors. The new model builds upon two different previously developed models: a global LSM called the Human Impacts and GroundWater in the MATSIRO (HiGW-MAT) and a high-resolution regional groundwater model called the LEAF-Hydro-Flood. The model is used to retro-simulate the hydrologic stores and fluxes in close dialogue with in-situ and GRACE satellite based observations at a wide range of river basin scales around the world, with a particular focus on the changes in groundwater dynamics in northwest India, Pakistan, and the High Plains and Central Valley aquifers in the US.

  11. Human pluripotent stem cells: an emerging model in developmental biology.

    Science.gov (United States)

    Zhu, Zengrong; Huangfu, Danwei

    2013-02-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development 'in a dish'. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development.

  12. Modeling Human Blockers in Millimeter Wave Radio Links

    Institute of Scientific and Technical Information of China (English)

    Jonathan S. Lu; Daniel Steinbach; Patrick Cabrol; Philip Pietraski

    2012-01-01

    In this paper, we investigate the loss caused by multiple humans blocking millimeter wave frequencies. We model human blockers as absorbing screens of infinite height with two knife-edges, We take a physical optics approach to computing the diffraction around the absorbing screens, This approach differs to the geometric optics approach described in much of the literature. The blocking model is validated by measuring the gain from multiple-human blocking configurations on an indoor link. The blocking gains predicted using Piazzi ' s numerical integration method (a physical optics method) agree well with measurements taken from approximately 2.7 dB to -50 dB. Thereofre, this model is suitable for real human blockers, The mean prediction error for the method is approximately -1.2 dB, and the standard deviation is approximately 5 dB.

  13. A novel polar-based human face recognition computational model

    Directory of Open Access Journals (Sweden)

    Y. Zana

    2009-07-01

    Full Text Available Motivated by a recently proposed biologically inspired face recognition approach, we investigated the relation between human behavior and a computational model based on Fourier-Bessel (FB spatial patterns. We measured human recognition performance of FB filtered face images using an 8-alternative forced-choice method. Test stimuli were generated by converting the images from the spatial to the FB domain, filtering the resulting coefficients with a band-pass filter, and finally taking the inverse FB transformation of the filtered coefficients. The performance of the computational models was tested using a simulation of the psychophysical experiment. In the FB model, face images were first filtered by simulated V1- type neurons and later analyzed globally for their content of FB components. In general, there was a higher human contrast sensitivity to radially than to angularly filtered images, but both functions peaked at the 11.3-16 frequency interval. The FB-based model presented similar behavior with regard to peak position and relative sensitivity, but had a wider frequency band width and a narrower response range. The response pattern of two alternative models, based on local FB analysis and on raw luminance, strongly diverged from the human behavior patterns. These results suggest that human performance can be constrained by the type of information conveyed by polar patterns, and consequently that humans might use FB-like spatial patterns in face processing.

  14. Generation and use of human 3D-CAD models

    Science.gov (United States)

    Grotepass, Juergen; Speyer, Hartmut; Kaiser, Ralf

    2002-05-01

    Individualized Products are one of the ten mega trends of the 21st Century with human modeling as the key issue for tomorrow's design and product development. The use of human modeling software for computer based ergonomic simulations within the production process increases quality while reducing costs by 30- 50 percent and shortening production time. This presentation focuses on the use of human 3D-CAD models for both, the ergonomic design of working environments and made to measure garment production. Today, the entire production chain can be designed, individualized models generated and analyzed in 3D computer environments. Anthropometric design for ergonomics is matched to human needs, thus preserving health. Ergonomic simulation includes topics as human vision, reachability, kinematics, force and comfort analysis and international design capabilities. In German more than 17 billions of Mark are moved to other industries, because clothes do not fit. Individual clothing tailored to the customer's preference means surplus value, pleasure and perfect fit. The body scanning technology is the key to generation and use of human 3D-CAD models for both, the ergonomic design of working environments and made to measure garment production.

  15. Modeling aspects of human memory for scientific study.

    Energy Technology Data Exchange (ETDEWEB)

    Caudell, Thomas P. (University of New Mexico); Watson, Patrick (University of Illinois - Champaign-Urbana Beckman Institute); McDaniel, Mark A. (Washington University); Eichenbaum, Howard B. (Boston University); Cohen, Neal J. (University of Illinois - Champaign-Urbana Beckman Institute); Vineyard, Craig Michael; Taylor, Shawn Ellis; Bernard, Michael Lewis; Morrow, James Dan; Verzi, Stephen J.

    2009-10-01

    Working with leading experts in the field of cognitive neuroscience and computational intelligence, SNL has developed a computational architecture that represents neurocognitive mechanisms associated with how humans remember experiences in their past. The architecture represents how knowledge is organized and updated through information from individual experiences (episodes) via the cortical-hippocampal declarative memory system. We compared the simulated behavioral characteristics with those of humans measured under well established experimental standards, controlling for unmodeled aspects of human processing, such as perception. We used this knowledge to create robust simulations of & human memory behaviors that should help move the scientific community closer to understanding how humans remember information. These behaviors were experimentally validated against actual human subjects, which was published. An important outcome of the validation process will be the joining of specific experimental testing procedures from the field of neuroscience with computational representations from the field of cognitive modeling and simulation.

  16. Advances in targeting the vacuolar proton-translocating ATPase (V-ATPase) for anti-fungal therapy

    Science.gov (United States)

    Hayek, Summer R.; Lee, Samuel A.; Parra, Karlett J.

    2014-01-01

    Vacuolar proton-translocating ATPase (V-ATPase) is a membrane-bound, multi-subunit enzyme that uses the energy of ATP hydrolysis to pump protons across membranes. V-ATPase activity is critical for pH homeostasis and organelle acidification as well as for generation of the membrane potential that drives secondary transporters and cellular metabolism. V-ATPase is highly conserved across species and is best characterized in the model fungus Saccharomyces cerevisiae. However, recent studies in mammals have identified significant alterations from fungi, particularly in the isoform composition of the 14 subunits and in the regulation of complex disassembly. These differences could be exploited for selectivity between fungi and humans and highlight the potential for V-ATPase as an anti-fungal drug target. Candida albicans is a major human fungal pathogen and causes fatality in 35% of systemic infections, even with anti-fungal treatment. The pathogenicity of C. albicans correlates with environmental, vacuolar, and cytoplasmic pH regulation, and V-ATPase appears to play a fundamental role in each of these processes. Genetic loss of V-ATPase in pathogenic fungi leads to defective virulence, and a comprehensive picture of the mechanisms involved is emerging. Recent studies have explored the practical utility of V-ATPase as an anti-fungal drug target in C. albicans, including pharmacological inhibition, azole therapy, and targeting of downstream pathways. This overview will discuss these studies as well as hypothetical ways to target V-ATPase and novel high-throughput methods for use in future drug discovery screens. PMID:24478704

  17. Advances in targeting the vacuolar proton-translocating ATPase (V-ATPase for anti-fungal therapy

    Directory of Open Access Journals (Sweden)

    Summer R. Hayek

    2014-01-01

    Full Text Available Vacuolar proton-translocating ATPase (V-ATPase is a membrane-bound, multi-subunit enzyme that uses the energy of ATP hydrolysis to pump protons across membranes. V-ATPase activity is critical for pH homeostasis and organelle acidification as well as for generation of the membrane potential that drives secondary transporters and cellular metabolism. V-ATPase is highly conserved across species and is best characterized in the model fungus Saccharomyces cerevisiae (S. cerevisiae. However, recent studies in mammals have identified significant alterations from fungi, particularly in the isoform composition of the 14 subunits and in the regulation of complex disassembly. These differences could be exploited for selectivity between fungi and humans and highlight the potential for V-ATPase as an anti-fungal drug target. Candida albicans (C. albicans is a major human fungal pathogen and causes fatality in 35% of systemic infections, even with anti-fungal treatment. The pathogenicity of C. albicans correlates with environmental, vacuolar, and cytoplasmic pH regulation, and V-ATPase appears to play a fundamental role in each of these processes. Genetic loss of V-ATPase in pathogenic fungi leads to defective virulence, and a comprehensive picture of the mechanisms involved is emerging. Recent studies have explored the practical utility of V-ATPase as an anti-fungal drug target in C. albicans, including pharmacological inhibition, azole therapy, and targeting of downstream pathways. This overview will discuss these studies as well as hypothetical ways to target V-ATPase and novel high-throughput methods for use in future drug discovery screens.

  18. 3D virtual human rapid modeling method based on top-down modeling mechanism

    Directory of Open Access Journals (Sweden)

    LI Taotao

    2017-01-01

    Full Text Available Aiming to satisfy the vast custom-made character demand of 3D virtual human and the rapid modeling in the field of 3D virtual reality, a new virtual human top-down rapid modeling method is put for-ward in this paper based on the systematic analysis of the current situation and shortage of the virtual hu-man modeling technology. After the top-level realization of virtual human hierarchical structure frame de-sign, modular expression of the virtual human and parameter design for each module is achieved gradu-al-level downwards. While the relationship of connectors and mapping restraints among different modules is established, the definition of the size and texture parameter is also completed. Standardized process is meanwhile produced to support and adapt the virtual human top-down rapid modeling practice operation. Finally, the modeling application, which takes a Chinese captain character as an example, is carried out to validate the virtual human rapid modeling method based on top-down modeling mechanism. The result demonstrates high modelling efficiency and provides one new concept for 3D virtual human geometric mod-eling and texture modeling.

  19. REMOVAL OF ARSENIC FROM AN AQUEOUS SOLUTION BY PRETREATED WASTE TEA FUNGAL BIOMASS

    Directory of Open Access Journals (Sweden)

    S. Mamisahebei , Gh. R. Jahed Khaniki, A. Torabian, S. Nasseri, K. Naddafi

    2007-04-01

    Full Text Available Arsenic contamination in water poses a serious threat on human health. The tea fungus known as Kombucha is a waste produced during black tea fermentation. The objective of this study was to examine the main aspect of a possible strategy for the removal of arsenates employing tea fungal biomass. The pretreatment of biomass with FeCl3 was found to improve the biosorption efficiency. Arsenics uptake was found to be rapid for all concentrations and reached to 79% of equilibrium capacity of biosorption in 20 min and reached equilibrium in 90 min. The pseudo second-order and first-order models described the biosorption kinetics of As (V with good correlation coefficient (R2>0.93 and better than the other equations. The data obtained from the experiment of biosorption isotherm were analyzed using the Freundlich and Langmuir isotherm models. The equation described the isotherm of As (V biosorption with relatively high correlation coefficient (R2>0.93. According to the Langmuir model, the maximum uptake capacities (qm of tea fungal biomass for As (V were obtained 3.9810-3 mmol/gr. The effect of Na+, K+, Mg+2 and Ca+2 on equilibrium capacities of As was not significant. The variation of sorption efficiency with pH showed that optimum biosorption takes place in the pH ranges of 6 to 8. Promising results were obtained in laboratory experiments and effective As (V removals were observed.

  20. Tenebrio molitor (Coleoptera: Tenebrionidae) as an alternative host to study fungal infections.

    Science.gov (United States)

    de Souza, Patrícia Canteri; Morey, Alexandre Tadachi; Castanheira, Gabriel Marcondes; Bocate, Karla Paiva; Panagio, Luciano Aparecido; Ito, Fabio Augusto; Furlaneto, Márcia Cristina; Yamada-Ogatta, Sueli Fumie; Costa, Idessânia Nazareth; Mora-Montes, Hector Manuel; Almeida, Ricardo Sergio

    2015-11-01

    Models of host–pathogen interactions are crucial for the analysis of microbial pathogenesis. In this context, invertebrate hosts, including Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode) and Galleria mellonella (moth), have been used to study the pathogenesis of fungi and bacteria. Each of these organisms offers distinct benefits in elucidating host–pathogen interactions. In this study,we present a newinvertebrate infection model to study fungal infections: the Tenebrio molitor (beetle) larvae. Here we performed T. molitor larvae infection with one of two important fungal human pathogens, Candida albicans or Cryptococcus neoformans, and analyzed survival curves and larva infected tissues.We showed that increasing concentrations of inoculum of both fungi resulted in increased mortality rates, demonstrating the efficiency of the method to evaluate the virulence of pathogenic yeasts. Additionally, following 12 h post-infection, C. albicans formsmycelia, spreading its hyphae through the larva tissue,whilst GMS stain enabled the visualization of C. neoformans yeast and theirmelanin capsule. These larvae are easier to cultivate in the laboratory than G. mellonella larvae, and offer the same benefits. Therefore, this insect model could be a useful alternative tool to screen clinical pathogenic yeast strainswith distinct virulence traits or different mutant strains.