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Sample records for human septins implications

  1. A draft of the human septin interactome.

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    Marcel Nakahira

    Full Text Available BACKGROUND: Septins belong to the GTPase superclass of proteins and have been functionally implicated in cytokinesis and the maintenance of cellular morphology. They are found in all eukaryotes, except in plants. In mammals, 14 septins have been described that can be divided into four groups. It has been shown that mammalian septins can engage in homo- and heterooligomeric assemblies, in the form of filaments, which have as a basic unit a hetero-trimeric core. In addition, it has been speculated that the septin filaments may serve as scaffolds for the recruitment of additional proteins. METHODOLOGY/PRINCIPAL FINDINGS: Here, we performed yeast two-hybrid screens with human septins 1-10, which include representatives of all four septin groups. Among the interactors detected, we found predominantly other septins, confirming the tendency of septins to engage in the formation of homo- and heteropolymeric filaments. CONCLUSIONS/SIGNIFICANCE: If we take as reference the reported arrangement of the septins 2, 6 and 7 within the heterofilament, (7-6-2-2-6-7, we note that the majority of the observed interactions respect the "group rule", i.e. members of the same group (e.g. 6, 8, 10 and 11 can replace each other in the specific position along the heterofilament. Septins of the SEPT6 group preferentially interacted with septins of the SEPT2 group (p<0.001, SEPT3 group (p<0.001 and SEPT7 group (p<0.001. SEPT2 type septins preferentially interacted with septins of the SEPT6 group (p<0.001 aside from being the only septin group which interacted with members of its own group. Finally, septins of the SEPT3 group interacted preferentially with septins of the SEPT7 group (p<0.001. Furthermore, we found non-septin interactors which can be functionally attributed to a variety of different cellular activities, including: ubiquitin/sumoylation cycles, microtubular transport and motor activities, cell division and the cell cycle, cell motility, protein

  2. Septin mutations in human cancers

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    Elias T Spiliotis

    2016-11-01

    Full Text Available Septins are GTP-binding proteins that are evolutionarily and structurally related to the RAS oncogenes. Septin expression levels are altered in many cancers and new advances point to how abnormal septin expression may contribute to the progression of cancer. In contrast to the RAS GTPases, which are frequently mutated and actively promote tumorigenesis, little is known about the occurrence and role of septin mutations in human cancers. Here, we review septin missense mutations that are currently in the Catalog of Somatic Mutations in Cancer (COSMIC database. The majority of septin mutations occur in tumors of the large intestine, skin, endometrium and stomach. Over 25% of the annotated mutations in SEPT2, SEPT4 and SEPT9 belong to large intestine tumors. From all septins, SEPT9 and SEPT14 exhibit the highest mutation frequencies in skin, stomach and large intestine cancers. While septin mutations occur with frequencies lower than 3%, recurring mutations in several invariant and highly conserved amino acids are found across different septin paralogs and tumor types. Interestingly, a significant number of these mutations occur in the GTP-binding pocket and septin dimerization interfaces. Future studies may determine how these somatic mutations affect septin structure and function, whether they contribute to the progression of specific cancers and if they could serve as tumor-specific biomarkers.

  3. The human septin7 and the yeast CDC10 septin prevent Bax and copper mediated cell death in yeast.

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    Horowitz, Avital; Lapointe, Jason F; Eid, Rawan; Sheibani, Sara; Gharib, Nada; Jones, Natalie K; Vali, Hojatollah; Mandato, Craig A; Greenwood, Michael T

    2013-12-01

    The mechanisms of programmed cell death activate genetically encoded intracellular programs in a controlled manner, the most common form being apoptosis. Apoptosis is carried out through a cascade of caspase mediated proteolytic cleavages initiated by the oligomerization of Bax, a cardinal regulator of mitochondrial-mediated apoptosis. Heterologous expression of Bax in yeast causes cell death that shares a number of similarities to processes that occur in mammalian apoptosis. A screen of a cardiac cDNA library for suppressors of Bax-mediated apoptosis identified human septin7, a protein that belongs to the septin superfamily of conserved GTP-binding proteins that share a conserved cdc/septin domain. Analysis of the amino acid sequence deduced from the septin7 clone as well as the corresponding human septin7 gene revealed that a novel alternatively spliced transcript called septin7 variant4 (v4) was uncovered. Yeast cells overexpressing the human septin7 v4 cDNA were also capable of resisting copper-mediated cell death suggesting that it is not only a Bax suppressor but also an anti-apoptotic sequence. Analysis of septin7 function in a MCA1Δ yeast strain suggests that septin7 inhibits apoptosis in a caspase independent pathway. Overexpression of the yeast septin7 ortholog CDC10 also conferred resistance to the negative effects of copper as well as protecting cells from the overexpression of Bax. In contrast, septin7 was unable to prevent the increase in cell size associated with mutants lacking the endogenous yeast CDC10 gene. Taken together, our analysis suggests that anti-apoptosis is a novel yet evolutionarily conserved property of the septin7 sub-family of septins.

  4. Purification of recombinant human and Drosophila septin hexamers for TIRF assays of actin-septin filament assembly.

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    Mavrakis, M; Tsai, F-C; Koenderink, G H

    2016-01-01

    Septins are guanine nucleotide-binding proteins that are conserved from fungi to humans. Septins assemble into heterooligomeric complexes and higher-order structures with key roles in various cellular functions including cell migration and division. The mechanisms by which septins assemble and interact with other cytoskeletal elements like actin remain elusive. A powerful approach to address this question is by cell-free reconstitution of purified cytoskeletal proteins combined with fluorescence microscopy. Here, we describe procedures for the purification of recombinant Drosophila and human septin hexamers from Escherichia coli and reconstitution of actin-septin coassembly. These procedures can be used to compare assembly of Drosophila and human septins and their coassembly with the actin cytoskeleton by total internal reflection fluorescence microscopy.

  5. Human septin isoforms and the GDP-GTP cycle.

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    Zent, Eldar; Wittinghofer, Alfred

    2014-02-01

    Septins form oligomeric complexes consisting of septins from different subgroups, which form filaments that are involved in a number of biological processes. They are GTP-binding proteins that contain all the necessary elements to perform the general GDP-to-GTP conformational switch. It is however unclear whether or not such a switch is important for the dynamics of septin filaments. Here we investigate the complex GTPase reaction of members of each of the four human septin groups, which is dominated by the stability of dimer formation via the nucleotide binding or so-called G-interface. The results also show that the actual hydrolysis reaction is very similar for three septin groups in the monomeric state while the Sept6 has no GTPase activity. Sept7, the only member of the Sept7 subgroup, forms a very tight G-interface dimer in the GDP-bound state. Here we show that the stability of the interface is dramatically decreased by exchanging GDP with a nucleoside triphosphate, which is believed to influence filament formation and dynamics via Sept7.

  6. The Mammalian Septin Interactome

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    Neubauer, Katharina; Zieger, Barbara

    2017-01-01

    Septins are GTP-binding and membrane-interacting proteins with a highly conserved domain structure involved in various cellular processes, including cytoskeleton organization, cytokinesis, and membrane dynamics. To date, 13 different septin genes have been identified in mammals (SEPT1 to SEPT12 and SEPT14), which can be classified into four distinct subgroups based on the sequence homology of their domain structure (SEPT2, SEPT3, SEPT6, and SEPT7 subgroup). The family members of these subgroups have a strong affinity for other septins and form apolar tri-, hexa-, or octameric complexes consisting of multiple septin polypeptides. The first characterized core complex is the hetero-trimer SEPT2-6-7. Within these complexes single septins can be exchanged in a subgroup-specific manner. Hexamers contain SEPT2 and SEPT6 subgroup members and SEPT7 in two copies each whereas the octamers additionally comprise two SEPT9 subgroup septins. The various isoforms seem to determine the function and regulation of the septin complex. Septins self-assemble into higher-order structures, including filaments and rings in orders, which are typical for different cell types. Misregulation of septins leads to human diseases such as neurodegenerative and bleeding disorders. In non-dividing cells such as neuronal tissue and platelets septins have been associated with exocytosis. However, many mechanistic details and roles attributed to septins are poorly understood. We describe here some important mammalian septin interactions with a special focus on the clinically relevant septin interactions. PMID:28224124

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

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    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. Analysis of septins across kingdoms reveals orthology and new motifs

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    Malmberg Russell L

    2007-07-01

    Full Text Available Abstract Background Septins are cytoskeletal GTPase proteins first discovered in the fungus Saccharomyces cerevisiae where they organize the septum and link nuclear division with cell division. More recently septins have been found in animals where they are important in processes ranging from actin and microtubule organization to embryonic patterning and where defects in septins have been implicated in human disease. Previous studies suggested that many animal septins fell into independent evolutionary groups, confounding cross-kingdom comparison. Results In the current work, we identified 162 septins from fungi, microsporidia and animals and analyzed their phylogenetic relationships. There was support for five groups of septins with orthology between kingdoms. Group 1 (which includes S. cerevisiae Cdc10p and human Sept9 and Group 2 (which includes S. cerevisiae Cdc3p and human Sept7 contain sequences from fungi and animals. Group 3 (which includes S. cerevisiae Cdc11p and Group 4 (which includes S. cerevisiae Cdc12p contain sequences from fungi and microsporidia. Group 5 (which includes Aspergillus nidulans AspE contains sequences from filamentous fungi. We suggest a modified nomenclature based on these phylogenetic relationships. Comparative sequence alignments revealed septin derivatives of already known G1, G3 and G4 GTPase motifs, four new motifs from two to twelve amino acids long and six conserved single amino acid positions. One of these new motifs is septin-specific and several are group specific. Conclusion Our studies provide an evolutionary history for this important family of proteins and a framework and consistent nomenclature for comparison of septin orthologs across kingdoms.

  9. Septin phosphorylation and coiled-coil domains function in cell and septin ring morphology in the filamentous fungus Ashbya gossypii.

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    Meseroll, Rebecca A; Occhipinti, Patricia; Gladfelter, Amy S

    2013-02-01

    Septins are a class of GTP-binding proteins conserved throughout many eukaryotes. Individual septin subunits associate with one another and assemble into heteromeric complexes that form filaments and higher-order structures in vivo. The mechanisms underlying the assembly and maintenance of higher-order structures in cells remain poorly understood. Septins in several organisms have been shown to be phosphorylated, although precisely how septin phosphorylation may be contributing to the formation of high-order septin structures is unknown. Four of the five septins expressed in the filamentous fungus, Ashbya gossypii, are phosphorylated, and we demonstrate here the diverse roles of these phosphorylation sites in septin ring formation and septin dynamics, as well as cell morphology and viability. Intriguingly, the alteration of specific sites in Cdc3p and Cdc11p leads to a complete loss of higher-order septin structures, implicating septin phosphorylation as a regulator of septin structure formation. Introducing phosphomimetic point mutations to specific sites in Cdc12p and Shs1p causes cell lethality, highlighting the importance of normal septin modification in overall cell function and health. In addition to discovering roles for phosphorylation, we also present diverse functions for conserved septin domains in the formation of septin higher-order structure. We previously showed the requirement for the Shs1p coiled-coil domain in limiting septin ring size and reveal here that, in contrast to Shs1p, the coiled-coil domains of Cdc11p and Cdc12p are required for septin ring formation. Our results as a whole reveal novel roles for septin phosphorylation and coiled-coil domains in regulating septin structure and function.

  10. Septin functions in organ system physiology and pathology

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    2014-01-01

    Human septins comprise a family of 13 genes that encode for >30 protein isoforms with ubiquitous and tissue-specific expressions. Septins are GTP-binding proteins that assemble into higher-order oligomers and filamentous polymers, which associate with cell membranes and the cytoskeleton. In the last decade, much progress has been made in understanding the biochemical properties and cell biological functions of septins. In parallel, a growing number of studies show that septins play important ...

  11. Septin functions in organ system physiology and pathology

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    Dolat, Lee; Hu, Qicong

    2015-01-01

    Human septins comprise a family of 13 genes that encode for >30 protein isoforms with ubiquitous and tissue-specific expressions. Septins are GTP-binding proteins that assemble into higher-order oligomers and filamentous polymers, which associate with cell membranes and the cytoskeleton. In the last decade, much progress has been made in understanding the biochemical properties and cell biological functions of septins. In parallel, a growing number of studies show that septins play important roles for the development and physiology of specific tissues and organs. Here, we review the expression and function of septins in the cardiovascular, immune, nervous, urinary, digestive, respiratory, endocrine, reproductive, and integumentary organ systems. Furthermore, we discuss how the tissue-specific functions of septins relate to the pathology of human diseases that arise from aberrations in septin expression. PMID:24114910

  12. Cytoskeleton: cirque du septins.

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    Gladfelter, Amy S

    2014-06-02

    Septins and F-actin are familiar cohabitants of the cleavage furrow yet how they might be functionally connected has been ambiguous. New work shows that septins can promote the assembly of curved bundles of F-actin, providing an unexpected molecular function for septins in cytokinesis.

  13. Septins as modulators of endo-lysosomal membrane traffic

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    Kyungyeun Song

    2016-11-01

    Full Text Available Septins constitute a family of GTP-binding proteins, which assemble into non-polar filaments in a nucleotide-dependent manner. These filaments can be recruited to negatively charged membrane surfaces. When associated with membranes septin filaments can act as diffusion barriers, which confine subdomains of distinct biological functions. In addition, they serve scaffolding roles by recruiting cytosolic proteins and other cytoskeletal elements. Septins have been implicated in a large variety of membrane-dependent processes, including cytokinesis, signaling, cell migration, and membrane traffic, and several family members have been implicated in disease. However, surprisingly little is known about the molecular mechanisms underlying their biological functions. This review summarizes evidence in support of regulatory roles of septins during endo-lysosomal sorting, with a particular focus on phosphoinositides, which serve as spatial landmarks guiding septin recruitment to distinct subcellular localizations.

  14. Septins of Platyhelminths: Identification, Phylogeny, Expression and Localization among Developmental Stages of Schistosoma mansoni

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    Zeraik, Ana E.; Rinaldi, Gabriel; Mann, Victoria H.; Popratiloff, Anastas; Araujo, Ana P. U.; DeMarco, Ricardo; Brindley, Paul J.

    2013-01-01

    Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle of the schistosome and a similar expression profile was observed for septins in the stages examined, consistent with concerted production of these proteins to form heterocomplexes. Immunolocalization analyses undertaken with antibodies specific for SmSEPT5 and SmSEPT10 revealed a broad tissue distribution of septins in the schistosomulum and colocalization of septin and actin in the longitudinal and circular muscles of the sporocyst. Ciliated epidermal plates of the miracidium were rich in septins. Expression levels for these septins were elevated in germ cells in the miracidium and sporocyst. Intriguingly, septins colocalize with the protonephridial system of the cercaria, which extends laterally along the length of this larval stage. Together, the findings revealed that schistosomes expressed several septins which likely form filaments within the cells, as in other eukaryotes. Identification and localization demonstrating a broad distribution of septins across organs and tissues of schistosome contributes towards the understanding of septins in schistosomes and other flatworms. PMID:24367716

  15. Septins of Platyhelminths: identification, phylogeny, expression and localization among developmental stages of Schistosoma mansoni.

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    Zeraik, Ana E; Rinaldi, Gabriel; Mann, Victoria H; Popratiloff, Anastas; Araujo, Ana P U; Demarco, Ricardo; Brindley, Paul J

    2013-01-01

    Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle of the schistosome and a similar expression profile was observed for septins in the stages examined, consistent with concerted production of these proteins to form heterocomplexes. Immunolocalization analyses undertaken with antibodies specific for SmSEPT5 and SmSEPT10 revealed a broad tissue distribution of septins in the schistosomulum and colocalization of septin and actin in the longitudinal and circular muscles of the sporocyst. Ciliated epidermal plates of the miracidium were rich in septins. Expression levels for these septins were elevated in germ cells in the miracidium and sporocyst. Intriguingly, septins colocalize with the protonephridial system of the cercaria, which extends laterally along the length of this larval stage. Together, the findings revealed that schistosomes expressed several septins which likely form filaments within the cells, as in other eukaryotes. Identification and localization demonstrating a broad distribution of septins across organs and tissues of schistosome contributes towards the understanding of septins in schistosomes and other flatworms.

  16. Septins of Platyhelminths: identification, phylogeny, expression and localization among developmental stages of Schistosoma mansoni.

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    Ana E Zeraik

    Full Text Available Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle of the schistosome and a similar expression profile was observed for septins in the stages examined, consistent with concerted production of these proteins to form heterocomplexes. Immunolocalization analyses undertaken with antibodies specific for SmSEPT5 and SmSEPT10 revealed a broad tissue distribution of septins in the schistosomulum and colocalization of septin and actin in the longitudinal and circular muscles of the sporocyst. Ciliated epidermal plates of the miracidium were rich in septins. Expression levels for these septins were elevated in germ cells in the miracidium and sporocyst. Intriguingly, septins colocalize with the protonephridial system of the cercaria, which extends laterally along the length of this larval stage. Together, the findings revealed that schistosomes expressed several septins which likely form filaments within the cells, as in other eukaryotes. Identification and localization demonstrating a broad distribution of septins across organs and tissues of schistosome contributes towards the understanding of septins in schistosomes and other flatworms.

  17. Septin pairs, a complex choreography.

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    Ewers, Helge

    2011-06-13

    Septins form a filamentous collar at the mother-bud neck in budding yeast. In cytokinesis, this collar splits into two rings and the septin complexes undergo a dramatic reorientation. Using fluorescence polarization microscopy, DeMay et al. (2011. J. Cell Biol. doi:10.1083/jcb.201012143) now demonstrate that septin complexes assemble as paired filaments in vivo and reveal new insights into septin organization during cytokinesis.

  18. Potential role of septins in oral carcinogenesis: An update and avenues for future research

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    Rooban Thavarajah

    2012-01-01

    Full Text Available Septins belong to the GTPase superclass of conserved proteins and have been identified to play a role in diverse aspects of cell biology, from cytokinesis to the maintenance of cellular morphology. At least 14 septins have been identified in humans. With their complex patterns in gene expressions and interaction, it has been reported that alterations in septin expression are observed in human diseases. Although much is not known about the role of human septins in oral carcinogenesis, circumstantial evidence does indicate that it may play a major role. This review intends to summarize the basis of septin biology, with the focus being on the evidence for septin involvement in human oral cancer.

  19. Septins promote F-actin ring formation by crosslinking actin filaments into curved bundles.

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    Mavrakis, Manos; Azou-Gros, Yannick; Tsai, Feng-Ching; Alvarado, José; Bertin, Aurélie; Iv, Francois; Kress, Alla; Brasselet, Sophie; Koenderink, Gijsje H; Lecuit, Thomas

    2014-04-01

    Animal cell cytokinesis requires a contractile ring of crosslinked actin filaments and myosin motors. How contractile rings form and are stabilized in dividing cells remains unclear. We address this problem by focusing on septins, highly conserved proteins in eukaryotes whose precise contribution to cytokinesis remains elusive. We use the cleavage of the Drosophila melanogaster embryo as a model system, where contractile actin rings drive constriction of invaginating membranes to produce an epithelium in a manner akin to cell division. In vivo functional studies show that septins are required for generating curved and tightly packed actin filament networks. In vitro reconstitution assays show that septins alone bundle actin filaments into rings, accounting for the defects in actin ring formation in septin mutants. The bundling and bending activities are conserved for human septins, and highlight unique functions of septins in the organization of contractile actomyosin rings.

  20. Mammalian SEPT9 isoforms direct microtubule-dependent arrangements of septin core heteromers.

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    Sellin, Mikael E; Stenmark, Sonja; Gullberg, Martin

    2012-11-01

    Septin-family proteins assemble into rod-shaped heteromeric complexes that form higher-order arrangements at the cell cortex, where they serve apparently conserved functions as diffusion barriers and molecular scaffolds. There are 13 confirmed septin paralogues in mammals, which may be ubiquitous or tissue specific. Septin hetero-oligomerization appears homology subgroup directed, which in turn determines the subunit arrangement of six- to eight-subunit core heteromers. Here we address functional properties of human SEPT9, which, due to variable mRNA splicing, exists as multiple isoforms that differ between tissues. Myeloid K562 cells express three SEPT9 isoforms, all of which have an equal propensity to hetero-oligomerize with SEPT7-containing hexamers to generate octameric heteromers. However, due to limiting amounts of SEPT9, K562 cells contain both hexameric and octameric heteromers. To generate cell lines with controllable hexamer-to-octamer ratios and that express single SEPT9 isoforms, we developed a gene product replacement strategy. By this means we identified SEPT9 isoform-specific properties that either facilitate septin heteromer polymerization along microtubules or modulate the size range of submembranous septin disks-a prevalent septin structure in nonadhered cells. Our findings show that the SEPT9 expression level directs the hexamer-to-octamer ratio, and that the isoform composition and expression level together determine higher-order arrangements of septins.

  1. Septin9 is involved in septin filament formation and cellular stability

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    Füchtbauer, Annette C.; Lassen, Louise Berkhoudt; Jensen, Astrid Bøgh

    2011-01-01

    Septin9 (Sept9) is a member of the filament-forming septin family of structural proteins and is associated with a variety of cancers and with hereditary neuralgic amyotrophy. We have generated mice with constitutive and conditional Sept9 knockout alleles. Homozygous deletion of Sept9 results in e...

  2. Septin localization across kingdoms: three themes with variations.

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    Lindsey, Rebecca; Momany, Michelle

    2006-12-01

    Septins are GTPases that form filaments in fungi and animals. In addition to their original role in cell division, septins have been shown to have roles in coordinating nuclear division, membrane trafficking and organizing the cytoskeleton. Many recent studies have examined subcellular localization of septins in a wide range of fungi and animals. Septin localization shows three patterns, which generally correspond to function across kingdoms. Septins that localize to projections shape and compartmentalize emerging growth. Septins that localize to partitions compartmentalize pre-existing cellular material. Septins that localize to the whole cell are involved in membrane trafficking and organizing the cytoskeleton and are most often in animals. The difference in localization pattern frequency between kingdoms will probably disappear as more septins are examined in diverse organisms and tissues.

  3. Septin Phosphorylation and Coiled-Coil Domains Function in Cell and Septin Ring Morphology in the Filamentous Fungus Ashbya gossypii

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    Meseroll, Rebecca A.; Occhipinti, Patricia; Gladfelter, Amy S.

    2013-01-01

    Septins are a class of GTP-binding proteins conserved throughout many eukaryotes. Individual septin subunits associate with one another and assemble into heteromeric complexes that form filaments and higher-order structures in vivo. The mechanisms underlying the assembly and maintenance of higher-order structures in cells remain poorly understood. Septins in several organisms have been shown to be phosphorylated, although precisely how septin phosphorylation may be contributing to the formati...

  4. Characterization of Septin Ultrastructure in Budding Yeast Using Electron Tomography

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    Bertin, Aurélie; Nogales, Eva

    2015-01-01

    Summary Septins are essential for the completion of cytokinesis. In budding yeast, Saccharomyces cerevisiae, septins are located at the bud neck during mitosis and are closely connected to the inner plasma membrane. In vitro, yeast septins have been shown to self-assemble into a variety of filamentous structures, including rods, paired filaments, bundles and rings [1–3]. Using electron tomography of freeze-substituted section and cryo-electron tomography of frozen sections, we determined the three dimensional organization of the septin cytoskeleton in dividing budding yeast with molecular resolution [4,5]. Here we describe the detailed procedures used for our characterization of the septin cellular ultrastructure. PMID:26519309

  5. Deciphering the rules governing assembly order of mammalian septin complexes.

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    Sellin, Mikael E; Sandblad, Linda; Stenmark, Sonja; Gullberg, Martin

    2011-09-01

    Septins are conserved GTP-binding proteins that assemble into lateral diffusion barriers and molecular scaffolds. Vertebrate genomes contain 9-17 septin genes that encode both ubiquitous and tissue-specific septins. Expressed septins may assemble in various combinations through both heterotypic and homotypic G-domain interactions. However, little is known regarding assembly states of mammalian septins and mechanisms directing ordered assembly of individual septins into heteromeric units, which is the focus of this study. Our analysis of the septin system in cells lacking or overexpressing selected septins reveals interdependencies coinciding with previously described homology subgroups. Hydrodynamic and single-particle data show that individual septins exist solely in the context of stable six- to eight-subunit core heteromers, all of which contain SEPT2 and SEPT6 subgroup members and SEPT7, while heteromers comprising more than six subunits also contain SEPT9. The combined data suggest a generic model for how the temporal order of septin assembly is homology subgroup-directed, which in turn determines the subunit arrangement of native heteromers. Because mammalian cells normally express multiple members and/or isoforms of some septin subgroups, our data also suggest that only a minor fraction of native heteromers are arranged as perfect palindromes.

  6. Septins localize to microtubules during nutritional limitation in Saccharomyces cerevisiae

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    Vázquez de Aldana Carlos R

    2008-10-01

    Full Text Available Abstract Background In Saccharomyces cerevisiae, nutrient limitation stimulates diploid cells to undergo DNA replication and meiosis, followed by the formation of four haploid spores. Septins are a family of proteins that assemble a ring structure at the mother-daughter neck during vegetative growth, where they control cytokinesis. In sporulating cells, the septin ring disassembles and septins relocalize to the prospore membrane. Results Here, we demonstrate that nutrient limitation triggers a change in the localization of at least two vegetative septins (Cdc10 and Cdc11 from the bud neck to the microtubules. The association of Cdc10 and Cdc11 with microtubules persists into meiosis, and they are found associated with the meiotic spindle until the end of meiosis II. In addition, the meiosis-specific septin Spr28 displays similar behavior, suggesting that this is a common feature of septins. Septin association to microtubules is a consequence of the nutrient limitation signal, since it is also observed when haploid cells are incubated in sporulation medium and when haploid or diploid cells are grown in medium containing non-fermentable carbon sources. Moreover, during meiosis II, when the nascent prospore membrane is formed, septins moved from the microtubules to this membrane. Proper organization of the septins on the membrane requires the sporulation-specific septins Spr3 and Spr28. Conclusion Nutrient limitation in S. cerevisiae triggers the sporulation process, but it also induces the disassembly of the septin bud neck ring and relocalization of the septin subunits to the nucleus. Septins remain associated with microtubules during the meiotic divisions and later, during spore morphogenesis, they are detected associated to the nascent prospore membranes surrounding each nuclear lobe. Septin association to microtubules also occurs during growth in non-fermentable carbon sources.

  7. Investigation of septins using infection by bacterial pathogens.

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    Krokowski, S; Mostowy, S

    2016-01-01

    Investigation of the host cytoskeleton during infection by bacterial pathogens has significantly contributed to our understanding of cell biology and host defense. Work has shown that septins are recruited to the phagocytic cup as collarlike structures and enable bacterial entry into host cells. In the cytosol, septins can entrap actin-polymerizing bacteria in cage-like structures for targeting to autophagy, a highly conserved intracellular degradation process. In this chapter, we describe methods to investigate septin assembly and function during infection by bacterial pathogens. Use of these methods can lead to in-depth understanding of septin biology and suggest therapeutic approaches to combat infectious disease.

  8. Mitochondria mediate septin cage assembly to promote autophagy of Shigella.

    Science.gov (United States)

    Sirianni, Andrea; Krokowski, Sina; Lobato-Márquez, Damián; Buranyi, Stephen; Pfanzelter, Julia; Galea, Dieter; Willis, Alexandra; Culley, Siân; Henriques, Ricardo; Larrouy-Maumus, Gerald; Hollinshead, Michael; Sancho-Shimizu, Vanessa; Way, Michael; Mostowy, Serge

    2016-07-01

    Septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic Shigella flexneri and promote their targeting to autophagosomes. However, the processes underlying septin cage assembly, and whether they influence S. flexneri proliferation, remain to be established. Using single-cell analysis, we show that the septin cages inhibit S. flexneri proliferation. To study mechanisms of septin cage assembly, we used proteomics and found mitochondrial proteins associate with septins in S. flexneri-infected cells. Strikingly, mitochondria associated with S. flexneri promote septin assembly into cages that entrap bacteria for autophagy. We demonstrate that the cytosolic GTPase dynamin-related protein 1 (Drp1) interacts with septins to enhance mitochondrial fission. To avoid autophagy, actin-polymerising Shigella fragment mitochondria to escape from septin caging. Our results demonstrate a role for mitochondria in anti-Shigella autophagy and uncover a fundamental link between septin assembly and mitochondria. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  9. Analysis of Septin Reorganization at Cytokinesis Using Polarized Fluorescence Microscopy

    Directory of Open Access Journals (Sweden)

    Molly McQuilken

    2017-05-01

    Full Text Available Septins are conserved filament-forming proteins that act in diverse cellular processes. They closely associate with membranes and, in some systems, components of the cytoskeleton. It is not well understood how filaments assemble into higher-order structures in vivo or how they are remodeled throughout the cell cycle. In the budding yeast S. cerevisiae, septins are found through most of the cell cycle in an hourglass organization at the mother-bud neck until cytokinesis when the collar splits into two rings that disassemble prior to the next cell cycle. Experiments using polarized fluorescence microscopy have suggested that septins are arranged in ordered, paired filaments in the hourglass and undergo a coordinated 90° reorientation during splitting at cytokinesis. This apparent reorganization could be due to two orthogonal populations of filaments disassembling and reassembling or being preferentially retained at cytokinesis. In support of this idea, we report a decrease in septin concentration at the mother-bud neck during cytokinesis consistent with other reports and the timing of the decrease depends on known septin regulators including the Gin4 kinase. We took a candidate-based approach to examine what factors control reorientation during splitting and used polarized fluorescence microscopy to screen mutant yeast strains deficient in septin interacting proteins. Using this method, we have linked known septin regulators to different aspects of the assembly, stability, and reorganization of septin assemblies. The data support that ring splitting requires Gin4 activity and an anillin-like protein Bud4, and normal accumulation of septins at the ring requires phosphorylation of Shs1. We found distinct regulatory requirements for septin organization in the hourglass compared to split rings. We propose that septin subpopulations can vary in their localization and assembly/disassembly behavior in a cell-cycle dependent manner at cytokinesis.

  10. Septin9 is involved in septin filament formation and cellular stability.

    Science.gov (United States)

    Füchtbauer, Annette; Lassen, Louise B; Jensen, Astrid B; Howard, Jennifer; Quiroga, Adán de Salas; Warming, Søren; Sørensen, Annette B; Pedersen, Finn S; Füchtbauer, Ernst-Martin

    2011-08-01

    Septin9 (Sept9) is a member of the filament-forming septin family of structural proteins and is associated with a variety of cancers and with hereditary neuralgic amyotrophy. We have generated mice with constitutive and conditional Sept9 knockout alleles. Homozygous deletion of Sept9 results in embryonic lethality around day 10 of gestation whereas mice homozygous for the conditional allele develop normally. Here we report the consequences of homozygous loss of Sept9 in immortalized murine embryonic fibroblasts. Proliferation rate was not changed but cells without Sept9 had an altered morphology compared to normal cells, particularly under low serum stress. Abnormal, fragmented, and multiple nuclei were more frequent in cells without Sept9. Cell migration, as measured by gap-filling and filter-invasion assays, was impaired, but individual cells did not move less than wild-type cells. Sept9 knockout cells showed a reduced resistance to hypo-osmotic stress. Stress fiber and vinculin staining at focal adhesion points was less prominent. Long septin filaments stained for Sept7 disappeared. Instead, staining was found in short, often curved filaments and rings. Furthermore, Sept7 was no longer localized to the mitotic spindle. Together, these data reveal the importance of Sept9 for septin filament formation and general cell stability.

  11. Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus.

    Science.gov (United States)

    Vargas-Muñiz, José M; Renshaw, Hilary; Waitt, Greg; Soderblom, Erik J; Moseley, M Arthur; Palmer, Jonathan M; Juvvadi, Praveen R; Keller, Nancy P; Steinbach, William J

    2017-04-01

    Aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. Septins, a conserved family of GTP-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators to different cellular compartments. Deletion of the A. fumigatus septin aspB increases susceptibility to the echinocandin antifungal caspofungin. However, how AspB mediates this response to caspofungin is unknown. Here, we characterized the AspB interactome under basal conditions and after exposure to a clinically relevant concentration of caspofungin. While A. fumigatus AspB interacted with 334 proteins, including kinases, cell cycle regulators, and cell wall synthesis-related proteins under basal growth conditions, caspofungin exposure altered AspB interactions. A total of 69 of the basal interactants did not interact with AspB after exposure to caspofungin, and 54 new interactants were identified following caspofungin exposure. We generated A. fumigatus deletion strains for 3 proteins (ArpB, Cyp4, and PpoA) that only interacted with AspB following exposure to caspofungin that were previously annotated as induced after exposure to antifungal agents, yet only PpoA was implicated in the response to caspofungin. Taken together, we defined how the septin AspB interactome is altered in the presence of a clinically relevant antifungal.

  12. Septin 9 interacts with kinesin KIF17 and interferes with the mechanism of NMDA receptor cargo binding and transport.

    Science.gov (United States)

    Bai, Xiaobo; Karasmanis, Eva P; Spiliotis, Elias T

    2016-03-15

    Intracellular transport involves the regulation of microtubule motor interactions with cargo, but the underlying mechanisms are not well understood. Septins are membrane- and microtubule-binding proteins that assemble into filamentous, scaffold-like structures. Septins are implicated in microtubule-dependent transport, but their roles are unknown. Here we describe a novel interaction between KIF17, a kinesin 2 family motor, and septin 9 (SEPT9). We show that SEPT9 associates directly with the C-terminal tail of KIF17 and interacts preferentially with the extended cargo-binding conformation of KIF17. In developing rat hippocampal neurons, SEPT9 partially colocalizes and comigrates with KIF17. We show that SEPT9 interacts with the KIF17 tail domain that associates with mLin-10/Mint1, a cargo adaptor/scaffold protein, which underlies the mechanism of KIF17 binding to the NMDA receptor subunit 2B (NR2B). Significantly, SEPT9 interferes with binding of the PDZ1 domain of mLin-10/Mint1 to KIF17 and thereby down-regulates NR2B transport into the dendrites of hippocampal neurons. Measurements of KIF17 motility in live neurons show that SEPT9 does not affect the microtubule-dependent motility of KIF17. These results provide the first evidence of an interaction between septins and a nonmitotic kinesin and suggest that SEPT9 modulates the interactions of KIF17 with membrane cargo.

  13. Septins and Generation of Asymmetries in Fungal Cells

    Science.gov (United States)

    Khan, Anum; McQuilken, Molly

    2017-01-01

    Polarized growth is critical for the development and maintenance of diverse organisms and tissues, but particularly central to fungi where nutrient uptake, communication, and reproduction all rely on cell asymmetries. To achieve polarized growth, fungi spatially organize both their cytosol and cortical membranes. The septins, a family of GTP-binding proteins, have emerged as key regulators of spatial compartmentalization in fungi and other eukaryotes. By forming higher-order structures on fungal plasma membranes, septins are thought to contribute to the generation of cell asymmetries by acting as molecular scaffolds and forming diffusional barriers. Here we discuss the links between septins and polarized growth and consider molecular models for how septins contribute to cellular asymmetry in fungi. PMID:26488282

  14. Septins and Generation of Asymmetries in Fungal Cells.

    Science.gov (United States)

    Khan, Anum; McQuilken, Molly; Gladfelter, Amy S

    2015-01-01

    Polarized growth is critical for the development and maintenance of diverse organisms and tissues but particularly so in fungi, where nutrient uptake, communication, and reproduction all rely on cell asymmetries. To achieve polarized growth, fungi spatially organize both their cytosol and cortical membranes. Septins, a family of GTP-binding proteins, are key regulators of spatial compartmentalization in fungi and other eukaryotes. Septins form higher-order structures on fungal plasma membranes and are thought to contribute to the generation of cell asymmetries by acting as molecular scaffolds and forming diffusional barriers. Here we discuss the links between septins and polarized growth and consider molecular models for how septins contribute to cellular asymmetry in fungi.

  15. Septins from the phytopathogenic fungus Ustilago maydis are required for proper morphogenesis but dispensable for virulence.

    Directory of Open Access Journals (Sweden)

    Isabel Alvarez-Tabarés

    Full Text Available BACKGROUND: Septins are a highly conserved family of GTP-binding proteins involved in multiple cellular functions, including cell division and morphogenesis. Studies of septins in fungal cells underpin a clear correlation between septin-based structures and fungal morphology, providing clues to understand the molecular frame behind the varied morphologies found in fungal world. METHODOLOGY/PRINCIPAL FINDINGS: Ustilago maydis genome has the ability to encode four septins. Here, using loss-of-function as well as GFP-tagged alleles of these septin genes, we investigated the roles of septins in the morphogenesis of this basidiomycete fungus. We described that septins in U. maydis could assemble into at least three different structures coexisting in the same cell: bud neck collars, band-like structures at the growing tip, and long septin fibers that run from pole to pole near the cell cortex. We also found that in the absence of septins, U. maydis cells lost their elongated shape, became wider at the central region and ended up losing their polarity, pointing to an important role of septins in the morphogenesis of this fungus. These morphological defects were alleviated in the presence of an osmotic stabilizer suggesting that absence of septins affected the proper formation of the cell wall, which was coherent with a higher sensitivity of septin defective cells to drugs that affect cell wall construction as well as exocytosis. As U. maydis is a phytopathogen, we analyzed the role of septins in virulence and found that in spite of the described morphological defects, septin mutants were virulent in corn plants. CONCLUSIONS/SIGNIFICANCE: Our results indicated a major role of septins in morphogenesis in U. maydis. However, in contrast to studies in other fungal pathogens, in which septins were reported to be necessary during the infection process, we found a minor role of septins during corn infection by U. maydis.

  16. Septin 7 forms a complex with CD2AP and nephrin and regulates glucose transporter trafficking.

    Science.gov (United States)

    Wasik, Anita A; Polianskyte-Prause, Zydrune; Dong, Meng-Qiu; Shaw, Andrey S; Yates, John R; Farquhar, Marilyn G; Lehtonen, Sanna

    2012-09-01

    Podocytes are insulin-sensitive and take up glucose in response to insulin. This requires nephrin, which interacts with vesicle-associated membrane protein 2 (VAMP2) on GLUT4 storage vesicles (GSVs) and facilitates their fusion with the plasma membrane. In this paper, we show that the filament-forming GTPase septin 7 is expressed in podocytes and associates with CD2-associated protein (CD2AP) and nephrin, both essential for glomerular ultrafiltration. In addition, septin 7 coimmunoprecipitates with VAMP2. Subcellular fractionation of cultured podocytes revealed that septin 7 is found in both cytoplasmic and membrane fractions, and immunofluorescence microscopy showed that septin 7 is expressed in a filamentous pattern and is also found on vesicles and the plasma membrane. The filamentous localization of septin 7 depends on CD2AP and intact actin organization. A 2-deoxy-d-glucose uptake assay indicates that depletion of septin 7 by small interfering RNA or alteration of septin assembly by forchlorfenuron facilitates glucose uptake into cells and further, knockdown of septin 7 increased the interaction of VAMP2 with nephrin and syntaxin 4. The data indicate that septin 7 hinders GSV trafficking and further, the interaction of septin 7 with nephrin in glomeruli suggests that septin 7 may participate in the regulation of glucose transport in podocytes.

  17. Septin 9 hypermethylation contributes to migration and resistance to ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2017; 16 (4): 803-810 ... Keywords: Septin 9, Hypermethylation, Colorectal cancer, Drug resistance, Rho A signaling ... 100 with 0 being no methylation and 100 ... the top side, the cells that are migrated to the ..... Yang SY, Sales KM, Fuller B, Seifalian AM, Winslet MC.

  18. In silico docking of forchlorfenuron (FCF to septins suggests that FCF interferes with GTP binding.

    Directory of Open Access Journals (Sweden)

    Dimitrios Angelis

    Full Text Available Septins are GTP-binding proteins that form cytoskeleton-like filaments, which are essential for many functions in eukaryotic organisms. Small molecule compounds that disrupt septin filament assembly are valuable tools for dissecting septin functions with high temporal control. To date, forchlorfenuron (FCF is the only compound known to affect septin assembly and functions. FCF dampens the dynamics of septin assembly inducing the formation of enlarged stable polymers, but the underlying mechanism of action is unknown. To investigate how FCF binds and affects septins, we performed in silico simulations of FCF docking to all available crystal structures of septins. Docking of FCF with SEPT2 and SEPT3 indicated that FCF interacts preferentially with the nucleotide-binding pockets of septins. Strikingly, FCF is predicted to form hydrogen bonds with residues involved in GDP-binding, mimicking nucleotide binding. FCF docking with the structure of SEPT2-GppNHp, a nonhydrolyzable GTP analog, and SEPT7 showed that FCF may assume two alternative non-overlapping conformations deeply into and on the outer side of the nucleotide-binding pocket. Surprisingly, FCF was predicted to interact with the P-loop Walker A motif GxxxxGKS/T, which binds the phosphates of GTP, and the GTP specificity motif AKAD, which interacts with the guanine base of GTP, and highly conserved amino acids including a threonine, which is critical for GTP hydrolysis. Thus, in silico FCF exhibits a conserved mechanism of binding, interacting with septin signature motifs and residues involved in GTP binding and hydrolysis. Taken together, our results suggest that FCF stabilizes septins by locking them into a conformation that mimics a nucleotide-bound state, preventing further GTP binding and hydrolysis. Overall, this study provides the first insight into how FCF may bind and stabilize septins, and offers a blueprint for the rational design of FCF derivatives that could target septins with

  19. Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility.

    Science.gov (United States)

    Tooley, Aaron J; Gilden, Julia; Jacobelli, Jordan; Beemiller, Peter; Trimble, William S; Kinoshita, Makoto; Krummel, Matthew F

    2009-01-01

    The systems that refine actomyosin forces during motility remain poorly understood. Septins assemble on the T-cell cortex and are enriched at the mid-zone in filaments. Septin knockdown causes membrane blebbing, excess leading-edge protrusions and lengthening of the trailing-edge uropod. The associated loss of rigidity permits motility, but cells become uncoordinated and poorly persistent. This also relieves a previously unrecognized restriction to migration through small pores. Pharmacologically rigidifying cells counteracts this effect, and relieving cytoskeletal rigidity synergizes with septin depletion. These data suggest that septins tune actomyosin forces during motility and probably regulate lymphocyte trafficking in confined tissues.

  20. Recruitment of septin cytoskeletal proteins by botulinum toxin A protease determines its remarkable stability.

    Science.gov (United States)

    Vagin, Olga; Tokhtaeva, Elmira; Garay, Patton E; Souda, Puneet; Bassilian, Sara; Whitelegge, Julian P; Lewis, Ramilla; Sachs, George; Wheeler, Larry; Aoki, Roger; Fernandez-Salas, Ester

    2014-08-01

    Proteolytic cleavage of synaptosomal-associated protein 25 by the light chain of botulinum neurotoxin type A (LCA) results in a blockade of neurotransmitter release that persists for several months in motor neurons. The L428A/L429A mutation in LCA is known to significantly shorten both the proteolytic and neuroparalytic effects of the neurotoxin in mice. To elucidate the cellular mechanism for LCA longevity, we studied the effects of L428A/L429A mutation on the interactome, localization and stability of LCA expressed in cultured neuronal cells. Mass spectrometry analysis of the LCA interactome showed that the mutation prevented the interaction of LCA with septins. The wild-type LCA was concentrated in plasma-membrane-associated clusters, colocalizing with septins-2 and septin-7, which accumulated in these clusters only in the presence of LCA. The L428A/L429A mutation decreased co-clustering of LCA and septins and accelerated proteasomal and non-proteasomal degradation of LCA. Similarly, the impairment of septin oligomerization by forchlorfenuron or silencing of septin-2 prevented LCA interaction and clustering with septins and increased LCA degradation. Therefore, the dileucine-mediated LCA-septin co-clustering is crucial for the long-lasting stabilization of LCA-related proteolytic and presumably neuroparalytic activity. © 2014. Published by The Company of Biologists Ltd.

  1. Identification of Cell Cycle Dependent Interaction Partners of the Septins by Quantitative Mass Spectrometry.

    Directory of Open Access Journals (Sweden)

    Christian Renz

    Full Text Available The septins are a conserved family of GTP-binding proteins that, in the baker's yeast, assemble into a highly ordered array of filaments at the mother bud neck. These filaments undergo significant structural rearrangements during the cell cycle. We aimed at identifying key components that are involved in or regulate the transitions of the septins. By combining cell synchronization and quantitative affinity-purification mass-spectrometry, we performed a screen for specific interaction partners of the septins at three distinct stages of the cell cycle. A total of 83 interaction partners of the septins were assigned. Surprisingly, we detected DNA-interacting/nuclear proteins and proteins involved in ribosome biogenesis and protein synthesis predominantly present in alpha-factor arrested that do not display an assembled septin structure. Furthermore, two distinct sets of regulatory proteins that are specific for cells at S-phase with a stable septin collar or at mitosis with split septin rings were identified. Complementary methods like SPLIFF and immunoprecipitation allowed us to more exactly define the spatial and temporal characteristics of selected hits of the AP-MS screen.

  2. Septins and the lateral compartmentalization of eukaryotic membranes.

    Science.gov (United States)

    Caudron, Fabrice; Barral, Yves

    2009-04-01

    Eukaryotic cells from neurons and epithelial cells to unicellular fungi frequently rely on cellular appendages such as axons, dendritic spines, cilia, and buds for their biology. The emergence and differentiation of these appendages depend on the formation of lateral diffusion barriers at their bases to insulate their membranes from the rest of the cell. Here, we review recent progress regarding the molecular mechanisms and functions of such barriers. This overview underlines the importance and conservation of septin-dependent diffusion barriers, which coordinately compartmentalize both plasmatic and internal membranes. We discuss their role in memory establishment and the control of cellular aging.

  3. Some Implications of Human-Structure Interaction

    DEFF Research Database (Denmark)

    Pedersen, Lars

    2013-01-01

    On structures, humans may be active which may cause structural vibrations as human activity can excite structural vibration modes. However, humans may also be passive (sitting or standing on the structure). The paper addresses this subject and explores the implications of having passive humans pr...

  4. Molecular Memory of Morphologies by Septins during Neuron Generation Allows Early Polarity Inheritance.

    Science.gov (United States)

    Boubakar, Leila; Falk, Julien; Ducuing, Hugo; Thoinet, Karine; Reynaud, Florie; Derrington, Edmund; Castellani, Valérie

    2017-08-16

    Transmission of polarity established early during cell lineage history is emerging as a key process guiding cell differentiation. Highly polarized neurons provide a fascinating model to study inheritance of polarity over cell generations and across morphological transitions. Neural crest cells (NCCs) migrate to the dorsal root ganglia to generate neurons directly or after cell divisions in situ. Using live imaging of vertebrate embryo slices, we found that bipolar NCC progenitors lose their polarity, retracting their processes to round for division, but generate neurons with bipolar morphology by emitting processes from the same locations as the progenitor. Monitoring the dynamics of Septins, which play key roles in yeast polarity, indicates that Septin 7 tags process sites for re-initiation of process growth following mitosis. Interfering with Septins blocks this mechanism. Thus, Septins store polarity features during mitotic rounding so that daughters can reconstitute the initial progenitor polarity. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Septin 7 forms a complex with CD2AP and nephrin and regulates glucose transporter trafficking

    OpenAIRE

    Wasik, A. A.; Polianskyte-Prause, Z.; Dong, M.-Q.; Shaw, A S; Yates, J R; Farquhar, M. G.; Lehtonen, S

    2012-01-01

    Podocytes are insulin-sensitive and take up glucose in response to insulin. This requires nephrin, which interacts with vesicle-associated membrane protein 2 (VAMP2) on GLUT4 storage vesicles (GSVs) and facilitates their fusion with the plasma membrane. In this paper, we show that the filament-forming GTPase septin 7 is expressed in podocytes and associates with CD2-associated protein (CD2AP) and nephrin, both essential for glomerular ultrafiltration. In addition, septin 7 coimmunoprecipitate...

  6. Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in dopaminergic neurons.

    Science.gov (United States)

    Son, Jin H; Kawamata, Hibiki; Yoo, Myung S; Kim, Dae J; Lee, Young K; Kim, Sooyoul; Dawson, Ted M; Zhang, Hui; Sulzer, David; Yang, Lichuan; Beal, M Flint; Degiorgio, Lorraine A; Chun, Hong S; Baker, Harriet; Peng, Chu

    2005-08-01

    Septin 5, a parkin substrate, is a vesicle- and membrane-associated protein that plays a significant role in inhibiting exocytosis. The regulatory function of Septin 5 in dopaminergic (DAergic) neurons of substantia nigra (SN), maintained at relatively low levels, has not yet been delineated. As loss of function mutations of parkin are the principal cause of a familial Parkinson's disease, a prevailing hypothesis is that the loss of parkin activity results in accumulation of Septin 5 which confers neuron-specific toxicity in SN-DAergic neurons. In vitro and in vivo models were used to support this hypothesis. In our well-characterized DAergic SN4741 cell model, acute accumulation of elevated levels of Septin 5, but not synphilin-1 (another parkin substrate), resulted in cytotoxic cell death that was markedly reduced by parkin co-transfection. A transgenic mouse model expressing a dominant negative parkin mutant accumulated moderate levels of Septin 5 in SN-DAergic neurons. These mice acquired a progressive l-DOPA responsive motor dysfunction that developed despite a 25% higher than normal level of striatal dopamine (DA) and no apparent loss of DAergic neurons. The phenotype of this animal, increased striatal dopamine and reduced motor function, was similar to that observed in parkin knockout animals, suggesting a common DAergic alteration. These data suggest that a threshold level of Septin 5 accumulation is required for DAergic cell loss and that l-DOPA-responsive motor deficits can occur even in the presence of elevated DA.

  7. SEPT14 Is Associated with a Reduced Risk for Parkinson's Disease and Expressed in Human Brain.

    Science.gov (United States)

    Rozenkrantz, Liron; Gan-Or, Ziv; Gana-Weisz, Mali; Mirelman, Anat; Giladi, Nir; Bar-Shira, Anat; Orr-Urtreger, Avi

    2016-07-01

    Genes involved in cytoskeletal stability and trafficking, such as MAPT and SNCA, are important risk factors for Parkinson's disease (PD). Two members of the cytoskeletal Septin family, SEPT4 and SEPT5, were implicated in PD pathobiology. We aimed to determine whether Septin genes are associated with Parkinson's disease. To this end, six SNPs located in four different Septin loci were analyzed in 720 PD patients and 740 controls, all of Ashkenazi-Jewish origin. In addition, SEPT14 was sequenced and its expression was determined in different human tissues. Our results revealed that two SNPs in the SEPT14 locus, rs11981883 and rs10241628, were associated with a reduced risk for PD (p = 0.02 and p = 0.005). A third SNP, rs77231105, was localized in the putative promoter of SEPT14 and was predicted to affect the binding of the transcription factor Nkx2.5. This SNP was also associated with a reduced risk for PD (OR = 0.28, p Parkinson's disease pathogenesis, yet more studies are necessary to validate these results.

  8. Health implications of human trafficking.

    Science.gov (United States)

    Richards, Tiffany A

    2014-01-01

    Freedom is arguably the most cherished right in the United States. But each year, approximately 14,500 to 17,500 women, men and children are trafficked into the United States for the purposes of forced labor or sexual exploitation. Human trafficking has significant effects on both physical and mental health. This article describes the features of human trafficking, its physical and mental health effects and the vital role nurses can play in providing care to this vulnerable population.

  9. Septin 8 is an interaction partner and in vitro substrate of MK5

    Institute of Scientific and Technical Information of China (English)

    Alexey; Shiryaev; Sergiy; Kostenko; Gianina; Dumitriu; Ugo; Moens

    2012-01-01

    AIM:To identify novel substrates for the mitogen-activated protein kinase-activated protein kinase 5(MK5).METHODS:Yeast two-hybrid screening with MK5 as bait was used to identify novel possible interaction partners.The binding of putative partner was further examined by glutathione S-transferase(GST) pull-down,co-immunoprecipitation and fluorescence resonance energy transfer(FRET) analysis.In vitro kinase and peptide array assays were used to map MK5 phosphoacceptor sites on the new partner.Confocal microscopy was performed to study the subcellular localization of MK5 and its partners.RESULTS:Septin 8 was identified as a novel interaction partner for MK5 by yeast two-hybrid screening.This interaction was confirmed by GST pull-down,coimmunoprecipitation and FRET analysis.Septin 5,which can form a complex with septin 8,did not interact with MK5.Serine residues 242 and 271 on septin 8 were identified as in vitro MK5 phosphorylation sites.MK5 and septin 8 co-localized in the perinuclear area and in cell protrusions.Moreover,both proteins co-localized with vesicle marker synaptophysin.

  10. Implications of interaction between Humans and Structures

    DEFF Research Database (Denmark)

    Pedersen, Lars

    2015-01-01

    as structural damping and therefore also structural vibration levels). The paper addresses this subject and explores implications of having passive humans present on the structure. In experimental tests with a laboratory floor it is examined to which degree the posture of humans passively sitting on the floor......Many civil engineering structures are occupied by humans, and often humans are considered as a static load in calculations. However, active humans on structures can cause structural vibrations. Passive humans might also be present on that structure and they do change the structural system (such...... influences the damping added to the floor. A numerical case study explores how passive humans may influence vibration levels of a floor....

  11. Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV

    Science.gov (United States)

    Akil, Abdellah; Peng, Juan; Omrane, Mohyeddine; Gondeau, Claire; Desterke, Christophe; Marin, Mickaël; Tronchère, Hélène; Taveneau, Cyntia; Sar, Sokhavuth; Briolotti, Philippe; Benjelloun, Soumaya; Benjouad, Abdelaziz; Maurel, Patrick; Thiers, Valérie; Bressanelli, Stéphane; Samuel, Didier; Bréchot, Christian; Gassama-Diagne, Ama

    2016-01-01

    The accumulation of lipid droplets (LD) is frequently observed in hepatitis C virus (HCV) infection and represents an important risk factor for the development of liver steatosis and cirrhosis. The mechanisms of LD biogenesis and growth remain open questions. Here, transcriptome analysis reveals a significant upregulation of septin 9 in HCV-induced cirrhosis compared with the normal liver. HCV infection increases septin 9 expression and induces its assembly into filaments. Septin 9 regulates LD growth and perinuclear accumulation in a manner dependent on dynamic microtubules. The effects of septin 9 on LDs are also dependent on binding to PtdIns5P, which, in turn, controls the formation of septin 9 filaments and its interaction with microtubules. This previously undescribed cooperation between PtdIns5P and septin 9 regulates oleate-induced accumulation of LDs. Overall, our data offer a novel route for LD growth through the involvement of a septin 9/PtdIns5P signalling pathway. PMID:27417143

  12. Implications of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Kitcher, P.

    1998-11-01

    The Human Genome Project (HGP), launched in 1991, aims to map and sequence the human genome by 2006. During the fifteen-year life of the project, it is projected that $3 billion in federal funds will be allocated to it. The ultimate aims of spending this money are to analyze the structure of human DNA, to identify all human genes, to recognize the functions of those genes, and to prepare for the biology and medicine of the twenty-first century. The following summary examines some of the implications of the program, concentrating on its scientific import and on the ethical and social problems that it raises. Its aim is to expose principles that might be used in applying the information which the HGP will generate. There is no attempt here to translate the principles into detailed proposals for legislation. Arguments and discussion can be found in the full report, but, like this summary, that report does not contain any legislative proposals.

  13. Matrix Stiffness Regulates Endothelial Cell Proliferation through Septin 9

    Science.gov (United States)

    Yeh, Yi-Ting; Hur, Sung Sik; Chang, Joann; Wang, Kuei-Chun; Chiu, Jeng-Jiann; Li, Yi-Shuan; Chien, Shu

    2012-01-01

    Endothelial proliferation, which is an important process in vascular homeostasis, can be regulated by the extracellular microenvironment. In this study we demonstrated that proliferation of endothelial cells (ECs) was enhanced on hydrogels with high stiffness (HSG, 21.5 kPa) in comparison to those with low stiffness (LSG, 1.72 kPa). ECs on HSG showed markedly prominent stress fibers and a higher RhoA activity than ECs on LSG. Blockade of RhoA attenuated stress fiber formation and proliferation of ECs on HSG, but had little effect on ECs on LSG; enhancement of RhoA had opposite effects. The phosphorylations of Src and Vav2, which are positive RhoA upstream effectors, were higher in ECs on HSG. The inhibition of Src/Vav2 attenuated the HSG-mediated RhoA activation and EC proliferation but exhibited nominal effects on ECs on LSG. Septin 9 (SEPT9), the negative upstream effector for RhoA, was significantly higher in ECs on LSG. The inhibition of SEPT9 increased RhoA activation, Src/Vav2 phosphorylations, and EC proliferation on LSG, but showed minor effects on ECs on HSG. We further demonstrated that the inactivation of integrin αvβ3 caused an increase of SEPT9 expression in ECs on HSG to attenuate Src/Vav2 phosphorylations and inhibit RhoA-dependent EC proliferation. These results demonstrate that the SEPT9/Src/Vav2/RhoA pathway constitutes an important molecular mechanism for the mechanical regulation of EC proliferation. PMID:23118862

  14. Matrix stiffness regulates endothelial cell proliferation through septin 9.

    Directory of Open Access Journals (Sweden)

    Yi-Ting Yeh

    Full Text Available Endothelial proliferation, which is an important process in vascular homeostasis, can be regulated by the extracellular microenvironment. In this study we demonstrated that proliferation of endothelial cells (ECs was enhanced on hydrogels with high stiffness (HSG, 21.5 kPa in comparison to those with low stiffness (LSG, 1.72 kPa. ECs on HSG showed markedly prominent stress fibers and a higher RhoA activity than ECs on LSG. Blockade of RhoA attenuated stress fiber formation and proliferation of ECs on HSG, but had little effect on ECs on LSG; enhancement of RhoA had opposite effects. The phosphorylations of Src and Vav2, which are positive RhoA upstream effectors, were higher in ECs on HSG. The inhibition of Src/Vav2 attenuated the HSG-mediated RhoA activation and EC proliferation but exhibited nominal effects on ECs on LSG. Septin 9 (SEPT9, the negative upstream effector for RhoA, was significantly higher in ECs on LSG. The inhibition of SEPT9 increased RhoA activation, Src/Vav2 phosphorylations, and EC proliferation on LSG, but showed minor effects on ECs on HSG. We further demonstrated that the inactivation of integrin α(vβ(3 caused an increase of SEPT9 expression in ECs on HSG to attenuate Src/Vav2 phosphorylations and inhibit RhoA-dependent EC proliferation. These results demonstrate that the SEPT9/Src/Vav2/RhoA pathway constitutes an important molecular mechanism for the mechanical regulation of EC proliferation.

  15. Septins are important for cell polarity, septation and asexual spore formation in Neurospora crassa and show different patterns of localisation at germ tube tips.

    Directory of Open Access Journals (Sweden)

    Adokiye Berepiki

    Full Text Available Septins are GTP-binding cytoskeletal proteins that contribute to cell polarity, vesicle trafficking, cytokinesis and cell morphogenesis. Here we have characterised the six septins encoded by the genome of the model filamentous fungus Neurospora crassa. Analysis of septin null mutants demonstrated that septins limit the sites of emergence of germ tubes and are important for septation and conidiation in N. crassa. Septins constituted a range of different higher-order structures in N. crassa - rings, loops, fibres, bands, and caps - which can co-exist within the same cell. They showed different patterns of localisation at germ tube tips, with GFP-CDC-10 and CDC-11-GFP forming a subapical collar with lower signal intensity at the tip apex, CDC-3-GFP and CDC-12-GFP organized as a cap at the tip apex and GFP-ASP-1 forming an extended subapical collar. Purification of the septin complex and mass spectrometry of isolated proteins revealed that the septin complex consists predominantly of CDC-3, CDC-10, CDC-11 and CDC-12. Immunoprecipitation of the putative septin ASP-1 revealed that this protein interacts with the core septin complex.

  16. SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.

    Science.gov (United States)

    Jian, Wenjing; Zhong, Lin; Wen, Jing; Tang, Yao; Qiu, Bo; Wu, Ziqing; Yan, Jinhai; Zhou, Xinhua; Zhao, Tong

    2015-01-01

    Hodgkin's lymphoma (HL) is a lymphoid neoplasm characterized by Hodgkin's and Reed-Sternberg (H/RS) cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20) into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin's lymphoma (cHL) cells (L428) into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2) in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.

  17. SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.

    Directory of Open Access Journals (Sweden)

    Wenjing Jian

    Full Text Available Hodgkin's lymphoma (HL is a lymphoid neoplasm characterized by Hodgkin's and Reed-Sternberg (H/RS cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20 into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin's lymphoma (cHL cells (L428 into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS, we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2 in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.

  18. Genetic deletion of SEPT7 reveals a cell type-specific role of septins in microtubule destabilization for the completion of cytokinesis.

    Directory of Open Access Journals (Sweden)

    Manoj B Menon

    2014-08-01

    Full Text Available Cytokinesis terminates mitosis, resulting in separation of the two sister cells. Septins, a conserved family of GTP-binding cytoskeletal proteins, are an absolute requirement for cytokinesis in budding yeast. We demonstrate that septin-dependence of mammalian cytokinesis differs greatly between cell types: genetic loss of the pivotal septin subunit SEPT7 in vivo reveals that septins are indispensable for cytokinesis in fibroblasts, but expendable in cells of the hematopoietic system. SEPT7-deficient mouse embryos fail to gastrulate, and septin-deficient fibroblasts exhibit pleiotropic defects in the major cytokinetic machinery, including hyperacetylation/stabilization of microtubules and stalled midbody abscission, leading to constitutive multinucleation. We identified the microtubule depolymerizing protein stathmin as a key molecule aiding in septin-independent cytokinesis, demonstrated that stathmin supplementation is sufficient to override cytokinesis failure in SEPT7-null fibroblasts, and that knockdown of stathmin makes proliferation of a hematopoietic cell line sensitive to the septin inhibitor forchlorfenuron. Identification of septin-independent cytokinesis in the hematopoietic system could serve as a key to identify solid tumor-specific molecular targets for inhibition of cell proliferation.

  19. Rapid redistribution of phosphatidylinositol-(4,5)-bisphosphate and septins during the Candida albicans response to caspofungin.

    Science.gov (United States)

    Badrane, Hassan; Nguyen, M Hong; Blankenship, Jill R; Cheng, Shaoji; Hao, Binghua; Mitchell, Aaron P; Clancy, Cornelius J

    2012-09-01

    We previously showed that phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and septin regulation play major roles in maintaining Candida albicans cell wall integrity in response to caspofungin and other stressors. Here, we establish a link between PI(4,5)P2 signaling and septin localization and demonstrate that rapid redistribution of PI(4,5)P2 and septins is part of the natural response of C. albicans to caspofungin. First, we studied caspofungin-hypersusceptible C. albicans irs4 and inp51 mutants, which have elevated PI(4,5)P2 levels due to loss of PI(4,5)P2-specific 5'-phosphatase activity. PI(4,5)P2 accumulated in discrete patches, rather than uniformly, along surfaces of mutants in yeast and filamentous morphologies, as visualized with a green fluorescent protein (GFP)-pleckstrin homology domain. The patches also contained chitin (calcofluor white staining) and cell wall protein Rbt5 (Rbt5-GFP). By transmission electron microscopy, patches corresponded to plasma membrane invaginations that incorporated cell wall material. Fluorescently tagged septins Cdc10 and Sep7 colocalized to these sites, consistent with well-described PI(4,5)P2-septin physical interactions. Based on expression patterns of cell wall damage response genes, irs4 and inp51 mutants were firmly positioned within a group of caspofungin-hypersusceptible, septin-regulatory protein kinase mutants. irs4 and inp51 were linked most closely to the gin4 mutant by expression profiling, PI(4,5)P2-septin-chitin redistribution and other phenotypes. Finally, sublethal 5-min exposure of wild-type C. albicans to caspofungin resulted in redistribution of PI(4,5)P2 and septins in a manner similar to those of irs4, inp51, and gin4 mutants. Taken together, our data suggest that the C. albicans Irs4-Inp51 5'-phosphatase complex and Gin4 function upstream of PI(4,5)P2 and septins in a pathway that helps govern responses to caspofungin.

  20. The septin AspB in Aspergillus nidulans forms bars and filaments and plays roles in growth emergence and conidiation.

    Science.gov (United States)

    Hernández-Rodríguez, Yainitza; Hastings, Susan; Momany, Michelle

    2012-03-01

    In yeast, septins form rings at the mother-bud neck and function as diffusion barriers. In animals, septins form filaments that can colocalize with other cytoskeletal elements. In the filamentous fungus Aspergillus nidulans there are five septin genes, aspA (an ortholog of Saccharomyces cerevisiae CDC11), aspB (an ortholog of S. cerevisiae CDC3), aspC (an ortholog of S. cerevisiae CDC12), aspD (an ortholog of S. cerevisiae CDC10), and aspE (found only in filamentous fungi). The aspB gene was previously reported to be the most highly expressed Aspergillus nidulans septin and to be essential. Using improved gene targeting techniques, we found that deletion of aspB is not lethal but results in delayed septation, increased emergence of germ tubes and branches, and greatly reduced conidiation. We also found that AspB-green fluorescent protein (GFP) localizes as rings and collars at septa, branches, and emerging layers of the conidiophore and as bars and filaments in conidia and hyphae. Bars are found in dormant and isotropically expanding conidia and in subapical nongrowing regions of hyphae and display fast movements. Filaments form as the germ tube emerges, localize to hyphal and branch tips, and display slower movements. All visible AspB-GFP structures are retained in ΔaspD and lost in ΔaspA and ΔaspC strains. Interestingly, in the ΔaspE mutant, AspB-GFP rings, bars, and filaments are visible in early growth, but AspB-GFP rods and filaments disappear after septum formation. AspE orthologs are only found in filamentous fungi, suggesting that this class of septins might be required for stability of septin bars and filaments in highly polar cells.

  1. Identification of an amphipathic helix important for the formation of ectopic septin spirals and axial budding in yeast axial landmark protein Bud3p.

    Science.gov (United States)

    Guo, Jia; Gong, Ting; Gao, Xiang-Dong

    2011-03-08

    Correct positioning of polarity axis in response to internal or external cues is central to cellular morphogenesis and cell fate determination. In the budding yeast Saccharomyces cerevisiae, Bud3p plays a key role in the axial bud-site selection (axial budding) process in which cells assemble the new bud next to the preceding cell division site. Bud3p is thought to act as a component of a spatial landmark. However, it is not clear how Bud3p interacts with other components of the landmark, such as the septins, to control axial budding. Here, we report that overexpression of Bud3p causes the formation of small septin rings (∼1 µm in diameter) and arcs aside from previously reported spiral-like septin structures. Bud3p closely associates with the septins in vivo as Bud3p colocalizes with these aberrant septin structures and forms a complex with two septins, Cdc10p and Cdc11p. The interaction of Bud3p with the septins may involve multiple regions of Bud3p including 1-858, 850-1220, and 1221-1636 a.a. since they all target to the bud neck but exhibit different effects on septin organization when overexpressed. In addition, our study reveals that the axial budding function of Bud3p is mediated by the N-terminal region 1-858. This region shares an amphipathic helix (850-858) crucial for bud neck targeting with the middle portion 850-1103 involved in the formation of ectopic septin spirals and rings. Interestingly, the Dbl-homology domain located in 1-858 is dispensable for axial bud-site selection. Our findings suggest that multiple regions of Bud3p ensure efficient targeting of Bud3p to the bud neck in the assembly of the axial landmark and distinct domains of Bud3p are involved in axial bud-site selection and other cellular processes.

  2. The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans

    Science.gov (United States)

    Thevissen, Karin; de Mello Tavares, Patricia; Xu, Deming; Blankenship, Jill; Vandenbosch, Davy; Idkowiak-Baldys, Jolanta; Govaert, Gilmer; Bink, Anna; Rozental, Sonia; de Groot, Piet W.J.; Davis, Talya R.; Kumamoto, Carol A.; Vargas, Gabriele; Nimrichter, Leonardo; Coenye, Tom; Mitchell, Aaron; Roemer, Terry; Hannun, Yusuf A.; Cammue, Bruno P.A.

    2012-01-01

    Summary The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2,868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes was involved in cell wall integrity and hyphal growth/septin ring formation. Consistent with these genetic data, we demonstrated that RsAFP2 interacts with the cell wall of C. albicans, which also contains glucosylceramides, and activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces mislocalization of septins and blocks the yeast-to-hypha transition in C. albicans. Increased ceramide levels have previously been shown to result in apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans membranes were analyzed following RsAFP2 treatment and, as expected, increased accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans cells was detected. This is the first report on the interaction of a plant defensin with glucosylceramides in the fungal cell wall, causing cell wall stress, and on the effects of a defensin on septin localization and ceramide accumulation. PMID:22384976

  3. Open Marriage: Implications for Human Service Systems

    Science.gov (United States)

    O'Neill, Nena; O'Neill, George

    1973-01-01

    The authors of Open Marriage reiterate the meaning and possibilities of the open marriage concept and advance suggestions for change in the areas of residence, work, child care, and educational patterns. Human service systems must search out the universal values to be maintained in all human relationships. (Editor)

  4. The human implications of management reengineering

    OpenAIRE

    Ion VERBONCU; Aurel MANOLESCU

    2008-01-01

    Redesigning corporate management represents the most important means of managerial change and has a variety of consequences – economic, social, human etc. Expressed in terms of remodeling the methodological, organizational, decision-making and informational components of the management system, management reengineering generates substantial changes in the implementation of managerial functions and, implicitly, significant managerial and economic performances. Moreover, managerial redesign make...

  5. Security Implications of Human-Trafficking Networks

    Science.gov (United States)

    2007-06-15

    to those security concerns. Background How is Human Trafficking Carried Out? While trafficking victims are often found in sweatshops , domestic...labor. This type of trafficking is often found in agricultural labor, the production of goods (typically called sweatshops ) and construction labor

  6. Helminth genomics: The implications for human health.

    Directory of Open Access Journals (Sweden)

    Paul J Brindley

    Full Text Available More than two billion people (one-third of humanity are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings.

  7. Metals in cosmetics: implications for human health.

    Science.gov (United States)

    Borowska, Sylwia; Brzóska, Malgorzata M

    2015-06-01

    Cosmetics, preparations repeatedly applied directly to the human skin, mucous membranes, hair and nails, should be safe for health, however, recently there has been increasing concern about their safety. Unfortunately, using these products in some cases is related to the occurrence of unfavourable effects resulting from intentional or the accidental presence of chemical substances, including toxic metals. Heavy metals such as lead, mercury, cadmium, arsenic and nickel, as well as aluminium, classified as a light metal, are detected in various types of cosmetics (colour cosmetics, face and body care products, hair cosmetics, herbal cosmetics, etc.). In addition, necessary, but harmful when they occur in excessive amounts, elements such as copper, iron, chromium and cobalt are also present in cosmetic products. Metals occurring in cosmetics may undergo retention and act directly in the skin or be absorbed through the skin into the blood, accumulate in the body and exert toxic effects in various organs. Some cases of topical (mainly allergic contact dermatitis) and systemic effects owing to exposure to metals present in cosmetics have been reported. Literature data show that in commercially available cosmetics toxic metals may be present in amounts creating a danger to human health. Thus, the present review article focused on the problems related to the presence of heavy metals and aluminium in cosmetics, including their sources, concentrations and law regulations as well as danger for the health of these products users. Owing to the growing usage of cosmetics it is necessary to pay special attention to these problems.

  8. Human RAG mutations: biochemistry and clinical implications.

    Science.gov (United States)

    Notarangelo, Luigi D; Kim, Min-Sung; Walter, Jolan E; Lee, Yu Nee

    2016-04-01

    The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate the V(D)J recombination process, which ultimately enables the generation of T cells and B cells with a diversified repertoire of antigen-specific receptors. Mutations of the RAG genes in humans are associated with a broad spectrum of clinical phenotypes, ranging from severe combined immunodeficiency to autoimmunity. Recently, novel insights into the phenotypic diversity of this disease have been provided by resolving the crystal structure of the RAG complex, by developing novel assays to test recombination activity of the mutant RAG proteins and by characterizing the molecular and cellular basis of immune dysregulation in patients with RAG deficiency.

  9. Unraveling the equine lymphocyte proteome: differential septin 7 expression associates with immune cells in equine recurrent uveitis.

    Science.gov (United States)

    Degroote, Roxane L; Hauck, Stefanie M; Amann, Barbara; Hirmer, Sieglinde; Ueffing, Marius; Deeg, Cornelia A

    2014-01-01

    Equine recurrent uveitis is a spontaneous, lymphocyte-driven autoimmune disease. It affects horses worldwide and presents with painful remitting-relapsing inflammatory attacks of inner eye structures eventually leading to blindness. Since lymphocytes are the key players in equine recurrent uveitis, we were interested in potential changes of their protein repertoire which may be involved in disease pathogenesis. To create a reference for differential proteome analysis, we first unraveled the equine lymphocyte proteome by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequently identified 352 protein spots. Next, we compared lymphocytes from ERU cases and healthy horses with a two-dimensional fluorescence difference in gel electrophoresis approach. With this technique, we identified seven differentially expressed proteins between conditions. One of the significantly lower expressed candidates, septin 7, plays a role in regulation of cell shape, motility and migration. Further analyses revealed T cells as the main cell type with decreased septin 7 abundance in equine recurrent uveitis. These findings point to a possible pathogenetic role of septin 7 in this sight-threatening disease.

  10. Unraveling the equine lymphocyte proteome: differential septin 7 expression associates with immune cells in equine recurrent uveitis.

    Directory of Open Access Journals (Sweden)

    Roxane L Degroote

    Full Text Available Equine recurrent uveitis is a spontaneous, lymphocyte-driven autoimmune disease. It affects horses worldwide and presents with painful remitting-relapsing inflammatory attacks of inner eye structures eventually leading to blindness. Since lymphocytes are the key players in equine recurrent uveitis, we were interested in potential changes of their protein repertoire which may be involved in disease pathogenesis. To create a reference for differential proteome analysis, we first unraveled the equine lymphocyte proteome by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequently identified 352 protein spots. Next, we compared lymphocytes from ERU cases and healthy horses with a two-dimensional fluorescence difference in gel electrophoresis approach. With this technique, we identified seven differentially expressed proteins between conditions. One of the significantly lower expressed candidates, septin 7, plays a role in regulation of cell shape, motility and migration. Further analyses revealed T cells as the main cell type with decreased septin 7 abundance in equine recurrent uveitis. These findings point to a possible pathogenetic role of septin 7 in this sight-threatening disease.

  11. Theory Development and Convergence of Human Resource Fields: Implications for Human Performance Technology

    Science.gov (United States)

    Cho, Yonjoo; Yoon, Seung Won

    2010-01-01

    This study examines major theory developments in human resource (HR) fields and discusses implications for human performance technology (HPT). Differentiated HR fields are converging to improve organizational performance through knowledge-based innovations. Ruona and Gibson (2004) made a similar observation and analyzed the historical evolution…

  12. Theory Development and Convergence of Human Resource Fields: Implications for Human Performance Technology

    Science.gov (United States)

    Cho, Yonjoo; Yoon, Seung Won

    2010-01-01

    This study examines major theory developments in human resource (HR) fields and discusses implications for human performance technology (HPT). Differentiated HR fields are converging to improve organizational performance through knowledge-based innovations. Ruona and Gibson (2004) made a similar observation and analyzed the historical evolution…

  13. Budding yeast dma proteins control septin dynamics and the spindle position checkpoint by promoting the recruitment of the Elm1 kinase to the bud neck.

    Science.gov (United States)

    Merlini, Laura; Fraschini, Roberta; Boettcher, Barbara; Barral, Yves; Lucchini, Giovanna; Piatti, Simonetta

    2012-01-01

    The first step towards cytokinesis in budding yeast is the assembly of a septin ring at the future site of bud emergence. Integrity of this ring is crucial for cytokinesis, proper spindle positioning, and the spindle position checkpoint (SPOC). This checkpoint delays mitotic exit and cytokinesis as long as the anaphase spindle does not properly align with the division axis. SPOC signalling requires the Kin4 protein kinase and the Kin4-regulating Elm1 kinase, which also controls septin dynamics. Here, we show that the two redundant ubiquitin-ligases Dma1 and Dma2 control septin dynamics and the SPOC by promoting the efficient recruitment of Elm1 to the bud neck. Indeed, dma1 dma2 mutant cells show reduced levels of Elm1 at the bud neck and Elm1-dependent activation of Kin4. Artificial recruitment of Elm1 to the bud neck of the same cells is sufficient to re-establish a normal septin ring, proper spindle positioning, and a proficient SPOC response in dma1 dma2 cells. Altogether, our data indicate that septin dynamics and SPOC function are intimately linked and support the idea that integrity of the bud neck is crucial for SPOC signalling.

  14. Budding yeast dma proteins control septin dynamics and the spindle position checkpoint by promoting the recruitment of the Elm1 kinase to the bud neck.

    Directory of Open Access Journals (Sweden)

    Laura Merlini

    Full Text Available The first step towards cytokinesis in budding yeast is the assembly of a septin ring at the future site of bud emergence. Integrity of this ring is crucial for cytokinesis, proper spindle positioning, and the spindle position checkpoint (SPOC. This checkpoint delays mitotic exit and cytokinesis as long as the anaphase spindle does not properly align with the division axis. SPOC signalling requires the Kin4 protein kinase and the Kin4-regulating Elm1 kinase, which also controls septin dynamics. Here, we show that the two redundant ubiquitin-ligases Dma1 and Dma2 control septin dynamics and the SPOC by promoting the efficient recruitment of Elm1 to the bud neck. Indeed, dma1 dma2 mutant cells show reduced levels of Elm1 at the bud neck and Elm1-dependent activation of Kin4. Artificial recruitment of Elm1 to the bud neck of the same cells is sufficient to re-establish a normal septin ring, proper spindle positioning, and a proficient SPOC response in dma1 dma2 cells. Altogether, our data indicate that septin dynamics and SPOC function are intimately linked and support the idea that integrity of the bud neck is crucial for SPOC signalling.

  15. Recent genetic discoveries implicating ion channels in human cardiovascular diseases.

    Science.gov (United States)

    George, Alfred L

    2014-04-01

    The term 'channelopathy' refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.

  16. Reactive oxygen species and vascular biology: implications in human hypertension.

    Science.gov (United States)

    Touyz, Rhian M; Briones, Ana M

    2011-01-01

    Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension.

  17. 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.

  18. Absence of annulus in human asthenozoospermia: case report.

    Science.gov (United States)

    Lhuillier, P; Rode, B; Escalier, D; Lorès, P; Dirami, T; Bienvenu, T; Gacon, G; Dulioust, E; Touré, A

    2009-06-01

    The annulus is a septin-based ring structure located at the junction of the midpiece (MP) and the principal piece (PP) of spermatozoa flagellum. In the mouse, deletion of Septin 4, a structural component of the sperm annulus, prevents annulus formation and leads to MP-PP disjunction, flagellar bending, asthenozoospermia and male sterility. Testis anion transporter 1 (Tat1) is a germ cell-specific member of the SLC26 anion transporter family and is co-expressed with Septin 4 at the sperm annulus. Interestingly, Tat1 null sperm bear an atrophic annulus, causing a phenotype similar to that of Sept4 null sperm. We searched for Tat1 misexpression and/or mislocalization in spermatozoa from asthenozoospermic subjects (n = 75) and controls by performing an immunofluorescence detection assay on sperm smear preparations. We found one patient showing moderate asthenozoospermia, with 97% of sperm lacking Tat1, Septin 4 and Septin 7 proteins at the annulus. We confirmed the absence of the annulus structure by transmission electron microscopy and observed that spermatozoa from the patient displayed MP-PP disjunction and abnormal mitochondrial organization. We show that the structural defects in sperm are not caused by abnormal transcription or point mutations of the TAT1 and SEPT4 genes; however, although both proteins are expressed, they are not properly localized at sperm annulus. The case we studied, so far unreported in human, confirms the involvement of Tat1 and Septin proteins in the constitution of the annulus, but also raises questions about the function of this structure in human sperm motility.

  19. Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

    Directory of Open Access Journals (Sweden)

    Adjimon Gatien Lokossou

    2014-11-01

    Full Text Available Human endogenous retroviruses (ERVs represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs, a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia.

  20. Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay.

    Directory of Open Access Journals (Sweden)

    Robert Grützmann

    Full Text Available BACKGROUND: Colorectal cancer (CRC is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. METHODOLOGY/PRINCIPAL FINDINGS: Using a PCR assay for analysis of Septin 9 (SEPT9 hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls. 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48% and 7/102 controls (7%. In the test study 73/126 CRCs (58% and 18/183 control samples (10% were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected while maintaining 90% specificity (19/183 for controls. Positive rates for plasmas from the other cancers (11/96 and non-cancerous conditions (41/315 were low. The rate of polyp detection (>1 cm was approximately 20%. CONCLUSIONS/SIGNIFICANCE: Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted.

  1. The planar cell polarity effector protein Wdpcp (Fritz) controls epithelial cell cortex dynamics via septins and actomyosin.

    Science.gov (United States)

    Park, Tae Joo; Kim, Su Kyoung; Wallingford, John B

    2015-01-09

    Planar cell polarity (PCP) signaling controls polarized behaviors in diverse tissues, including the collective cell movements of gastrulation and the planar polarized beating of motile cilia. A major question in PCP signaling concerns the mechanisms linking this signaling cascade with more general cytoskeletal elements to drive polarized behavior. Previously, we reported that the PCP effector protein Wdpcp (formerly known as Fritz) interacts with septins and is critical for collective cell migration and cilia formation. Here, we report that Wdpcp is broadly involved in maintaining cortical tension in epithelial cells. In vivo 3D time-lapse imaging revealed that Wdpcp is necessary for basolateral plasma membrane stability in epithelial tissues, and we further show that Wdpcp controls cortical septin localization to maintain cortical rigidity in mucociliary epithelial cells. Finally, we show that Wdpcp acts via actomyosin to maintain balanced cortical tension in the epithelium. These data suggest that, in addition to its role in controlling plasma membrane dynamics in collective mesenchymal cell movements, Wdpcp is also essential for normal cell cortex stability during epithelial homeostasis.

  2. Is Homo sapiens polytypic? Human taxonomic diversity and its implications.

    Science.gov (United States)

    Woodley, Michael A

    2010-01-01

    The term race is a traditional synonym for subspecies, however it is frequently asserted that Homo sapiens is monotypic and that what are termed races are nothing more than biological illusions. In this manuscript a case is made for the hypothesis that H. sapiens is polytypic, and in this way is no different from other species exhibiting similar levels of genetic and morphological diversity. First it is demonstrated that the four major definitions of race/subspecies can be shown to be synonymous within the context of the framework of race as a correlation structure of traits. Next the issue of taxonomic classification is considered where it is demonstrated that H. sapiens possesses high levels morphological diversity, genetic heterozygosity and differentiation (F(ST)) compared to many species that are acknowledged to be polytypic with respect to subspecies. Racial variation is then evaluated in light of the phylogenetic species concept, where it is suggested that the least inclusive monophyletic units exist below the level of species within H. sapiens indicating the existence of a number of potential human phylogenetic species; and the biological species concept, where it is determined that racial variation is too small to represent differentiation at the level of biological species. Finally the implications of this are discussed in the context of anthropology where an accurate picture of the sequence and timing of events during the evolution of human taxa are required for a complete picture of human evolution, and medicine, where a greater appreciation of the role played by human taxonomic differences in disease susceptibility and treatment responsiveness will save lives in the future.

  3. Seasonal variations in physical activity and implications for human health.

    Science.gov (United States)

    Shephard, Roy J; Aoyagi, Yukitoshi

    2009-10-01

    This review explores the implications of seasonal changes in physical activity for fitness and human health. Photosensitivity and nutrient shortages mediate animal hibernation via the hypothalamus and changes in leptin and ghrelin concentrations. Opportunities for hunting and crop cultivation determine seasonal activity in under-developed human societies, but in developed societies temperature and rainfall are dominant influences, usually over-riding innate rhythms. Both questionnaire data and objective measurements show that many groups from children to the elderly increase their physical activity from winter to spring or summer. Measurements of maximal oxygen intake and muscle strength commonly show parallel seasonal changes. However, potential effects upon body mass and body fat may be counteracted by changes of food intake; subsistence agriculturists sometimes maintain or increase physical activity at the expense of a decrease in body mass. In developed societies, body fat commonly increases during the winter, with parallel changes in blood lipids, blood pressure and blood coagulability; moreover, these changes are not always fully reversed the following summer. Most developed societies show increased all-cause and cardiac mortalities in the winter. Health consequences of seasonal variations in physical activity including an increased vulnerability to cardiac catastrophe and a year-by-year increase in total body fat seem most likely if the average level of physical activity for the year is low. Public health recommendations should underline the importance of maintaining physical activity during adverse environmental conditions by adapting clothing, modifying behaviour and exploiting any available air-conditioned indoor facilities.

  4. Cigarette smoke toxins deposited on surfaces: implications for human health.

    Directory of Open Access Journals (Sweden)

    Manuela Martins-Green

    Full Text Available Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered - Thirdhand smoke (THS - the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker similar to those found in children exposed to SHS (and consequently to THS. In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.

  5. Thermotolerance of human myometrium: implications for minimally invasive uterine therapies

    Science.gov (United States)

    Thomas, Aaron C.; Grisez, Brian T.; McMillan, Kathleen; Chill, Nicholas; Harclerode, Tyler P.; Radabaugh, Rebecca; Jones, Ryan M.; Coad, James E.

    2013-02-01

    Endometrial ablation has gained significant clinical acceptance over the last decade as a minimally invasive treatment for abnormal uterine bleeding. To improve upon current thermal injury modeling, it is important to better characterize the myometrium's thermotolerance. The extent of myometrial thermal injury was determined across a spectrum of thermal histories/doses (time-temperature combinations). Fresh extirpated human myometrium was obtained from 13 subjects who underwent a previous scheduled benign hysterectomy. Within two hours of hysterectomy, the unfixed myometrium was treated in a stabilized saline bath with temperatures ranging from 45-70 °C and time intervals from 30- 150 seconds. The time-temperature combinations were selected to simulate treatment times under 2.5 minutes. A total of six such thermal matrices, each comprised of 45 time-temperature combinations, were prepared for evaluation. The treated myometrium was cryosectioned for nitro blue tetrazolium (NBT) staining to assess for thermal respiratory enzyme inactivation. Image analysis was subsequently used to quantitatively assess the stained myometrium's capacity to metabolize the tetrazolium at each time-temperature combination. This colorimetric data was then used as marker of cellular viability and determine survival parameters with implications for developing minimally invasive uterine therapies.

  6. Implication of human handling on packaged sausage rolls during sale

    Directory of Open Access Journals (Sweden)

    Coolborn AKHARAIYI FRED

    2016-08-01

    Full Text Available In other to identify the implication of human handling of packaged sausage rolls after production, a microbiological safety evaluation was carried out on sausage rolls sold on street and in shops. Among the sausage rolls, gala purchased from street vendors has the highest bacterial load of 2.82 × 104 CFU/g and 4.3 × 106 spore/g of fungal load, followed by meaty with bacterial load of 1.71 × 104 CFU/g and fungal load of 1.6 × 105 spore/g and was least in rite sausage roll with 1.46 × 104 CFU/g and 1 × 105 spore/g bacterial and fungal loads respectively. Seventeen bacteria species were isolated from both street vended and shop sold sausage rolls, the isolates identified including: Bacillus cereus, Acinetobacter calcoaceticus, Alcaligenes faecalis, Citrobacter freundii, Klebsiella ozaenae, Staphylococcus epidermidis, Enterobacter aerogenes, Staphylococcus aureus, Aeromonas hydrophila, Plesiomonas shigelloides, Moraxella catarhalis, Bacillus substilis, Escherichia coli, Salmonella typhi, Aeromonas anaerogenes, Aerococcus viridans and Azomonas agilis. Five fungi species were isolated from street vended sausage rolls only. The fungal species are Penicillium notatum, Aspergillus parasiticus, Aspergillus flavus, Penicillium italicum and Gliocephalis spp. From this study, street vended samples have higher microbial contamination than shop sold sausage rolls due to improper handling during sales.

  7. Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts

    Directory of Open Access Journals (Sweden)

    Fernando Calvo

    2015-12-01

    Full Text Available Cancer-associated fibroblasts (CAFs are non-cancerous cells found in solid tumors that remodel the tumor matrix and promote cancer invasion and angiogenesis. Here, we demonstrate that Cdc42EP3/BORG2 is required for the matrix remodeling, invasion, angiogenesis, and tumor-growth-promoting abilities of CAFs. Cdc42EP3 functions by coordinating the actin and septin networks. Furthermore, depletion of SEPT2 has similar effects to those of loss of Cdc42EP3, indicating a role for the septin network in the tumor stroma. Cdc42EP3 is upregulated early in fibroblast activation and precedes the emergence of the highly contractile phenotype characteristic of CAFs. Depletion of Cdc42EP3 in normal fibroblasts prevents their activation by cancer cells. We propose that Cdc42EP3 sensitizes fibroblasts to further cues—in particular, those activating actomyosin contractility—and thereby enables the generation of the pathological activated fibroblast state.

  8. Steroid synthesis by primary human keratinocytes; implications for skin disease

    Energy Technology Data Exchange (ETDEWEB)

    Hannen, Rosalind F., E-mail: r.f.hannen@qmul.ac.uk [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Michael, Anthony E. [Centre for Developmental and Endocrine Signalling, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, 3rd Floor, Lanesborough Wing, St. George' s, University of London, Cranmer Terrace, Tooting, London SW17 0RE (United Kingdom); Jaulim, Adil [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Bhogal, Ranjit [Life Science, Unilever R and D Colworth House, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Burrin, Jacky M. [Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ (United Kingdom); Philpott, Michael P. [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom)

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  9. Life-Cycle Labor Supply with Human Capital: Econometric and Behavioral Implications

    OpenAIRE

    Michael P. Keane

    2015-01-01

    I examine the econometric and behavioral implications of including human capital in the life-cycle labor supply model. With human capital, the wage no longer equals the opportunity cost of time – which is, instead, the wage plus returns to work experience. This has a number of important implications, of which I highlight four: First, labor supply elasticities become functions of both preference and wage process parameters. Thus, one cannot estimate elasticities without also specifying and est...

  10. Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans.

    Science.gov (United States)

    Badrane, Hassan; Nguyen, M Hong; Clancy, Cornelius J

    2016-06-01

    Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] activates the yeast cell wall integrity pathway. Candida albicans exposure to caspofungin results in the rapid redistribution of PI(4,5)P2 and septins to plasma membrane foci and subsequent fungicidal effects. We studied C. albicans PI(4,5)P2 and septin dynamics and protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following exposure to caspofungin and other drugs. PI(4,5)P2 and septins were visualized by live imaging of C. albicans cells coexpressing green fluorescent protein (GFP)-pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively. PI(4,5)P2 was also visualized in GFP-PH domain-expressing C. albicans mkc1 mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway activation. Fungicidal activity was assessed using 20-h time-kill assays. Caspofungin immediately induced PI(4,5)P2 and Cdc10p colocalization to aberrant foci, a process that was highly dynamic over 3 h. PI(4,5)P2 levels increased in a dose-response manner at caspofungin concentrations of ≤4× MIC and progressively decreased at concentrations of ≥8× MIC. Caspofungin exposure resulted in broad-based mother-daughter bud necks and arrested septum-like structures, in which PI(4,5)P2 and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within 10 min, peaked in response to caspofungin at 4× MIC, and declined at higher concentrations. The caspofungin-induced PI(4,5)P2 redistribution remained apparent in mkc1 mutants. Caspofungin exerted dose-dependent killing and paradoxical effects at ≤4× and ≥8× MIC, respectively. Fluconazole, amphotericin B, calcofluor white, and H2O2 did not impact the PI(4,5)P2 or Cdc10p distribution like caspofungin did. Caspofungin exerts rapid PI(4,5)P2-septin and PKC-Mkc1 responses that correlate with the extent of C. albicans killing, and the responses are not induced by other antifungal agents. PI(4,5)P2-septin regulation is crucial in early

  11. Implications of the behavioural immune system for social behaviour and human health in the modern world.

    Science.gov (United States)

    Schaller, Mark; Murray, Damian R; Bangerter, Adrian

    2015-05-26

    The 'behavioural immune system' is composed of mechanisms that evolved as a means of facilitating behaviours that minimized infection risk and enhanced fitness. Recent empirical research on human populations suggests that these mechanisms have unique consequences for many aspects of human sociality--including sexual attitudes, gregariousness, xenophobia, conformity to majority opinion and conservative sociopolitical attitudes. Throughout much of human evolutionary history, these consequences may have had beneficial health implications; but health implications in modern human societies remain unclear. This article summarizes pertinent ways in which modern human societies are similar to and different from the ecologies within which the behavioural immune system evolved. By attending to these similarities and differences, we identify a set of plausible implications-both positive and negative-that the behavioural immune system may have on health outcomes in contemporary human contexts. We discuss both individual-level infection risk and population-level epidemiological outcomes. We also discuss a variety of additional implications, including compliance with public health policies, the adoption of novel therapeutic interventions and actual immunological functioning. Research on the behavioural immune system, and its implications in contemporary human societies, can provide unique insights into relationships between fitness, sociality and health.

  12. Human dignity in the Nazi era: implications for contemporary bioethics

    Directory of Open Access Journals (Sweden)

    O'Mathúna Dónal P

    2006-03-01

    Full Text Available Abstract Background The justification for Nazi programs involving involuntary euthanasia, forced sterilisation, eugenics and human experimentation were strongly influenced by views about human dignity. The historical development of these views should be examined today because discussions of human worth and value are integral to medical ethics and bioethics. We should learn lessons from how human dignity came to be so distorted to avoid repetition of similar distortions. Discussion Social Darwinism was foremost amongst the philosophies impacting views of human dignity in the decades leading up to Nazi power in Germany. Charles Darwin's evolutionary theory was quickly applied to human beings and social structure. The term 'survival of the fittest' was coined and seen to be applicable to humans. Belief in the inherent dignity of all humans was rejected by social Darwinists. Influential authors of the day proclaimed that an individual's worth and value were to be determined functionally and materialistically. The popularity of such views ideologically prepared German doctors and nurses to accept Nazi social policies promoting survival of only the fittest humans. A historical survey reveals five general presuppositions that strongly impacted medical ethics in the Nazi era. These same five beliefs are being promoted in different ways in contemporary bioethical discourse. Ethical controversies surrounding human embryos revolve around determinations of their moral status. Economic pressures force individuals and societies to examine whether some people's lives are no longer worth living. Human dignity is again being seen as a relative trait found in certain humans, not something inherent. These views strongly impact what is taken to be acceptable within medical ethics. Summary Five beliefs central to social Darwinism will be examined in light of their influence on current discussions in medical ethics and bioethics. Acceptance of these during the Nazi

  13. Prostasomes: Their Characterisation: Implications for Human Reproduction: Prostasomes and Human Reproduction.

    Science.gov (United States)

    Ronquist, Gunnar

    2015-01-01

    The prostate is a principal accessory genital gland that is vital for normal fertility. Epithelial cells lining the prostate acini release in a defined fashion (exocytosis) organellar nanosized structures named prostasomes. They are involved in the protection of sperm cells against immune response in the female reproductive tract by modulating the complement system and by inhibiting monocyte and neutrophil phagocytosis and lymphocyte proliferation. The immunomodulatory function most probably involves small non-coding RNAs present in prostasomes. Prostasomes have also been proposed to regulate the timing of sperm cell capacitation and induction of the acrosome reaction, since they are rich in various transferable bioactive molecules (e.g. receptors and enzymes) that promote the fertilising ability of sperm cells. Antigenicity of sperm cells has been well documented and implicated in involuntary immunological infertility of human couples, and antisperm antibodies (ASA) occur in several body fluids. The propensity of sperm cells to carry attached prostasomes suggests that they are a new category of sperm antigens. Circulating human ASA recognise prostasomes, and among 12 identified prostasomal antigens, prolactin- inducible protein (95 %) and clusterin (85 %) were immunodominant at the expense of the other 10 that were sporadically occurring.

  14. Human Genome Diversity Project. Summary of planning workshop 3(B): Ethical and human-rights implications

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    The third planning workshop of the Human Genome Diversity Project was held on the campus of the US National Institutes of Health in Bethesda, Maryland, from February 16 through February 18, 1993. The second day of the workshop was devoted to an exploration of the ethical and human-rights implications of the Project. This open meeting centered on three roundtables, involving 12 invited participants, and the resulting discussions among all those present. Attendees and their affiliations are listed in the attached Appendix A. The discussion was guided by a schedule and list of possible issues, distributed to all present and attached as Appendix B. This is a relatively complete, and thus lengthy, summary of the comments at the meeting. The beginning of the summary sets out as conclusions some issues on which there appeared to be widespread agreement, but those conclusions are not intended to serve as a set of detailed recommendations. The meeting organizer is distributing his recommendations in a separate memorandum; recommendations from others who attended the meeting are welcome and will be distributed by the meeting organizer to the participants and to the Project committee.

  15. The immune landscape of human tumors: Implications for cancer immunotherapy.

    Science.gov (United States)

    Bindea, Gabriela; Mlecnik, Bernhard; Angell, Helen K; Galon, Jérôme

    2014-01-01

    Understanding the spontaneous immune response of cancer patients is critical for the design of efficient anticancer immunotherapies. The power of integrative tumor immunology approaches allowed for a comprehensive view of the immune system evolution in the course of tumor progression and recurrence. We have demonstrated that tumor-infiltrating immune cells are spatiotemporally regulated, a finding that has profound implications for the development of efficient anticancer immunotherapies.

  16. Exploring Writing In The Workplace: Implications For Human Resource Development

    OpenAIRE

    AKDERE, Dr. Mesut; AZEVEDO, Dr.Ross E.

    2010-01-01

    Writing in the workplace is among the understudied business topics in the field of HRD. Yet, the impacts of writing in today's workplace are significant, and organizations making it a priority benefit from it. Furthermore, writing is related to the issue of workplace literacy which is the umbrella term for basic communication skills. This literature review provides a general view on workplace writing and discusses implications to HRD within a model research proposal

  17. Therapeutic Role of Rifaximin in Inflammatory Bowel Disease: Clinical Implication of Human Pregnane X Receptor Activation

    OpenAIRE

    Cheng, Jie; Yatrik M. Shah; Ma, Xiaochao; Pang, Xiaoyan; Tanaka, Toshiya; Kodama, Tatsuhiko; Krausz, Kristopher W.; Gonzalez, Frank J.

    2010-01-01

    Human pregnane X receptor (PXR) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a human PXR activator, is in clinical trials for treatment of IBD and has demonstrated efficacy in Crohn's disease and active ulcerative colitis. In the current study, the protective and therapeutic role of rifaximin in IBD and its respective mechanism were investigated. PXR-humanized (hPXR), wild-type, and Pxr-null mice were treated with rifaximin in the dextran sulfate sod...

  18. Human Capital Linkages to Labour Productivity: Implications from Thai Manufacturers

    Science.gov (United States)

    Rukumnuaykit, Pungpond; Pholphirul, Piriya

    2016-01-01

    Human capital investment is a necessary condition for improving labour market outcomes in most countries. Empirical studies to investigate human capital and its linkages on the labour demand side are, however, relatively scarce due to limitations of firm-level data-sets. Using firm-level data from the Thai manufacturing sector, this paper aims to…

  19. Human Capital Linkages to Labour Productivity: Implications from Thai Manufacturers

    Science.gov (United States)

    Rukumnuaykit, Pungpond; Pholphirul, Piriya

    2016-01-01

    Human capital investment is a necessary condition for improving labour market outcomes in most countries. Empirical studies to investigate human capital and its linkages on the labour demand side are, however, relatively scarce due to limitations of firm-level data-sets. Using firm-level data from the Thai manufacturing sector, this paper aims to…

  20. Human genome and the african personality: implications for social work.

    Science.gov (United States)

    Mickel, Elijah; Miller, Sheila D

    2011-01-01

    The integration of the human genome with the African personality should be viewed as an interdependent whole. The African personality, for purposes of this article, comprises Black experiences, Negritude, and an Africa-centered axiology and epistemology. The outcome results in a spiritual focused collective consciousness. Anthropologically, historically (and with the Human Genome Project), genetically Africa has proven to be the source of all human life. Human kind wherever they exist on the planet using the African personality must be viewed as interconnected. Although racism and its progeny discrimination preexist the human genome project (HGP), the human genome provides an evidence-based rationale for the end to all policy and subsequent practice based on race and racism. Policy must be based on evidence to be competent practice. It would be remiss if not irresponsible of social work and the other behavioral scientist concerned with intervention and prevention behaviors to not infuse the findings of the HCPs. The African personality is a concept that provides a wholistic way to evaluate human behavior from an African worldview.

  1. Cardiovascular implications from untreated human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Lundgren, Jens D

    2011-01-01

    Atherosclerotic cardiovascular disease (CVD) has become an important cause of morbidity and mortality among individuals with human immunodeficiency virus (HIV) infection with access to antiretroviral medications, as the risk for AIDS has fallen and life expectancy improved. Traditional CVD risk...

  2. Sex differences in brain organization: implications for human communication.

    Science.gov (United States)

    Hanske-Petitpierre, V; Chen, A C

    1985-12-01

    This article reviews current knowledge in two major research domains: sex differences in neuropsychophysiology, and in human communication. An attempt was made to integrate knowledge from several areas of brain research with human communication and to clarify how such a cooperative effort may be beneficial to both fields of study. By combining findings from the area of brain research, a communication paradigm was developed which contends that brain-related sex differences may reside largely in the area of communication of emotion.

  3. Sixteen years of change in the global terrestrial human footprint and implications for biodiversity conservation

    Science.gov (United States)

    Venter, Oscar; Sanderson, Eric W.; Magrach, Ainhoa; Allan, James R.; Beher, Jutta; Jones, Kendall R.; Possingham, Hugh P.; Laurance, William F.; Wood, Peter; Fekete, Balázs M.; Levy, Marc A.; Watson, James E. M.

    2016-01-01

    Human pressures on the environment are changing spatially and temporally, with profound implications for the planet's biodiversity and human economies. Here we use recently available data on infrastructure, land cover and human access into natural areas to construct a globally standardized measure of the cumulative human footprint on the terrestrial environment at 1 km2 resolution from 1993 to 2009. We note that while the human population has increased by 23% and the world economy has grown 153%, the human footprint has increased by just 9%. Still, 75% the planet's land surface is experiencing measurable human pressures. Moreover, pressures are perversely intense, widespread and rapidly intensifying in places with high biodiversity. Encouragingly, we discover decreases in environmental pressures in the wealthiest countries and those with strong control of corruption. Clearly the human footprint on Earth is changing, yet there are still opportunities for conservation gains. PMID:27552116

  4. Sixteen years of change in the global terrestrial human footprint and implications for biodiversity conservation

    Science.gov (United States)

    Venter, Oscar; Sanderson, Eric W.; Magrach, Ainhoa; Allan, James R.; Beher, Jutta; Jones, Kendall R.; Possingham, Hugh P.; Laurance, William F.; Wood, Peter; Fekete, Balázs M.; Levy, Marc A.; Watson, James E. M.

    2016-08-01

    Human pressures on the environment are changing spatially and temporally, with profound implications for the planet's biodiversity and human economies. Here we use recently available data on infrastructure, land cover and human access into natural areas to construct a globally standardized measure of the cumulative human footprint on the terrestrial environment at 1 km2 resolution from 1993 to 2009. We note that while the human population has increased by 23% and the world economy has grown 153%, the human footprint has increased by just 9%. Still, 75% the planet's land surface is experiencing measurable human pressures. Moreover, pressures are perversely intense, widespread and rapidly intensifying in places with high biodiversity. Encouragingly, we discover decreases in environmental pressures in the wealthiest countries and those with strong control of corruption. Clearly the human footprint on Earth is changing, yet there are still opportunities for conservation gains.

  5. CULTURAL DIMENSIONS IN GLOBAL HUMAN RESOURCE MANAGEMENT: IMPLICATIONS FOR NIGERIA

    Directory of Open Access Journals (Sweden)

    John N. N. Ugoani

    2016-09-01

    Full Text Available As enterprise operations continue to be globalized through overseas expansions, joint ventures, mergers and acquisitions as well as strategic relationships and partnerships transnational organizations need to give attention to issues of culture in human resource management practices as a panacea for prosperity. The global organization is competent if only it is able to bridge the gap between management and culture so that personal relationships with other peoples in the organization and society become in harmony. This is critical because cultural relativity and reality in organizations influence operations. The study was designed to explore possible relationships between cultural dimensions and global human resource management. The survey research design was employed and data generated through primary and secondary sources. The participants comprised of 385 respondents from a cross-section of the population in Nigeria. By Chi-Square test, it was found that culture has a significant positive relationship with global human resource management.

  6. Intracellular insulin in human tumors: examples and implications

    Directory of Open Access Journals (Sweden)

    Radulescu Razvan T

    2011-04-01

    Full Text Available Abstract Insulin is one of the major metabolic hormones regulating glucose homeostasis in the organism and a key growth factor for normal and neoplastic cells. Work conducted primarily over the past 3 decades has unravelled the presence of insulin in human breast cancer tissues and, more recently, in human non-small cell lung carcinomas (NSCLC. These findings have suggested that intracellular insulin is involved in the development of these highly prevalent human tumors. A potential mechanism for such involvement is insulin's binding and inactivation of the retinoblastoma tumor suppressor protein (RB which in turn is likely controlled by insulin-degrading enzyme (IDE. This model and its supporting data are collectively covered in this survey in order to provide further insight into insulin-driven oncogenesis and its reversal through future anticancer therapeutics.

  7. Metabolic costs and evolutionary implications of human brain development.

    Science.gov (United States)

    Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas

    2014-09-09

    The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

  8. Asymptomatic brucellosis infection in humans: implications for diagnosis and prevention.

    Science.gov (United States)

    Zhen, Q; Lu, Y; Yuan, X; Qiu, Y; Xu, J; Li, W; Ke, Y; Yu, Y; Huang, L; Wang, Y; Chen, Z

    2013-09-01

    Human brucellosis is mainly caused by contact with Brucella-infected animals and their secretions and carcasses. Individuals who are continuously in contact with animals are considered to be at a high risk but only some show symptoms and are diagnosed as cases of brucellosis. Here, we showed that asymptomatic brucellosis infections occur among humans. Asymptomatic infections mainly result from less frequent contact with Brucella and/or contact with low-virulence Brucella. In our study, patients with asymptomatic infection had low antibody titres and different contact patterns. Awareness of asymptomatic infection is important for early diagnosis of brucellosis and prevention of chronic infection.

  9. Human Rights, Cosmopolitanism and Utopias: Implications for Citizenship Education

    Science.gov (United States)

    Starkey, Hugh

    2012-01-01

    Citizenship education, defined as learning to live together, requires agreement on certain common principles. One central purpose of a state education system is the transmission of common normative standards such as the human rights and fundamental freedoms that underpin liberal democratic societies. The paper identifies the conceptual roots of…

  10. The human microbiome and probiotics: implications for pediatrics.

    Science.gov (United States)

    Versalovic, James

    2013-01-01

    Steady advances in our knowledge of the composition and function of the human microbiome at multiple body sites including the gut, skin and airways will likely contribute to our understanding of mechanisms of probiotic action by beneficial microbes. Microbe:microbe and microbe:human interactions are important considerations as we select probiotics for pediatric patients in the future. Although our knowledge about the composition of the microbiome is progressing rapidly, many gaps exist about the functional capacity and metabolic machinery of the human microbiome. Based on a limited amount of data, probiotics appear capable of altering the composition and function of the microbiome. Probiotics may be part of dietary strategies that combine ways to enhance microbiome function with nutrients that may be converted to active compounds promoting human health. Probiotics have yielded beneficial effects in numerous studies in the context of different diseases in pediatric gastroenterology. These disease states include necrotizing enterocolitis, antibiotic-associated diarrhea and colitis, acute gastroenteritis and irritable bowel syndrome. In the skin and airways, it is unclear if probiotics can affect the function of the microbiome to reduce the impact of diseases such as asthma and atopic dermatitis. An enhanced understanding of the effects of probiotics on the microbiome should facilitate selection of optimal probiotic strains for specific diseases in the future.

  11. Human Ecology and Health Advancement: The Newcastle Experience and Implications.

    Science.gov (United States)

    Graham, Jenny; Honari, Morteza

    1992-01-01

    Argues for the necessity of adopting a human ecological framework for the advancement of health. Focusing on the Australian experience, highlights the difficulties in moving beyond the narrow mold of Western Medical Science to a more holistic, quality of life orientation, and suggests that the role of education at all levels of the community is…

  12. Human Rights, Cosmopolitanism and Utopias: Implications for Citizenship Education

    Science.gov (United States)

    Starkey, Hugh

    2012-01-01

    Citizenship education, defined as learning to live together, requires agreement on certain common principles. One central purpose of a state education system is the transmission of common normative standards such as the human rights and fundamental freedoms that underpin liberal democratic societies. The paper identifies the conceptual roots of…

  13. Educating Lone Wolves: Pedagogical Implications of Human Capital Theory.

    Science.gov (United States)

    Baptiste, Ian

    2001-01-01

    Educational practices based on human capital theory are unlikely to alleviate social inequities because the theory views people as isolated materialists driven by desire for goods and security. It assumes an educational meritocracy in which socioeconomic status is limited only by educational investment, and more educated people are presumed to be…

  14. A catalogue of human secreted proteins and its implications

    Directory of Open Access Journals (Sweden)

    Shivakumar Keerthikumar

    2016-11-01

    Full Text Available Under both normal and pathological conditions, cells secrete variety of proteins through classical and non-classical secretory pathways into the extracellular space. Majority of these proteins represent pathophysiology of the cell from which it is secreted. Recently, though more than 92% of the protein coding genes has been mapped by human proteome map project, but number of those proteins that constitutes secretome of the cell still remains elusive. Secreted proteins or the secretome can be accessible in bodily fluids and hence are considered as potential biomarkers to discriminate between healthy and diseased individuals. In order to facilitate the biomarker discovery and to further aid clinicians and scientists working in these arenas, we have compiled and catalogued secreted proteins from the human proteome using integrated bioinformatics approach. In this study, nearly 14% of the human proteome is likely to be secreted through classical and non-classical secretory pathways. Out of which, ~38% of these secreted proteins were found in extracellular vesicles including exosomes and shedding microvesicles. Among these secreted proteins, 94% were detected in human bodily fluids including blood, plasma, serum, saliva, semen, tear and urine. We anticipate that this high confidence list of secreted proteins could serve as a compendium of candidate biomarkers. In addition, the catalogue may provide functional insights in understanding the molecular mechanisms involved in various physiological and pathophysiological conditions of the cell.

  15. Human Ecology and Health Advancement: The Newcastle Experience and Implications.

    Science.gov (United States)

    Graham, Jenny; Honari, Morteza

    1992-01-01

    Argues for the necessity of adopting a human ecological framework for the advancement of health. Focusing on the Australian experience, highlights the difficulties in moving beyond the narrow mold of Western Medical Science to a more holistic, quality of life orientation, and suggests that the role of education at all levels of the community is…

  16. Development and implication of a human-volcano system model

    Science.gov (United States)

    Bachri, Syamsul; Stötter, Johann; Monreal, Matthias; Sartohadi, Junun

    2014-05-01

    In an attempt to understand the complexity of human-environment systems, models help to define, quantify, describe, or simulate complex interactions. With regards to the human-volcano system, we develop a conceptual model in order to assist analysis of its two basic elements, the physical and the social environment. A field survey of the human environment interaction of two of the most active volcanic areas in Indonesia (Mt. Merapi and Mt. Bromo) and a corresponding literature review from other case studies was carried out. A differentiated understanding of human interaction with hazard potential elements within the human-volcano system is the main focus of the model development. We classified volcanic processes and effects as three pairs of dichotomies: positive or negative impacts, on society or environment in an indirect or direct way. Each volcanically induced process or effect characterized accordingly leads to eight distinct process/effect classes. They are positive direct effects on society (PDS); positive direct effects on natural resources (PDN); positive indirect effects on society (PIS); positive indirect effects on natural resources (PIN); negative direct effects on society (NDS); negative direct effects on natural resources (NDN); negative indirect effects on society (NIS) and lastly negative indirect effects on natural resources (NIN). Such differentiated view of volcanic process/effects bears several advantages. First, whereas volcanic processes have hitherto been viewed as hazards only, it becomes possible now to describe a particular process/effect in a particular context as negative or positive. Secondly, such a categorization makes it possible to account for processes of the human-volcano system that do not have a direct physical expression but are of socio-cultural relevance. Thirdly, the greater degree of differentiation that is made possible when evaluating volcanic processes has significant repercussions on the way volcanic risk must be

  17. Ethical implications of the human-animal bond in the laboratory.

    Science.gov (United States)

    Russow, Lilly-Marlene

    2002-01-01

    This analysis of the moral implications of a human-animal bond in a research setting begins by describing a set of criteria that delineate the human-animal bond in general and form the foundation on which moral issues rest. Questions about if, when, and how such bonds are formed are discussed briefly; the discussion focuses on how the concept of a human-animal bond fits into standard moral theories. The conclusion is that impartial theories such as utilitarianism and deontological theories must be supplemented with an ethics of caring and that the moral duties engendered by the human-animal bond are best identified with such a supplemented theory.

  18. Implication of conjugated linoleic acid (CLA) in human health.

    Science.gov (United States)

    Dilzer, Allison; Park, Yeonhwa

    2012-01-01

    Conjugated linoleic acid (CLA) has drawn significant attention in the last two decades for its variety of biologically beneficial effects. CLA reduces body fat, cardiovascular diseases and cancer, and modulates immune and inflammatory responses as well as improves bone mass. It has been suggested that the overall effects of CLA are the results of interactions between two major isomers, cis-9,trans-11 and trans-10,cis-12. This review will primarily focus on current CLA publications involving humans, which are also summarized in the tables. Along with a number of beneficial effects of CLA, there are safety considerations for CLA supplementation in humans, which include effects on liver functions, milk fat depression, glucose metabolism, and oxidative stresses.

  19. Cadmium levels in Europe: implications for human health.

    Science.gov (United States)

    Pan, Jilang; Plant, Jane A; Voulvoulis, Nikolaos; Oates, Christopher J; Ihlenfeld, Christian

    2010-02-01

    In this study we used the Forum of European Geological Surveys geochemical baseline data to examine the distribution of cadmium (Cd) in Europe, with a particular reference to the international soil and water guideline values. The highest cadmium levels were found to occur in topsoil and to follow closely the distribution of P(2)O(5), suggesting that the contamination was from the use of rock phosphate fertilizer in intensive arable agriculture. In terms of human health impacts, food (up to several hundred microg/day) was found as the only major route of exposure to Cd for the non-smoking general population. It appeared that low levels of chronic exposure to Cd resulted in completely different human health impacts than those high levels that had caused the 'itai-itai' disease. Some correlations were suggested between cadmium levels and the age-adjusted prostate or breast cancer rates distributed in the European countries under study.

  20. Senescence of T Lymphocytes: Implications for Enhancing Human Immunity.

    Science.gov (United States)

    Akbar, Arne N; Henson, Sian M; Lanna, Alessio

    2016-12-01

    As humans live longer, a central concern is to find ways to maintain their health as they age. Immunity declines during ageing, as shown by the increased susceptibility to infection by both previously encountered and new pathogens and by the decreased efficacy of vaccination. It is therefore crucial to understand the mechanisms responsible for this decrease in immunity and to develop new strategies to enhance immune function in older humans. We discuss here how the induction of senescence alters leukocyte, and specifically T cell, function. An emerging concept is that senescence and nutrient sensing-signalling pathways within T cells converge to regulate functional responses, and the manipulation of these pathways may offer new ways to enhance immunity during ageing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Cultural dimensions in global human resource management: implications for Nigeria

    OpenAIRE

    John N. N. Ugoani

    2016-01-01

    As enterprise operations continue to be globalized through overseas expansions, joint ventures, mergers and acquisitions as well as strategic relationships and partnerships transnational organizations need to give attention to issues of culture in human resource management practices as a panacea for prosperity. The global organization is competent if only it is able to bridge the gap between management and culture so that personal relationships with other peoples in the organization and socie...

  2. Choline Transporters in Human Lung Adenocarcinoma: Expression and Functional Implications

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Choline is an essential nutrient for cell survival and proliferation, however, the expression and function of choline transporters have not been well identified in cancer. In this study, we detected the mRNA and protein expression of organic cation transporter OCT3, carnitine/cation transporters OCTN 1 and OCTN2,and choline transporter-like protein CTL1 in human lung adenocarcinoma cell lines A549, H1299 and SPC-A-1.Their expression pattern was further confirmed in 25 human primary adenocarcinoma tissues. The choline uptake in these cell lines was significantly blocked by CTL1 inhibitor, but only partially inhibited by OCT or OCTN inhibitors. The efficacy of these inhibitors on cell proliferation is closely correlated with their abilities to block choline transport. Under the native expression of these transporters, the total choline uptake was notably blocked by specific PI3K/AKT inhibitors. These results describe the expression of choline transporters and their relevant function in cell proliferation of human lung adenocarcinoma, thus providing a potential"choline-starvation" strategy of cancer interference through targeting choline transporters, especially CTL1.

  3. Human genomics and microarrays: implications for the plastic surgeon.

    Science.gov (United States)

    Cole, Jana; Isik, Frank

    2002-09-01

    The Human Genome Project was launched in 1989 in an effort to sequence the entire span of human DNA. Although coding sequences are important in identifying mutations, the static order of DNA does not explain how a cell or organism may respond to normal and abnormal biological processes. By examining the mRNA content of a cell, researchers can determine which genes are being activated in response to a stimulus. Traditional methods in molecular biology generally work on a "one gene: one experiment" basis, which means that the throughput is very limited and the "whole picture" of gene function is hard to obtain. To study each of the 60,000 to 80,000 genes in the human genome under each biological circumstance is not practical. Recently, microarrays (also known as gene or DNA chips) have emerged; these allow for the simultaneous determination of expression for thousands of genes and analysis of genome-wide mRNA expression. The purpose of this article is twofold: first, to provide the clinical plastic surgeon with a working knowledge and understanding of the fields of genomics, microarrays, and bioinformatics and second, to present a case to illustrate how these technologies can be applied in the study of wound healing.

  4. Blaming, praising, and protecting our humanity: the implications of everyday dehumanization for judgments of moral status.

    Science.gov (United States)

    Bastian, Brock; Laham, Simon M; Wilson, Sam; Haslam, Nick; Koval, Peter

    2011-09-01

    Being human implies a particular moral status: having moral value, agency, and responsibility. However, people are not seen as equally human. Across two studies, we examine the consequences that subtle variations in the perceived humanness of actors or groups have for their perceived moral status. Drawing on Haslam's two-dimensional model of humanness and focusing on three ways people may be considered to have moral status - moral patiency (value), agency, or responsibility - we demonstrate that subtly denying humanness to others has implications for whether they are blamed, praised, or considered worthy of moral concern and rehabilitation. Moreover, we show that distinct human characteristics are linked to specific judgments of moral status. This work demonstrates that everyday judgments of moral status are influenced by perceptions of humanness.

  5. Transcriptional networks implicated in human nonalcoholic fatty liver disease.

    Science.gov (United States)

    Ye, Hua; Liu, Wei

    2015-10-01

    The transcriptome of nonalcoholic fatty liver disease (NAFLD) was investigated in several studies. However, the implications of transcriptional networks in progressive NAFLD are not clear and mechanisms inducing transition from nonalcoholic simple fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are still elusive. The aims of this study were to (1) construct networks for progressive NAFLD, (2) identify hub genes and functional modules in these networks and (3) infer potential linkages among hub genes, transcription factors and microRNAs (miRNA) for NAFLD progression. A systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) was utilized to dissect transcriptional profiles in 19 normal, 10 NAFL and 16 NASH patients. Based on this framework, 3 modules related to chromosome organization, proteasomal ubiquitin-dependent protein degradation and immune response were identified in NASH network. Furthermore, 9 modules of co-expressed genes associated with NAFL/NASH transition were found. Further characterization of these modules defined 13 highly connected hub genes in NAFLD progression network. Interestingly, 11 significantly changed miRNAs were predicted to target 10 of the 13 hub genes. Characterization of modules and hub genes that may be regulated by miRNAs could facilitate the identification of candidate genes and pathways responsible for NAFL/NASH transition and lead to a better understanding of NAFLD pathogenesis. The identified modules and hub genes may point to potential targets for therapeutic interventions.

  6. Clinical implications of microRNAs in human glioblastoma

    Directory of Open Access Journals (Sweden)

    Masahiro eMizoguchi

    2013-02-01

    Full Text Available Glioblastoma (GBM is one of the most common and dismal brain tumors in adults. Further elucidation of the molecular pathogenesis of GBM is mandatory to improve the overall survival of patients. A novel small non-coding RNA molecule, microRNA (miRNA, appears to represent one of the most attractive target molecules contributing to the pathogenesis of various types of tumors. Recent global analyses have revealed that several miRNAs are clinically implicated in GBM, with some reports indicating the association of miRNA dysregulation with acquired temozolomide (TMZ resistance. More recent studies have revealed that miRNAs could play a role in cancer stem cell (CSC properties, contributing to treatment resistance. In addition, greater impact might be expected from miRNA-targeted therapies based on tumor-derived exosomes that contain numerous functional miRNAs, which could be transferred between tumor cells and surrounding structures. Tumor-derived miRNAs are now considered to be a novel molecular mechanism promoting the progression of GBM. Establishment of miRNA-targeted therapies based on miRNA dysregulation of CSCs could provide effective therapeutic strategies for TMZ-resistant GBM. Recent progress has revealed that miRNAs are not only putative biological markers for diagnosis, but also one of the most promising targets for GBM treatment. Herein, we summarize the translational aspects of miRNAs in the diagnosis and treatment of GBM.

  7. The Legacy of Lawrence Kohlberg: Implications for Counseling and Human Development.

    Science.gov (United States)

    Hayes, Richard L.

    1994-01-01

    Notes that, despite great contributions by Lawrence Kohlberg to understanding of moral development, counselors are only beginning to appreciate fully implications of his developmental psychology for practice of counseling and human development. Draws on collective body of Kohlberg's work to show how seven assumptions have direct relevance for…

  8. Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.

    Science.gov (United States)

    Rabino, Isaac

    2003-01-01

    Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)

  9. Human Decision Processes: Implications for SSA Support Tools

    Science.gov (United States)

    Picciano, P.

    2013-09-01

    Despite significant advances in computing power and artificial intelligence (AI), few critical decisions are made without a human decision maker in the loop. Space Situational Awareness (SSA) missions are both critical and complex, typically adhering to the human-in-the-loop (HITL) model. The collection of human operators injects a needed diversity of expert knowledge, experience, and authority required to successfully fulfill SSA tasking. A wealth of literature on human decision making exists citing myriad empirical studies and offering a varied set of prescriptive and descriptive models of judgment and decision making (Hastie & Dawes, 2001; Baron, 2000). Many findings have been proven sufficiently robust to allow information architects or system/interface designers to take action to improve decision processes. For the purpose of discussion, these concepts are bifurcated in two groups: 1) vulnerabilities to mitigate, and 2) capabilities to augment. These vulnerabilities and capabilities refer specifically to the decision process and should not be confused with a shortcoming or skill of a specific human operator. Thus the framing of questions and orders, the automated tools with which to collaborate, priming and contextual data, and the delivery of information all play a critical role in human judgment and choice. Evaluating the merits of any decision can be elusive; in order to constrain this discussion, ‘rational choice' will tend toward the economic model characteristics such as maximizing utility and selection consistency (e.g., if A preferred to B, and B preferred to C, than A should be preferred to C). Simple decision models often encourage one to list the pros and cons of a decision, perhaps use a weighting schema, but one way or another weigh the future benefit (or harm) of making a selection. The result (sought by the rationalist models) should drive toward higher utility. Despite notable differences in researchers' theses (to be discussed in the full

  10. Implications of human value shift and persistence for biodiversity conservation.

    Science.gov (United States)

    Manfredo, Michael J; Teel, Tara L; Dietsch, Alia M

    2016-04-01

    Large-scale change in human values and associated behavior change is believed by some to be the ultimate solution to achieve global biodiversity conservation. Yet little is known about the dynamics of values. We contribute to this area of inquiry by examining the trajectory of values affecting views of wildlife in North America. Using data from a 19-state study in the United States and global data from the Schwartz Value Survey, we explored questions of value persistence and change and the nature of attitudinal responses regarding wildlife conservation issues. We found support, based on subjects' ancestry, for the supposition that domination is a prevalent American value orientation toward wildlife that has origins in European Judeo-Christian traditions. Independent of that effect, we also found indications of change. Modernization is contributing to a shift from domination to mutualism value orientations, which is fostering attitudes less centered on human interests and seemingly more consistent with a biocentric philosophy. Our findings suggest that if value shift could be achieved in a purposeful way, then significant and widespread behavior change believed necessary for long-term conservation success may indeed be possible. In particular, greater emphasis on mutualism values may help provide the context for more collaborative approaches to support future conservation efforts. However, given the societal forces at play, it is not at all clear that human-engineered value shift is tenable. Instead of developing strategies aimed at altering values, it may be more productive to create strategies that recognize and work within the boundaries of existing values. Whereas values appear to be in a period of flux, it will be difficult to predict future trends without a better understanding of value formation and shift, particularly under conditions of rapid social-ecological change. © 2016 Society for Conservation Biology.

  11. Can we effectively degrade microcystins? - Implications on human health

    DEFF Research Database (Denmark)

    de la Cruz, Armah A; Antoniou, Maria; Hiskia, Anastasia

    2011-01-01

    in cells resulting in necrosis or apoptosis. Their cyclic structure and novel amino acids enhance their stability and persistence in the environment. Humans are primarily exposed to microcystins via drinking water consumption and accidental ingestion of recreational water. Recreational exposure by skin...... contact or inhalation to microcystins is now recognized to cause a wide range of acute illnesses which can be life-threatening. Microcystins are primarily degraded by microorganisms in the environment, while sunlight can cause the isomerization of the double bonds and hydroxylation in the presence...

  12. Therapeutic implications of microRNAs in human cancer

    OpenAIRE

    Michael Rossbach

    2011-01-01

    MicroRNAs (miRNAs) are a class of highly evolutionarily conserved non-coding RNAs (ncRNAs) that modulate gene expression. Several studies have shown that the expression of miRNAs is deregulated in human malignancies. For ncRNAs and miRNAs, such gene-profiling studies in tumorigenic tissues have identified significant signatures that are of both diagnostic and prognostic value. Addressing the functions of ncRNAs not only give insights into the molecular mechanisms that underlie complex genetic...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    interest on these cells, mainly focused on animal models. Only recently, a few studies have started to address the relevance of the mRGC system in humans and related diseases. We recently discovered that mRGCs resist neurodegeneration in two inherited mitochondrial disorders that cause blindness, i.......e. Leber hereditary optic neuropathy and dominant optic atrophy. The mechanism leading to mRGCs sparing in these blinding disorders, characterized by extensive and selective loss of RGCs, is currently unknown and under investigation. Other studies reported on mRGCs in glaucoma, on genetic variation...

  14. The human genome project: Prospects and implications for clinical medicine

    Energy Technology Data Exchange (ETDEWEB)

    Green, E.D.; Waterston, R.H. (Washington Univ., St. Louis, MO (United States))

    1991-10-09

    The recently initiated human genome project is a large international effort to elucidate the genetic architecture of the genomes of man and several model organisms. The initial phases of this endeavor involve the establishment of rough blueprints (maps) of the genetic landscape of these genomes, with the long-term goal of determining their precise nucleotide sequences and identifying the genes. The knowledge gained by these studies will provide a vital tool for the study of many biologic processes and will have a profound impact on clinical medicine.

  15. Septin 9 promoter region methylation in free circulating DNA-potential role in noninvasive diagnosis of lung cancer: preliminary report.

    Science.gov (United States)

    Powrózek, Tomasz; Krawczyk, Paweł; Kucharczyk, Tomasz; Milanowski, Janusz

    2014-04-01

    Currently, there are no sensitive diagnostic tests that could allow early detection of lung cancer. Among some cancer patients, epigenetic changes in the nature of methylation of different gene promoter regions are observed, which affect expression of suppressor genes such as septin 9 (SEPT9). Due to the ability of detecting these changes in free circulating DNA in peripheral blood, such genes may become ideal markers in early and noninvasive diagnostics of cancer. Methylation of SEPT9 promoter region in plasma DNA is observed frequently in colorectal cancer patients. The aim of the study was to define the frequency of SEPT9 promoter methylation in lung cancer patients and evaluation of usefulness of this marker in early diagnostic of lung cancer. Plasma samples were obtained from 70 untreated patients with different lung cancer pathological diagnosis and disease stage and from 100 healthy individuals. DNA was isolated from peripheral blood plasma and was then subjected to bisulfitation, purification and elution using Abbott mSEPT9 Detection Kit. Methylation level was assessed by real-time PCR with the use of specific SEPT9 promoter methylation probe. Each sample was assayed in the presence of positive and negative control. SEPT9 promoter methylation was detected in 31 (44.3% of the whole studied group) of lung cancer patients finding the result positive when methylation was detected in 1 out of 3 repetitions of each test sample determinations. The marker was present in patients with different pathological diagnosis and disease stage. Analysis of SEPT9 promoter region methylation may be useful in early diagnosis of lung cancer.

  16. Epidemiological and functional implications of molecular variants of human papillomavirus

    Directory of Open Access Journals (Sweden)

    Sichero L.

    2006-01-01

    Full Text Available Human papillomavirus genomes are classified into molecular variants when they present more than 98% of similarity to the prototype sequence within the L1 gene. Comparative nucleotide sequence analyses of these viruses have elucidated some features of their phylogenetic relationship. In addition, human papillomavirus intratype variability has also been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Until the present, little has been published concerning the functional significance of molecular variants. It has been shown that nucleotide variability within the long control region leads to differences in the binding affinity of some cellular transcriptional factors and to the enhancement of the expression of E6 and E7 oncogenes. Furthermore, in vivo and in vitro studies revealed differences in E6 and E7 biochemical and biological properties among molecular variants. Nevertheless, further correlation with additional functional information is needed to evaluate the significance of genome intratypic variability. These results are also important for the development of vaccines and to determine the extent to which immunization with L1 virus-like particles of one variant could induce antibodies that cross-neutralize other variants.

  17. Paleoclimate Implications for Human-Made Climate Change

    CERN Document Server

    Hansen, James E

    2011-01-01

    Milankovic climate oscillations help define climate sensitivity and assess potential human-made climate effects. We conclude that Earth in the warmest interglacial periods was less than 1{\\deg}C warmer than in the Holocene. Goals to limit human-made warming to 2{\\deg}C and CO2 to 450 ppm are not sufficient -- they are prescriptions for disaster. Polar warmth in prior interglacials and the Pliocene does not imply that a significant cushion remains between today's climate and dangerous warming, but rather that Earth today is poised to experience strong amplifying polar feedbacks in response to moderate additional warming. Deglaciation, disintegration of ice sheets, is nonlinear, spurred by amplifying feedbacks. If warming reaches a level that forces deglaciation, the rate of sea level rise will depend on the doubling time for ice sheet mass loss. Satellite gravity data, though too brief to be conclusive, are consistent with a doubling time of 10 years or less, implying the possibility of multi-meter sea level r...

  18. Solar variability and its implications for the human environment

    Energy Technology Data Exchange (ETDEWEB)

    Reid, G.C. [University of Colorado, Boulder, CO (United States). Aeronomy Laboratory

    1999-01-01

    Solar variability can affect human activities in a variety of ways, from changing our climate to disrupting power distribution facilities and shortening the orbital lifetime of satellites. This tutorial paper will be concerned only with effects on the surface environment that can have a direct impact on our everyday life, such as variations in the stratospheric ozone layer that shields us from harmful ultraviolet radiation, and changes in global climate that can hinder or delay the detection of climate changes that might result from our own technological activities. The emphasis is on potential mechanisms, rather than on reported correlations between solar and terrestrial parameters, but reference to certain observations will be made. Realization of a potential impact of solar variability on our local environment has progressed a long way in the last few decades, from denial to partial acceptance, but a complete assessment of its reality and magnitude remains a distant goal. (author)

  19. Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease.

    Science.gov (United States)

    Burdge, Graham C; Lillycrop, Karen A

    2010-08-21

    There is considerable evidence for induction of differential risk of noncommunicable diseases in humans by variation in the quality of the early life environment. Studies in animal models show that induction and stability of induced changes in the phenotype of the offspring involve altered epigenetic regulation by DNA methylation and covalent modifications of histones. These findings indicate that such epigenetic changes are highly gene specific and function at the level of individual CpG dinucleotides. Interventions using supplementation with folic acid or methyl donors during pregnancy, or folic acid after weaning, alter the phenotype and epigenotype induced by maternal dietary constraint during gestation. This suggests a possible means for reducing risk of induced noncommunicable disease, although the design and conduct of such interventions may require caution. The purpose of this review is to discuss recent advances in understanding the mechanism that underlies the early life origins of disease and to place these studies in a broader life-course context.

  20. Commodification of human tissue: implications for feminist and development ethics.

    Science.gov (United States)

    Dickenson, Donna

    2002-05-01

    One effect of late capitalism--the commodification of practically everything--is to knock down the Chinese walls between the natural and productive realms, to use a Marxist framework. Women's labour in egg extraction and 'surrogate' motherhood might then be seen as what it is, labour which produces something of value. But this does not necessarily mean that women will benefit from the commodification of practically everything, in either North or South. In the newly developing biotechnologies involving stem cells, the reverse is more likely, particular given the the shortage in the North of the egg donors who will be increasingly necessary to therapeutic cloning. Although most of the ethical debate has focused on the status of the embryo, this is to define ethics with no reference to global or gender justice. There has been little or no debate about possible exploitation of women, particularly of ovum donors from the South. Countries of the South without national ethics committees or guidelines may be particularly vulnerable: although there is increasing awareness of the susceptibility of poorer countries to abuses in research ethics, very little has been written about how they might be affected by the enormously profitable new technologies exploiting human tissue. Even in the UK, although the new Medical Research Council guidelines make a good deal of the 'gift relationship', what they are actually about is commodification. If donors believe they are demonstrating altruism, but biotechnology firms and researchers use the discourse of commodity and profit, we have not 'incomplete commodification' but complete commodification with a plausibly human face.

  1. Companion animal welfare and possible implications on the human-pet relationship

    OpenAIRE

    2010-01-01

    The role of pets (dogs and cats in particular) in human society has changed in recent years. Nowadays pets are an integral part of the human family and this aspect has many social and emotional implications. For their positive effects on human health, pets are also employed in some special and therapeutic activities known by the generic term of “Pet Therapy”. In these programmes the animal becomes an integral part of the therapeutic plan in order to induce some physical, social, e...

  2. Prognostic implications of Kindlin proteins in human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ning K

    2017-02-01

    Full Text Available Kai Ning,* Haoshaqiang Zhang,* Zhigang Wang, Kun Li Department of Orthopedics Surgery Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: The Kindlin protein family, comprising Kindlin-1, Kindlin-2 and Kindlin-3, play important roles in various human cancers. Here, to explore the clinical significance of Kindlins in human osteosarcomas, quantitative real-time PCR and Western blot analyses were performed to detect the expression of Kindlin-1, Kindlin-2 and Kindlin-3 mRNAs and proteins in 20 self-pairs of osteosarcoma and adjacent noncancerous tissues. Then, immunohistochemistry was performed to examine subcellular localizations and expression patterns of Kindlin proteins in 100 osteosarcoma and matched adjacent noncancerous tissues. Kindlin-1, Kindlin-2 and Kindlin-3 protein immunostainings were localized in the cytoplasm, nucleus and cytoplasm, respectively, of tumor cells in primary osteosarcoma tissues. Statistically, the expression levels of Kindlin-1 and Kindlin-2 mRNAs and proteins in osteosarcoma tissues were all significantly higher (both P<0.01, but those of Kindlin-3 mRNA and protein were both dramatically lower (both P<0.05, than in matched adjacent noncancerous tissues. In addition, the overexpressions of Kindlin-1 and Kindlin-2 proteins were both significantly associated with high tumor grade (both P=0.01, presence of metastasis (both P=0.006, recurrence (both P=0.006 and poor response to chemotherapy (both P=0.02. Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both P=0.01 and disease-free (P=0.02 and 0.01, respectively survivals of osteosarcoma patients. However, no associations were observed between Kindlin-3 expression and various clinicopathologic features and patients’ prognosis. In conclusion, aberrant expression of Kindlin-1 and Kindlin-2 may function

  3. Human resources in science and engineering: Policy implications

    Energy Technology Data Exchange (ETDEWEB)

    Leggon, C.B.

    1995-12-31

    Recently, there has been much debate concerning the adequacy of the United States` (U.S.) human resources base to meet its future needs for science and engineering (S/E) talent. Science policy analysts - and scientists and engineers themselves - disagree about whether there will be any shortages of scientists and engineers, and if so, what they will mean for the U.S. Whether or not these shortages materialize, it is necessary for the U.S. to expand the pool from which it recruits its S/E talent. This paper addresses the question of how to increases the diversity of the S/E talent pool to include those who are projected by the year 2000 to be the majority of entry-level workers in the U.S. workforce: women and racial/ethnic minorities. Market forces alone cannot increase the size and diversity of the U.S. S/E workforce. Policy intervention will continue to be required to increase the diversity of the S/E workforce.

  4. [HPV (Human Papilloma Virus) implication in other cancers than gynaecological].

    Science.gov (United States)

    Badoual, C; Tartour, E; Roussel, H; Bats, A S; Pavie, J; Pernot, S; Weiss, L; Mohamed, A Si; Thariat, J; Hoffmann, C; Péré, H

    2015-08-01

    Worldwide, approximately 5 to 10% of the population is infected by a Human Papilloma Virus (HPV). Some of these viruses, with a high oncogenic risk (HPV HR), are responsible for about 5% of cancer. It is now accepted that almost all carcinomas of the cervix and the vulva are due to an HPV HR (HPV16 and 18) infection. However, these viruses are known to be involved in the carcinogenesis of many other cancers (head and neck [SCCHN], penis, anus). For head and neck cancer, HPV infection is considered as a good prognostic factor. The role of HPV HR in anal cancer is also extensively studied in high-risk patient's population. The role of HPV infection in the carcinogenesis of esophageal, bladder, lung, breast or skin cancers is still debated. Given the multiple possible locations of HPV HR infection, the question of optimizing the management of patients with a HPV+ cancer arises in the implementation of a comprehensive clinical and biological monitoring. It is the same in therapeutics with the existence of a preventive vaccination, for example.

  5. Neuroendocrine alterations in the exercising human: implications for energy homeostasis.

    Science.gov (United States)

    Fuqua, John S; Rogol, Alan D

    2013-07-01

    Complex mechanisms exist in the human to defend against adverse effects of negative energy balance. These include alterations of hormone secretion affecting the growth hormone/insulin-like growth factor system, the adrenal axis, and the reproductive system, particularly in females. Energy deficits are least partially offset by neuroendocrine mechanisms regulating appetite and satiety. The complex feedback mechanisms reporting peripheral fat and energy stores to the central nervous system involve secretion of the peptide hormones leptin and ghrelin, which act centrally on neurons in the arcuate nucleus and anteroventral periventricular area. In addition to appetite regulation, these hormones exert influences on spatially and functionally-related mechanisms regulating reproductive function, such as the kisspeptin-gonadotropin releasing hormone system. Negative energy balance often occurs partially as a result of strenuous and repetitive physical exercise. Exercise stress leads to increased cortisol secretion, but this action is mediated through the induced negative energy balance. In healthy adults with energy deficits, this exercise-induced stress appears to be more important than pure psychological stress in impairing reproductive function. Estrogen deficiency resulting from negative energy balance has important adverse effects on bone density as well as bone microarchitecture, and it may also adversely affect markers of cardiovascular disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Human REM sleep: influence on feeding behaviour, with clinical implications.

    Science.gov (United States)

    Horne, James A

    2015-08-01

    Rapid eye movement (REM) sleep shares many underlying mechanisms with wakefulness, to a much greater extent than does non-REM, especially those relating to feeding behaviours, appetite, curiosity, exploratory (locomotor) activities, as well as aspects of emotions, particularly 'fear extinction'. REM is most evident in infancy, thereafter declining in what seems to be a dispensable manner that largely reciprocates increasing wakefulness. However, human adults retain more REM than do other mammals, where for us it is most abundant during our usual final REM period (fREMP) of the night, nearing wakefulness. The case is made that our REM is unusual, and that (i) fREMP retains this 'dispensability', acting as a proxy for wakefulness, able to be forfeited (without REM rebound) and substituted by physical activity (locomotion) when pressures of wakefulness increase; (ii) REM's atonia (inhibited motor output) may be a proxy for this locomotion; (iii) our nocturnal sleep typically develops into a physiological fast, especially during fREMP, which is also an appetite suppressant; (iv) REM may have 'anti-obesity' properties, and that the loss of fREMP may well enhance appetite and contribute to weight gain ('overeating') in habitually short sleepers; (v) as we also select foods for their hedonic (emotional) values, REM may be integral to developing food preferences and dislikes; and (vii) REM seems to have wider influences in regulating energy balance in terms of exercise 'substitution' and energy (body heat) retention. Avenues for further research are proposed, linking REM with feeding behaviours, including eating disorders, and effects of REM-suppressant medications.

  7. SULFs in human neoplasia: implication as progression and prognosis factors

    Directory of Open Access Journals (Sweden)

    Schved Jean-François

    2011-05-01

    and in renal carcinoma compared to corresponding normal tissues. Furthermore, we found that high SULF1 expression was associated with a poor prognosis in lung adenocarcinoma. Finally, SULF1 and SULF2 were simultaneously overexpressed in 6 cancer types: brain, breast, head and neck, renal, skin and testicular cancers. Conclusions SULF1 and SULF2 are overexpressed in various human cancer types and can be associated to progression and prognosis. Targeting SULF1 and/or SULF2 could be interesting strategies to develop novel cancer therapies.

  8. Were rivers flowing across the Sahara during the last interglacial? Implications for human migration through Africa.

    Science.gov (United States)

    Coulthard, Tom J; Ramirez, Jorge A; Barton, Nick; Rogerson, Mike; Brücher, Tim

    2013-01-01

    Human migration north through Africa is contentious. This paper uses a novel palaeohydrological and hydraulic modelling approach to test the hypothesis that under wetter climates c.100,000 years ago major river systems ran north across the Sahara to the Mediterranean, creating viable migration routes. We confirm that three of these now buried palaeo river systems could have been active at the key time of human migration across the Sahara. Unexpectedly, it is the most western of these three rivers, the Irharhar river, that represents the most likely route for human migration. The Irharhar river flows directly south to north, uniquely linking the mountain areas experiencing monsoon climates at these times to temperate Mediterranean environments where food and resources would have been abundant. The findings have major implications for our understanding of how humans migrated north through Africa, for the first time providing a quantitative perspective on the probabilities that these routes were viable for human habitation at these times.

  9. The molecular machinery regulating apoptosis signal transduction and its implication in human physiology and pathophysiologies.

    Science.gov (United States)

    Hellwig, C T; Passante, E; Rehm, M

    2011-02-01

    The regulation of apoptotic cell death, a terminal and fatal cell fate decision, has been intensely investigated and, due to its paramount implications for human health and disease, has sparked one of the most prolific and competitive research fields in biological and biomedical sciences of the past decades. Many key components of the molecular machinery processing and transducing apoptotic cell death signals have been described in great detail by now, dramatically advancing our understanding of how the network of apoptosis signaling proteins integrates and regulates cell death signals, and ultimately executes apoptosis. Building on the latest significant advances in deciphering apoptosis signal transduction as well as on the central original groundbreaking discoveries in cell death research, we here present an in-depth description of the current knowledge on the core molecular machinery of apoptotic signaling and how it is implicated in human physiology and pathophysiologies.

  10. Policy recommendations and cost implications for a more sustainable framework for European human biomonitoring surveys

    DEFF Research Database (Denmark)

    Joas, Anke; Knudsen, Lisbeth E.; Kolossa-Gehring, Marike

    2015-01-01

    The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of th......, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES....

  11. Cross-cultural Comparison of Learning in Human Hunting : Implications for Life History Evolution.

    Science.gov (United States)

    MacDonald, Katharine

    2007-12-01

    This paper is a cross-cultural examination of the development of hunting skills and the implications for the debate on the role of learning in the evolution of human life history patterns. While life history theory has proven to be a powerful tool for understanding the evolution of the human life course, other schools, such as cultural transmission and social learning theory, also provide theoretical insights. These disparate theories are reviewed, and alternative and exclusive predictions are identified. This study of cross-cultural regularities in how children learn hunting skills, based on the ethnographic literature on traditional hunters, complements existing empirical work and highlights future areas for investigation.

  12. HUMAN CAPITAL THEORY AND HUMAN RESOURCE MANAGEMENT. IMPLICATIONS IN DEVELEOPMENT OF KNOWLEDGE MANAGEMENT STRATEGIES

    Directory of Open Access Journals (Sweden)

    Simona Buta

    2015-02-01

    Full Text Available In terms of the organization, the human capital theory and human resource management raises a number of issues, namely: human capital issues (they relate to attracting, maintaining, developing and rewarding human resources in order to create and maintain a skilled, dedicated and motivated personnel; issues related to the structural capital (with reference to the size and development of organizational structures that stimulate the processes of creating, capturing and sizing of knowledge; issues of organizational capital( those related to knowledge management. Therefore, organizational context, several questions arise: What knowledge do we have? What knowledge do we need now and in the future? How can we create an environment and a culture that encourages individual and organizational learning? How can we do so that both explicit and tacit knowledge to be captured stored and used judiciously? This paper focuses on human capital theory, but there will also be raised concepts associated to the human resources and knowledge management. Therefore, in this paper we try to identify ways in which human resources (HR specialists can support the KM strategy to drive value within organisation, by revising the practices in order to ensure the knowledge focus.

  13. Work-life Balance Decision-making of Norwegian Students: Implications for Human Resources Management

    Directory of Open Access Journals (Sweden)

    Remigiusz Gawlik

    2016-12-01

    Full Text Available Objective: The paper aims at identifying and assessing the significance of work-life balance determinants between the Youth of highly developed societies and its implications for human resources management on the example of Norway. Research Design & Methods: The research target group consists of 236 respondents recruited among Norwegian tertiary education students. It employed literature analysis, two-stage exploratory research: direct individual in-depth interviews, survey based on a self-administered, web-based questionnaire with single-answer, limited choice qualitative & quantitative, as well as explanatory research (informal moderated group discussions. Findings: The research on perceptions of determinants of quality of life and attractiveness of life strategies shows that in a country with relatively high socio-economic development level, such as Norway, differences in rankings do exist. They can be observed in relevance to both material and non-material QoL determinants. Implications & Recommendations: The study revealed a need for deeper research on individually driven early decision-making of future employees and entrepreneurs. This will result in closer modelling of socio-economic phenomena, including more accurate adaptation to trends on the labour market and creation of new business models. Contribution & Value Added: Research value added comes from the comparison of perceptions of quality of life determinants between countries at various stages of socio-economic development and its implications for human resource management.

  14. Implications of global climate change for housing, human settlements and public health.

    Science.gov (United States)

    Hales, Simon; Baker, Michael; Howden-Chapman, Philippa; Menne, Bettina; Woodruff, Rosalie; Woodward, Alistair

    2007-01-01

    Global climate change has profound implications for human societies. The present---ecologically unsustainable--trajectory of human development fails to provide for the basic needs of a substantial fraction of the global population, while diminishing the prospects for future generations. Human-caused climate change has already begun to affect weather patterns, physical and biological phenomena, and vulnerable human communities. Because the social processes of production and consumption have their own momentum, and because carbon dioxide has a long atmospheric lifetime, further climate change is inevitable over the coming century, even allowing for the adoption of mitigation measures. This situation implies that we should also try to reduce, and where possible to prevent, the adverse effects of climate changes by planned adaptation. Will human settlements be able to provide a healthy living environment and shelter from extreme climate events, such as cyclones and heat waves? In this paper, we review the nexus between human health, climate change, and the planning of housing and human settlements. We conclude that adapting to a rapidly changing global environment will be a major challenge, in the context of increasing population and per capita consumption, without increasing pressures on natural systems. Energy-efficient cities and the creation of opportunities for poor countries will be important elements of people centered, ecologically sustainable, development in the twenty-first century.

  15. Endocrine disrupting compounds in drinking water supply system and human health risk implication.

    Science.gov (United States)

    Wee, Sze Yee; Aris, Ahmad Zaharin

    2017-09-01

    To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Human embryonic stem cell research: implications from an ethical and legal standpoint.

    Science.gov (United States)

    Trepagnier, D M

    2000-12-01

    The purpose of this paper is to discuss the ethical and legal implications of one of the newest and most controversial medical breakthroughs. Stem cell research has been performed on mice for many years, but human embryonic stem cells are believed by scientists to be the basis for possible treatments and/or cures to many diseases affecting millions of people around the world. In order to perform research on human embryonic stem cells, numerous ethical issues must be addressed. Guidelines and protocols can be established in order to allow scientists to pursue new medical advances while maintaining the highest ethical standards in the use of human embryos. An alternative to using embryos is adult stem cells which have recently proven to be more versatile than previously believed. Opposing views will always be encountered when facing new science technologies. Where should the ethical line be drawn?

  17. Temporally and spatially partitioned behaviours of spinner dolphins: implications for resilience to human disturbance

    Science.gov (United States)

    Johnston, David W.; Christiansen, Fredrik

    2017-01-01

    Selective forces shape the evolution of wildlife behavioural strategies and influence the spatial and temporal partitioning of behavioural activities to maximize individual fitness. Globally, wildlife is increasingly exposed to human activities which may affect their behavioural activities. The ability of wildlife to compensate for the effects of human activities may have implications for their resilience to disturbance. Resilience theory suggests that behavioural systems which are constrained in their repertoires are less resilient to disturbance than flexible systems. Using behavioural time-series data, we show that spinner dolphins (Stenella longirostris) spatially and temporally partition their behavioural activities on a daily basis. Specifically, spinner dolphins were never observed foraging during daytime, where resting was the predominant activity. Travelling and socializing probabilities were higher in early mornings and late afternoons when dolphins were returning from or preparing for nocturnal feeding trips, respectively. The constrained nature of spinner dolphin behaviours suggests they are less resilient to human disturbance than other cetaceans. These dolphins experience the highest exposure rates to human activities ever reported for any cetaceans. Over the last 30 years human activities have increased significantly in Hawaii, but the spinner dolphins still inhabit these bays. Recent abundance estimates (2011 and 2012) however, are lower than all previous estimates (1979–1981, 1989–1992 and 2003), indicating a possible long-term impact. Quantification of the spatial and temporal partitioning of wildlife behavioural schedules provides critical insight for conservation measures that aim to mitigate the effects of human disturbance. PMID:28280561

  18. Revisiting the origin of modern humans in China and its implications for global human evolution

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The debates over the origin of modern humans have long been centered on two competing theories:the "Out-of-Africa"(single-place origin) theory and the "Multi-regional Evolution" theory.China is an extremely important region where many ancient human fossils were collected along with numerous associated faunal remains and artefacts.These cultural remains,unearthed from different areas in the country and covering a long time span,will help clarify the controversy.The study of cultural materials in China is expected to shed important light on biological evolutionary patterns and social and technical developments of those early humans as well as their environmental conditions.Based on the analysis of Chinese fossils and associated materials,in conjunction with some genetic studies,this paper aims at evaluating each of the two theories in order to stimulate more discussions.Our study suggests that the evolutionary model of "Continuity with Hybridization" is most relevant in reflecting the current understanding of human evolutionary history in China.Furthermore,we propose that the concept of regional diversity of evolutionary models should be seriously considered to illustrate different evolutionary modes applied to different parts of the world.

  19. Are humans prone to autoimmunity? Implications from evolutionary changes in hominin sialic acid biology.

    Science.gov (United States)

    Varki, Ajit

    2017-09-01

    Given varied intrinsic and extrinsic challenges to the immune system, it is unsurprising that each evolutionary lineage evolves distinctive features of immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity. Humans appear prone to many autoimmune diseases, with mechanisms both genetic and environmental. Another rapidly evolving biological system involves sialic acids, a family of monosaccharides that are terminal caps on cell surface and secreted molecules of vertebrates, and play multifarious roles in immunity. We have explored multiple genomic changes in sialic acid biology that occurred in human ancestors (hominins), some with implications for enhanced immunoreactivity, and hence for autoimmunity. Human ancestors lost the enzyme synthesizing the common mammalian sialic acid Neu5Gc, with an accumulation of the precursor sialic acid Neu5Ac. Resulting changes include an enhanced reactivity by some immune cells and increased ability of macrophages to kill bacteria, at the cost of increased endotoxin sensitivity. There are also multiple human-specific evolutionary changes in inhibitory and activating Siglecs, immune cell receptors that recognize sialic acids as "self-associated molecular patterns" (SAMPs) to modulate immunity, but can also be hijacked by pathogen molecular mimicry of SAMPs. Altered expression patterns and fixed or polymorphic SIGLEC pseudogenization in humans has modulated both innate and adaptive immunity, sometimes favoring over-reactivity. Meanwhile, dietary intake of Neu5Gc (derived primarily from red meats) allows metabolic incorporation of this non-human molecule into human cells--apparently the first example of "xeno-autoimmunity" involving "xeno-autoantigen" interactions with circulating "xeno-autoantibodies". Taken together, some of these factors may contribute to the apparent human propensity for autoimmunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Companion animal welfare and possible implications on the human-pet relationship

    Directory of Open Access Journals (Sweden)

    Marina Verga

    2010-01-01

    Full Text Available The role of pets (dogs and cats in particular in human society has changed in recent years. Nowadays pets are an integral part of the human family and this aspect has many social and emotional implications. For their positive effects on human health, pets are also employed in some special and therapeutic activities known by the generic term of “Pet Therapy”. In these programmes the animal becomes an integral part of the therapeutic plan in order to induce some physical, social, emotional, and cognitive improvements in human patients. However, the close bond between companion animals and man is not always the herald of beneficial effects. Sometimes the welfare of pets may be compromised by distress due to many factors, mostly related to the environment and to management by humans. Both behavioural and physiological variables may be analysed in order to evaluate welfare level in pets. Reduced welfare may be indicated by the onset of some behavioural problems, which have usually a multifactorial aetiology, related both to the genetic individual basis and environmental factors. Physiological variables which may be analysed in order to evaluate pet welfare include hormone levels, mainly related to the HPA (hypothalamus-pituitary-adrenal- axis and to the immune systems activations. Behavioural problems may also lead to the relinquishment of pets to shelters. Animals housed in rescue shelters cannot display their ethogram and show behavioural and physiological signs of distress. Thus it is very important to improve the human-pet relationship both by educating owners and reducing the number of stray animals, in accordance with the indications of the European Convention for the Protection of Pet Animals stated at Strasbourg in 1987, mainly as regards pet breeding and welfare. Humans have to realise that adopting pets implies the responsibility to care for their health and welfare, avoiding undue stress in the living environment and improving the

  1. Perspectives on the Present State and Future of Higher Education Faculty Development in Kazakhstan: Implications for National Human Resource Development

    Science.gov (United States)

    Seitova, Dinara

    2016-01-01

    The article aims at examining the present state of higher education faculty development in Kazakhstan in the context of multidimensional nationwide development reforms and exploring implications for the National Human Resource Development of the country. For the purpose of this research, theoretical human resource development (HRD) and…

  2. Exploring the implications of social change for human development: perspectives, issues and future directions.

    Science.gov (United States)

    Chen, Xinyin

    2015-02-01

    Researchers have investigated the implications of social change for human development from different perspectives. The studies published in this special section were conducted within Greenfield's theoretical framework (2009). The findings concerning links between specific sociodemographic features (e.g., commercial activities, schooling) and individual cognition and social behaviour are particularly interesting because they tap the underlying forces that drive human development. To further understand the issues in these studies and in the field, a pluralist-constructive perspective is discussed, which emphasises the integration of diverse values and practices in both Western and non-Western societies and its effects on the development of sophisticated competencies in individual adaptation to the changing global community. In addition, several issues are highlighted and some suggestions are provided for future explorations in this field.

  3. Coping with human errors through system design: Implications for ecological interface design

    DEFF Research Database (Denmark)

    Rasmussen, Jens; Vicente, Kim J.

    1989-01-01

    Research during recent years has revealed that human errors are not stochastic events which can be removed through improved training programs or optimal interface design. Rather, errors tend to reflect either systematic interference between various models, rules, and schemata, or the effects...... of the adaptive mechanisms involved in learning. In terms of design implications, these findings suggest that reliable human-system interaction will be achieved by designing interfaces which tend to minimize the potential for control interference and support recovery from errors. In other words, the focus should...... be on control of the effects of errors rather than on the elimination of errors per se. In this paper, we propose a theoretical framework for interface design that attempts to satisfy these objectives. The goal of our framework, called ecological interface design, is to develop a meaningful representation...

  4. Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research.

    Science.gov (United States)

    Dymond, Simon; Dunsmoor, Joseph E; Vervliet, Bram; Roche, Bryan; Hermans, Dirk

    2015-09-01

    Fear generalization, in which conditioned fear responses generalize or spread to related stimuli, is a defining feature of anxiety disorders. The behavioral consequences of maladaptive fear generalization are that aversive experiences with one stimulus or event may lead one to regard other cues or situations as potential threats that should be avoided, despite variations in physical form. Theoretical and empirical interest in the generalization of conditioned learning dates to the earliest research on classical conditioning in nonhumans. Recently, there has been renewed focus on fear generalization in humans due in part to its explanatory power in characterizing disorders of fear and anxiety. Here, we review existing behavioral and neuroimaging empirical research on the perceptual and non-perceptual (conceptual and symbolic) generalization of fear and avoidance in healthy humans and patients with anxiety disorders. The clinical implications of this research for understanding the etiology and treatment of anxiety is considered and directions for future research described.

  5. Cultural evolution: implications for understanding the human language faculty and its evolution.

    Science.gov (United States)

    Smith, Kenny; Kirby, Simon

    2008-11-12

    Human language is unique among the communication systems of the natural world: it is socially learned and, as a consequence of its recursively compositional structure, offers open-ended communicative potential. The structure of this communication system can be explained as a consequence of the evolution of the human biological capacity for language or the cultural evolution of language itself. We argue, supported by a formal model, that an explanatory account that involves some role for cultural evolution has profound implications for our understanding of the biological evolution of the language faculty: under a number of reasonable scenarios, cultural evolution can shield the language faculty from selection, such that strongly constraining language-specific learning biases are unlikely to evolve. We therefore argue that language is best seen as a consequence of cultural evolution in populations with a weak and/or domain-general language faculty.

  6. Beyond Tsetse--Implications for Research and Control of Human African Trypanosomiasis Epidemics.

    Science.gov (United States)

    Welburn, Susan C; Molyneux, David H; Maudlin, Ian

    2016-03-01

    Epidemics of both forms of human African trypanosomiasis (HAT) are confined to spatially stable foci in Sub-Saharan Africa while tsetse distribution is widespread. Infection rates of Trypanosoma brucei gambiense in tsetse are extremely low and cannot account for the catastrophic epidemics of Gambian HAT (gHAT) seen over the past century. Here we examine the origins of gHAT epidemics and evidence implicating human genetics in HAT epidemiology. We discuss the role of stress causing breakdown of heritable tolerance in silent disease carriers generating gHAT outbreaks and see how peculiarities in the epidemiologies of gHAT and Rhodesian HAT (rHAT) impact on strategies for disease control.

  7. Using Social Robots in Health Settings: Implications of Personalization on Human-Machine Communication

    Directory of Open Access Journals (Sweden)

    Lisa Tam and Rajiv Khosla

    2016-09-01

    Full Text Available In view of the shortage of healthcare workers and a growing aging population, it is worthwhile to explore the applicability of new technologies in improving the quality of healthcare and reducing its cost. However, it remains a challenge to deploy such technologies in environments where individuals have limited knowledge about how to use them. Thus, this paper explores how the social robots designed for use in health settings in Australia have sought to overcome some of the limitations through personalization. Deployed in aged care and home-based care facilities, the social robots are person-centered, emphasizing the personalization of care with human-like attributes (e.g., human appearances to engage in reciprocal communication with users. While there have been debates over the advantages and disadvantages of personalization, this paper discusses the implications of personalization on the design of the robots for enhancing engagement, empowerment and enablement in health settings.

  8. Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application.

    Science.gov (United States)

    Sinha, Sanjay; Iyer, Dharini; Granata, Alessandra

    2014-06-01

    Vascular smooth muscle cells (SMCs) arise from multiple origins during development, raising the possibility that differences in embryological origins between SMCs could contribute to site-specific localization of vascular diseases. In this review, we first examine the developmental pathways and embryological origins of vascular SMCs and then discuss in vitro strategies for deriving SMCs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We then review in detail the potential for vascular disease modeling using iPSC-derived SMCs and consider the pathological implications of heterogeneous embryonic origins. Finally, we touch upon the role of human ESC-derived SMCs in therapeutic revascularization and the challenges remaining before regenerative medicine using ESC- or iPSC-derived cells comes of age.

  9. Variation in macronutrients in human bank milk: influencing factors and implications for human milk banking

    DEFF Research Database (Denmark)

    Michaelsen, K F; Skafte, L; Badsberg, J H;

    1990-01-01

    Protein (P), fat (F), and carbohydrate (C) concentration in expressed human bank milk was determined by infrared analysis of 2,554 samples from 224 mothers. The mean contents of P, F, C, and energy (E, calculated from P, F, and C) were 9.0 g/L, 39.0 g/L, 71.9 g/L, and 696 kcal/L, respectively...... with a high P content, we have developed a "high-protein" milk with a P content of about 12 g/L (true protein) and an E content of about 725 kcal/L. Thus, by continuous monitoring of macronutrient content in human bank milk it is possible to develop a "high-protein" milk with sufficient P and E content....... The main results were as follows: the P and F contents increased slightly with increasing body mass index of the mother, the P content decreased with increasing amounts of milk delivered to the milk bank, and the F content was higher in mothers delivering large amounts of milk. By selecting incoming milk...

  10. Physiological Effects Associated with Quinoa Consumption and Implications for Research Involving Humans: a Review.

    Science.gov (United States)

    Simnadis, Thomas George; Tapsell, Linda C; Beck, Eleanor J

    2015-09-01

    Quinoa is a pseudo-grain consumed as a dietary staple in South America. In recent years, consumer demand for quinoa in the developed world has grown steadily. Its perceived health benefits have been cited as a driving force behind this trend, but there are very few human studies investigating the impact of quinoa consumption. The aim of this review was to identify physiological effects of quinoa consumption with potential for human health. A critical evaluation of animal model studies was conducted. The quality of identified studies was assessed using a methodological quality assessment tool and summative conclusions were drawn to guide the direction of future human research. The majority of studies were of fair quality. Purported physiological effects of quinoa consumption included decreased weight gain, improved lipid profile and improved capacity to respond to oxidative stress. These physiological effects were attributed to the presence of saponins, protein and 20-hydroxyecdysone in the quinoa seed. The implications of these findings are that human studies should investigate the impact of quinoa consumption on weight gain and lipid levels. The role of quinoa as an antioxidant is still unclear and requires further elucidation in animal models.

  11. Human Perceptions Mirror Realities of Carnivore Attack Risk for Livestock: Implications for Mitigating Human-Carnivore Conflict.

    Science.gov (United States)

    Miller, Jennifer R B; Jhala, Yadvendradev V; Schmitz, Oswald J

    2016-01-01

    Human-carnivore conflict is challenging to quantify because it is shaped by both the realities and people's perceptions of carnivore threats. Whether perceptions align with realities can have implications for conflict mitigation: misalignments can lead to heightened and indiscriminant persecution of carnivores whereas alignments can offer deeper insights into human-carnivore interactions. We applied a landscape-scale spatial analysis of livestock killed by tigers and leopards in India to model and map observed attack risk, and surveyed owners of livestock killed by tigers and leopards for their rankings of threats across habitats to map perceived attack risk. Observed tiger risk to livestock was greatest near dense forests and at moderate distances from human activity while leopard risk was greatest near open vegetation. People accurately perceived spatial differences between tiger and leopard hunting patterns, expected greater threat in areas with high values of observed risk for both carnivores. Owners' perception of threats largely did not depend on environmental conditions surrounding their village (spatial location, dominant land-use or observed carnivore risk). Surveys revealed that owners who previously lost livestock to carnivores used more livestock protection methods than those who had no prior losses, and that owners who had recently lost livestock for the first time expressed greater interest in changing their protection methods than those who experienced prior losses. Our findings suggest that in systems where realities and perceptions of carnivore risk align, conservation programs and policies can optimize conservation outcomes by (1) improving the effectiveness of livestock protection methods and (2) working with owners who have recently lost livestock and are most willing to invest effort in adapting protection strategies to mitigate human-carnivore conflict.

  12. Biological Activities of Extracellular Vesicles and Their Cargos from Bovine and Human Milk in Humans and Implications for Infants.

    Science.gov (United States)

    Zempleni, Janos; Aguilar-Lozano, Ana; Sadri, Mahrou; Sukreet, Sonal; Manca, Sonia; Wu, Di; Zhou, Fang; Mutai, Ezra

    2017-01-01

    Extracellular vesicles (EVs) in milk harbor a variety of compounds, including lipids, proteins, noncoding RNAs, and mRNAs. Among the various classes of EVs, exosomes are of particular interest, because cargo sorting in exosomes is a regulated, nonrandom process and exosomes play essential roles in cell-to-cell communication. Encapsulation in exosomes confers protection against enzymatic and nonenzymatic degradation of cargos and provides a pathway for cellular uptake of cargos by endocytosis of exosomes. Compelling evidence suggests that exosomes in bovine milk are transported by intestinal cells, vascular endothelial cells, and macrophages in human and rodent cell cultures, and bovine-milk exosomes are delivered to peripheral tissues in mice. Evidence also suggests that cargos in bovine-milk exosomes, in particular RNAs, are delivered to circulating immune cells in humans. Some microRNAs and mRNAs in bovine-milk exosomes may regulate the expression of human genes and be translated into protein, respectively. Some exosome cargos are quantitatively minor in the diet compared with endogenous synthesis. However, noncanonical pathways have been identified through which low concentrations of dietary microRNAs may alter gene expression, such as the accumulation of exosomes in the immune cell microenvironment and the binding of microRNAs to Toll-like receptors. Phenotypes observed in infant-feeding studies include higher Mental Developmental Index, Psychomotor Development Index, and Preschool Language Scale-3 scores in breastfed infants than in those fed various formulas. In mice, supplementation with plant-derived MIR-2911 improved the antiviral response compared with controls. Porcine-milk exosomes promote the proliferation of intestinal cells in mice. This article discusses the above-mentioned advances in research concerning milk exosomes and their cargos in human nutrition. Implications for infant nutrition are emphasized, where permitted, but data in infants are

  13. Cell and molecular biology of simian virus 40: implications for human infections and disease

    Science.gov (United States)

    Butel, J. S.; Lednicky, J. A.

    1999-01-01

    Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

  14. Therapeutic role of rifaximin in inflammatory bowel disease: clinical implication of human pregnane X receptor activation.

    Science.gov (United States)

    Cheng, Jie; Shah, Yatrik M; Ma, Xiaochao; Pang, Xiaoyan; Tanaka, Toshiya; Kodama, Tatsuhiko; Krausz, Kristopher W; Gonzalez, Frank J

    2010-10-01

    Human pregnane X receptor (PXR) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a human PXR activator, is in clinical trials for treatment of IBD and has demonstrated efficacy in Crohn's disease and active ulcerative colitis. In the current study, the protective and therapeutic role of rifaximin in IBD and its respective mechanism were investigated. PXR-humanized (hPXR), wild-type, and Pxr-null mice were treated with rifaximin in the dextran sulfate sodium (DSS)-induced and trinitrobenzene sulfonic acid (TNBS)-induced IBD models to determine the protective function of human PXR activation in IBD. The therapeutic role of rifaximin was further evaluated in DSS-treated hPXR and Pxr-null mice. Results demonstrated that preadministration of rifaximin ameliorated the clinical hallmarks of colitis in DSS- and TNBS-treated hPXR mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. In addition, higher survival rates and recovery from colitis symptoms were observed in hPXR mice, but not in Pxr-null mice, when rifaximin was administered after the onset of symptoms. Nuclear factor κB (NF-κB) target genes were markedly down-regulated in hPXR mice by rifaximin treatment. In vitro NF-κB reporter assays demonstrated inhibition of NF-κB activity after rifaximin treatment in colon-derived cell lines expressing hPXR. These findings demonstrated the preventive and therapeutic role of rifaximin on IBD through human PXR-mediated inhibition of the NF-κB signaling cascade, thus suggesting that human PXR may be an effective target for the treatment of IBD.

  15. Cell and molecular biology of simian virus 40: implications for human infections and disease

    Science.gov (United States)

    Butel, J. S.; Lednicky, J. A.

    1999-01-01

    Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

  16. Future Implications of Human Embryonic Testing and Modification: Great Medicine or GATTACA?

    Science.gov (United States)

    Brezina, Paul R; Marinelli, Enrico; Bailey, Amelia P

    2016-01-01

    The past several decades have seen tremendous advances in the field of medical genetics. Currently, the application of genetic testing on human embryos determines if embryos harbor a lethal condition or a serious genetic disease. The purpose of this sort of testing is not to "improve" the offspring of a couple. Rather, current testing strategies focus on helping couples to have a healthy family in an efficient manner. Newly emerging technologies have opened the door to test embryos for an exponentially growing number of traits. Additionally, recent reports describe the actual modification of human embryonic DNA. The implications from the application of this technology are many and have the potential to fundamentally change the social paradigm of the human experience. Embryonic testing and modification does have the potential to accomplish good and is not inherently amoral. However, thoughtful consideration should be given by scientists, legislators, and the general population on how to apply this technology in a manner that is both appropriate and equitable and does not result in further social stratification and polarization, both within individual nations and the global community.

  17. Factors implicated in the initiation of human parturition in term and preterm labor: a review.

    Science.gov (United States)

    Ravanos, Konstantinos; Dagklis, Themistoklis; Petousis, Stamatios; Margioula-Siarkou, Chrysoula; Prapas, Yannis; Prapas, Nikolaos

    2015-01-01

    After accommodating the pregnancy for an average of 40 weeks, the uterus expels the fetus, the placenta and the membranes through the birth canal in a process named parturition. The absolute sequence of events that trigger and sustain human parturition are not yet fully clarified. Evidence suggests that spontaneous preterm and term labor seem to share a common inflammatory pathway. However, there are several other factors being involved in the initiation of human parturition. Placental corticotropin releasing hormone production seems to serve as a placental clock that might be set to ring earlier or later determining the duration of pregnancy and timing of labor. Estrogens do not cause contractions but their properties seem to capacitate uterus to coordinate and enhance contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to induce ripening by mediating remodeling of the extracellular matrix and collagen. Infection and microbe invasion resulting in chorioamnionitis also represents a common cause of early preterm labour. This review provides an overview of all these factors considered to be implicated in the initiation of human parturition.

  18. Function and regulation of AUTS2, a gene implicated in autism and human evolution.

    Directory of Open Access Journals (Sweden)

    Nir Oksenberg

    Full Text Available Nucleotide changes in the AUTS2 locus, some of which affect only noncoding regions, are associated with autism and other neurological disorders, including attention deficit hyperactivity disorder, epilepsy, dyslexia, motor delay, language delay, visual impairment, microcephaly, and alcohol consumption. In addition, AUTS2 contains the most significantly accelerated genomic region differentiating humans from Neanderthals, which is primarily composed of noncoding variants. However, the function and regulation of this gene remain largely unknown. To characterize auts2 function, we knocked it down in zebrafish, leading to a smaller head size, neuronal reduction, and decreased mobility. To characterize AUTS2 regulatory elements, we tested sequences for enhancer activity in zebrafish and mice. We identified 23 functional zebrafish enhancers, 10 of which were active in the brain. Our mouse enhancer assays characterized three mouse brain enhancers that overlap an ASD-associated deletion and four mouse enhancers that reside in regions implicated in human evolution, two of which are active in the brain. Combined, our results show that AUTS2 is important for neurodevelopment and expose candidate enhancer sequences in which nucleotide variation could lead to neurological disease and human-specific traits.

  19. Stability of the human polymerase δ holoenzyme and its implications in lagging strand DNA synthesis.

    Science.gov (United States)

    Hedglin, Mark; Pandey, Binod; Benkovic, Stephen J

    2016-03-29

    In eukaryotes, DNA polymerase δ (pol δ) is responsible for replicating the lagging strand template and anchors to the proliferating cell nuclear antigen (PCNA) sliding clamp to form a holoenzyme. The stability of this complex is integral to every aspect of lagging strand replication. Most of our understanding comes from Saccharomyces cerevisae where the extreme stability of the pol δ holoenzyme ensures that every nucleobase within an Okazaki fragment is faithfully duplicated before dissociation but also necessitates an active displacement mechanism for polymerase recycling and exchange. However, the stability of the human pol δ holoenzyme is unknown. We designed unique kinetic assays to analyze the processivity and stability of the pol δ holoenzyme. Surprisingly, the results indicate that human pol δ maintains a loose association with PCNA while replicating DNA. Such behavior has profound implications on Okazaki fragment synthesis in humans as it limits the processivity of pol δ on undamaged DNA and promotes the rapid dissociation of pol δ from PCNA on stalling at a DNA lesion.

  20. Implications of Oxytocin in Human Linguistic Cognition: From Genome to Phenome

    Science.gov (United States)

    Theofanopoulou, Constantina

    2016-01-01

    The neurohormone oxytocin (OXT) has been found to mediate the regulation of complex socioemotional cognition in multiple ways both in humans and other animals. Recent studies have investigated the effects of OXT in different levels of analysis (from genetic to behavioral) chiefly targeting its impact on the social component and only indirectly indicating its implications in other components of our socio-interactive abilities. This article aims at shedding light onto how OXT might be modulating the multimodality that characterizes our higher-order linguistic abilities (vocal-auditory-attentional-memory-social systems). Based on evidence coming from genetic, EEG, fMRI, and behavioral studies, I attempt to establish the promises of this perspective with the goal of stressing the need for neuropeptide treatments to enter clinical practice. PMID:27378840

  1. LIS1 and DCX: Implications for Brain Development and Human Disease in Relation to Microtubules

    Directory of Open Access Journals (Sweden)

    Orly Reiner

    2013-01-01

    Full Text Available Proper lamination of the cerebral cortex requires the orchestrated motility of neurons from their place of birth to their final destination. Improper neuronal migration may result in a wide range of diseases, including brain malformations, such as lissencephaly, mental retardation, schizophrenia, and autism. Ours and other studies have implicated that microtubules and microtubule-associated proteins play an important role in the regulation of neuronal polarization and neuronal migration. Here, we will review normal processes of brain development and neuronal migration, describe neuronal migration diseases, and will focus on the microtubule-associated functions of LIS1 and DCX, which participate in the regulation of neuronal migration and are involved in the human developmental brain disease, lissencephaly.

  2. T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases

    Directory of Open Access Journals (Sweden)

    Al-Qusairi Lama

    2011-07-01

    Full Text Available Abstract In skeletal muscle, the excitation-contraction (EC coupling machinery mediates the translation of the action potential transmitted by the nerve into intracellular calcium release and muscle contraction. EC coupling requires a highly specialized membranous structure, the triad, composed of a central T-tubule surrounded by two terminal cisternae from the sarcoplasmic reticulum. While several proteins located on these structures have been identified, mechanisms governing T-tubule biogenesis and triad formation remain largely unknown. Here, we provide a description of triad structure and plasticity and review the role of proteins that have been linked to T-tubule biogenesis and triad formation and/or maintenance specifically in skeletal muscle: caveolin 3, amphiphysin 2, dysferlin, mitsugumins, junctophilins, myotubularin, ryanodine receptor, and dihydhropyridine Receptor. The importance of these proteins in triad biogenesis and subsequently in muscle contraction is sustained by studies on animal models and by the direct implication of most of these proteins in human myopathies.

  3. The devil we know: the implications of bill C-38 for assisted human reproduction in Canada.

    Science.gov (United States)

    Cattapan, Alana; Cohen, Sara R

    2013-07-01

    In June 2012, the Canadian House of Commons passed the so-called omnibus budget bill, making several important changes to the governance of assisted reproduction in Canada. The bill (Bill C-38) was widely criticized for its unwieldy size and rapid passage through Parliament, preventing adequate parliamentary debate and public scrutiny. Given the substantive nature of the amendments to the Assisted Human Reproduction Act made by Bill C-38, and the lack of relevant discussion about these changes both before and following its passage, this commentary is intended to identify how Bill C-38 may alter the governance of reproductive technologies in Canada. In this commentary, we address some of the more significant changes made by Bill C-38 to the regulation of reproductive medicine in Canada. We identify the benefits and challenges of closing Assisted Human Reproduction Canada, noting that doing so eliminates a much-needed forum for stakeholder consultation in this field. Further, we explore the implications of moving the regulation of donor semen from the Food and Drugs Act to the Assisted Human Reproduction Act; these include increased liability for physicians, and opportunities to expand the existing regulations to account for the needs of lesbian, gay, bisexual, trans, and queer Canadians using donor gametes and recent advances in reproductive technologies. Overall, we argue that although the implementation of a policy framework in this field remains highly dependent on yet-to-be written regulations, the changes to the Assisted Human Reproduction Act enabled by Bill C-38 may significantly alter how Canadians interact with reproductive technologies.

  4. Hormonal regulation of c-KIT receptor and its ligand: implications for human infertility?

    Science.gov (United States)

    Figueira, Marília I; Cardoso, Henrique J; Correia, Sara; Maia, Cláudio J; Socorro, Sílvia

    2014-09-01

    The c-KIT, a tyrosine kinase receptor, and its ligand the stem cell factor (SCF) play an important role in the production of male and female gametes. The interaction of SCF with c-KIT is required for germ cell survival and growth, and abnormalities in the activity of the SCF/c-KIT system have been associated with human infertility. Recently, it was demonstrated that gonadotropic and sex steroid hormones, among others, regulate the expression of SCF and c-KIT in testicular and ovarian cells. Therefore, the hormonal (de)regulation of SCF/c-KIT system in the testis and ovary may be a cause underpinning infertility. In the present review, we will discuss the effects of hormones modulating the expression levels of SCF and c-KIT in the human gonads. In addition, the implications of hormonal regulation of SCF/c-KIT system for germ cell development and fertility will be highlighted. Copyright © 2014. Published by Elsevier GmbH.

  5. Implications of Nitrogen-Climate Interactions for Ambient Air Pollution and Human Health

    Science.gov (United States)

    Haeuber, R.; Peel, J. L.; Garcia, V.; Neas, L.; Russell, A. G.

    2011-12-01

    Nitrogen oxides (NOX) are important components of ambient and indoor air pollution and are emitted from a range of combustion sources, including on-road mobile sources, electric power generators, and non-road mobile sources. While anthropogenic sources dominate, NOX is also formed by lightning and wildland fires and is emitted by soil. Reduced nitrogen (e.g., ammonia, NH3) is also emitted by various sources, including fertilizer application and animal waste decomposition. NOX, ozone and PM2.5 pollution related to atmospheric emissions of nitrogen and other pollutants can cause premature death and a variety of serious health effects. Climate change is expected to impact how nitrogen-related pollutants affect human health. For example, changes in temperature and precipitation patterns are projected to both lengthen the ozone season and intensify high ozone episodes in some areas. Other climate-related changes may increase the atmospheric release of nitrogen compounds through impacts on wildfire regimes, soil emissions, and biogenic emissions from terrestrial ecosystems. This session will examine the potential human health implications of climate change and nitrogen cycle interactions related to ambient air pollution.

  6. Epigenetic regulation of human DCLK-1 gene during colon-carcinogenesis: clinical and mechanistic implications

    Science.gov (United States)

    O’Connell, Malaney; Shubhashish, Sarkar

    2016-01-01

    Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation. The unopposed activation of Wnt/β-catenin pathways, either due to loss of APC function or up-regulation of related stimulatory pathways, results in unopposed hyperproliferation of colonic crypts, considered the single most important risk factor for colon carcinogenesis. Hypermethylation of CpG islands within the promoters of specific genes can potentially inactivate DNA repair genes and/or critical tumor suppressor genes. Recently, CpG methylation of the 5’ promoter of human (h) DCLK1 gene was reported in many human epithelial cancers, including colorectal cancers (CRCs), resulting in the loss of expression of the canonical long isoform of DCLK1 (DCLK1-L) in hCRCs. Instead, a shorter isoform of DCLK1 (DCLK1-S) was discovered to be expressed in hCRCs, from an alternate β promoter of DCLKL1-gene; the clinical and biological implications of these novel findings, in relation to recent publications is discussed. PMID:27777940

  7. Human Health Implications of Waste Dump Cultivated Vegetables in Anyigba, Kogi State, Nigeria

    Directory of Open Access Journals (Sweden)

    Musa, Salihu Danlami

    2013-12-01

    Full Text Available The study is purposely to determine the level of heavy metals in vegetables cultivated on waste dumps and seek its implication on the health of its consumers. Many of these waste dump sites have been converted to agricultural sites particularly for the cultivation of vegetables, to achieve both dietary and economic advantages. Farmers are taking advantage of the positive crop yield effect of these dumpsites. However, there are fears about the possible hazards of the consumption of such crops because of the presence of heavy metals. Amaranthus caudatus vegetables grown on an abandoned dumpsite and an adjacent plot were sampled and subjected to laboratory analysis to determine the levels of heavy metals. The result indicated a slightly higher presence of heavy metals in the adjacent plot, 7.27, 6.53 and 0.72 ppm for Fe, Zn and Cu respectively compared to the abandoned dumpsite where 7.10, 5.37 and 0.58 ppm respectively were recorded for the same elements; the values of the heavy metals were found to be within acceptable limits for human consumption. Although, it has been revealed that consumption of the vegetable may be safe in the short run; constant check must be made on the quality of the crop to avert possible human health hazards as a result of possible build up of the heavy metals due to mineralization.

  8. [Amebiasis: implications of the recognition of Entamoeba dispar and the identification of Entamoeba moshkovskii in humans].

    Science.gov (United States)

    Chacín-Bonilla, Leonor

    2010-06-01

    The history of Entamoeba histolytica is very confuse and shows several wrong concepts about the parasite and its relationship with the host. The poor correlation between the prevalence of asymptomatic and symptomatic amebiasis originated the proposal of three explicative hypothesis, among them was the concept of Brumpt that E. histolytica comprised two morphologically identical species, E. dysenteriae and E. dispar. The application of modern molecular techniques irrefutably proved that E. histolytica was really a complex of two species, confirming the concept of Brumpt almost 7 decades later. Recent studies have identified in humans E. moshkovskii, morphologically indistinguishable from E. histolytica and E. dispar, a great genetic diversity within each of these species, and heterogeneity in virulence among E. histolytica strains. The redescription of E. dispar, and the recovery of E. moshkovskii from humans have had a major impact in our understanding of E. histolytica and amebiasis with important clinical and epidemiologic implications. This has led to the need of a reevaluation of the infection in terms of prevalence and morbidity in the global population and to study the geographic distribution, prevalence, and transmission pattern of E. histolytica strains in order to detect those with epidemiologic relevance and predict the risk of amebic disease in a population.

  9. Prominent Human Health Impacts from Several Marine Microbes: History, Ecology, and Public Health Implications

    Directory of Open Access Journals (Sweden)

    P. K. Bienfang

    2011-01-01

    Full Text Available This paper overviews several examples of important public health impacts by marine microbes and directs readers to the extensive literature germane to these maladies. These examples include three types of dinoflagellates (Gambierdiscus spp., Karenia brevis, and Alexandrium fundyense, BMAA-producing cyanobacteria, and infectious microbes. The dinoflagellates are responsible for ciguatera fish poisoning, neurotoxic shellfish poisoning, and paralytic shellfish poisoning, respectively, that have plagued coastal populations over time. Research interest on the potential for marine cyanobacteria to contribute BMAA into human food supplies has been derived by BMAA's discovery in cycad seeds and subsequent implication as the putative cause of amyotrophic lateral sclerosis/parkinsonism dementia complex among the Chamorro people of Guam. Recent UPLC/MS analyses indicate that recent reports that BMAA is prolifically distributed among marine cyanobacteria at high concentrations may be due to analyte misidentification in the analytical protocols being applied for BMAA. Common infectious microbes (including enterovirus, norovirus, Salmonella, Campylobacter, Shigella, Staphylococcus aureus, Cryptosporidium, and Giardia cause gastrointestinal and skin-related illness. These microbes can be introduced from external human and animal sources, or they can be indigenous to the marine environment.

  10. Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

    Science.gov (United States)

    Swaminathan, Ashwin; Lucas, Robyn M; Harley, David; McMichael, Anthony J

    2014-11-11

    The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations-particularly for children-to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

  11. Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

    Directory of Open Access Journals (Sweden)

    Ashwin Swaminathan

    2014-11-01

    Full Text Available The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations—particularly for children—to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

  12. Implications of global climate change for the assessment and management of human health risks of chemicals in the natural environment.

    Science.gov (United States)

    Balbus, John M; Boxall, Alistair B A; Fenske, Richard A; McKone, Thomas E; Zeise, Lauren

    2013-01-01

    Global climate change (GCC) is likely to alter the degree of human exposure to pollutants and the response of human populations to these exposures, meaning that risks of pollutants could change in the future. The present study, therefore, explores how GCC might affect the different steps in the pathway from a chemical source in the environment through to impacts on human health and evaluates the implications for existing risk-assessment and management practices. In certain parts of the world, GCC is predicted to increase the level of exposure of many environmental pollutants due to direct and indirect effects on the use patterns and transport and fate of chemicals. Changes in human behavior will also affect how humans come into contact with contaminated air, water, and food. Dietary changes, psychosocial stress, and coexposure to stressors such as high temperatures are likely to increase the vulnerability of humans to chemicals. These changes are likely to have significant implications for current practices for chemical assessment. Assumptions used in current exposure-assessment models may no longer apply, and existing monitoring methods may not be robust enough to detect adverse episodic changes in exposures. Organizations responsible for the assessment and management of health risks of chemicals therefore need to be more proactive and consider the implications of GCC for their procedures and processes.

  13. Clinical Implications of Human Population Differences in Genome-wide Rates of Functional Genotypes

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    Ali eTorkamani

    2012-11-01

    Full Text Available There have been a number of recent successes in the use of whole genome sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA sequence variants responsible for individual idiopathic congenital conditions. However, the success of this identification process is heavily influenced by the ancestry or genetic background of a patient with an idiopathic condition. This is so because potential pathogenic variants in a patient’s genome must be contrasted with variants in a reference set of genomes made up of other individuals’ genomes of the same ancestry as the patient. We explored the effect of ignoring the ancestries of both an individual patient and the individuals used to construct reference genomes. We pursued this exploration in two major steps. We first considered variation in the per-genome number and rates likely functional derived (i.e., non-ancestral, based on the chimp genome single nucleotide variants and small indels in 52 individual whole human genomes sampled from 10 different global populations. We took advantage of a suite of computational and bioinformatics techniques to predict the functional effect of over 24 million genomic variants, both coding and non-coding, across these genomes. We found that the typical human genome harbors ~5.5-6.1 million total derived variants, of which ~12,000 are likely to have a functional effect (~5000 coding and ~7000 non-coding. We also found that the rates of functional genotypes per the total number of genotypes in individual whole genomes differ dramatically between human populations. We then created tables showing how the use of comparator or reference genome panels comprised of genomes from individuals that do not have the same ancestral background as a patient can negatively impact pathogenic variant identification. Our results have important implications for clinical sequencing initiatives.

  14. DUF1220-domain copy number implicated in human brain-size pathology and evolution.

    Science.gov (United States)

    Dumas, Laura J; O'Bleness, Majesta S; Davis, Jonathan M; Dickens, C Michael; Anderson, Nathan; Keeney, J G; Jackson, Jay; Sikela, Megan; Raznahan, Armin; Giedd, Jay; Rapoport, Judith; Nagamani, Sandesh S C; Erez, Ayelet; Brunetti-Pierri, Nicola; Sugalski, Rachel; Lupski, James R; Fingerlin, Tasha; Cheung, Sau Wai; Sikela, James M

    2012-09-07

    DUF1220 domains show the largest human-lineage-specific increase in copy number of any protein-coding region in the human genome and map primarily to 1q21, where deletions and reciprocal duplications have been associated with microcephaly and macrocephaly, respectively. Given these findings and the high correlation between DUF1220 copy number and brain size across primate lineages (R(2) = 0.98; p = 1.8 × 10(-6)), DUF1220 sequences represent plausible candidates for underlying 1q21-associated brain-size pathologies. To investigate this possibility, we used specialized bioinformatics tools developed for scoring highly duplicated DUF1220 sequences to implement targeted 1q21 array comparative genomic hybridization on individuals (n = 42) with 1q21-associated microcephaly and macrocephaly. We show that of all the 1q21 genes examined (n = 53), DUF1220 copy number shows the strongest association with brain size among individuals with 1q21-associated microcephaly, particularly with respect to the three evolutionarily conserved DUF1220 clades CON1(p = 0.0079), CON2 (p = 0.0134), and CON3 (p = 0.0116). Interestingly, all 1q21 DUF1220-encoding genes belonging to the NBPF family show significant correlations with frontal-occipital-circumference Z scores in the deletion group. In a similar survey of a nondisease population, we show that DUF1220 copy number exhibits the strongest correlation with brain gray-matter volume (CON1, p = 0.0246; and CON2, p = 0.0334). Notably, only DUF1220 sequences are consistently significant in both disease and nondisease populations. Taken together, these data strongly implicate the loss of DUF1220 copy number in the etiology of 1q21-associated microcephaly and support the view that DUF1220 domains function as general effectors of evolutionary, pathological, and normal variation in brain size. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. On the growth rates of human malignant tumors: implications for medical decision making.

    Science.gov (United States)

    Friberg, S; Mattson, S

    1997-08-01

    Testicular carcinomas, pediatric tumors, and some mesenchymal tumors are examples of rapidly proliferating cell populations, for which the tumor volume doubling time (TVDT) can be counted in days. Cancers from the breast, prostate, and colon are frequently slow-growing, displaying a TVDT of months or years. Irrespective of their growth rates, most human tumors have been found: to start from one single cell, to have a long subclinical period, to grow at constant rates for long periods of time, to start to metastasize often even before the primary is detected, and to have metastases that often grow at approximately the same rate as the primary tumor. The recognition of basic facts in tumor cell kinetics is essential in the evaluation of important present-day strategies in oncology. Among the facts emphasized in this review are: (1) Screening programs. Most tumors are several years old when detectable by present-day diagnostic methods. This makes the term "early detection" questionable. (2) Legal trials. The importance of so-called doctor's delay is often discussed, but the prognostic value of "early" detection is overestimated. (3) Analyses of clinical trials. Such analysis may be differentiated depending on the growth rates of the type of tumor studied. Furthermore, uncritical analysis of survival data may be misleading if the TVDT is not taken into consideration. (4) Analyses of epidemiological data. If causes of malignant tumors in humans are searched for, the time of exposure must be extended far back in the subject's history. (5) Risk estimations by insurance companies. For the majority of human cancers, the 5-year survival rate is not a valid measurement for cure. Thus, basic knowledge of tumor kinetics may have important implications for political health programs, legal trials, medical science, and insurance policies.

  16. Testing the equivalence of modern human cranial covariance structure: Implications for bioarchaeological applications.

    Science.gov (United States)

    von Cramon-Taubadel, Noreen; Schroeder, Lauren

    2016-10-01

    Estimation of the variance-covariance (V/CV) structure of fragmentary bioarchaeological populations requires the use of proxy extant V/CV parameters. However, it is currently unclear whether extant human populations exhibit equivalent V/CV structures. Random skewers (RS) and hierarchical analyses of common principal components (CPC) were applied to a modern human cranial dataset. Cranial V/CV similarity was assessed globally for samples of individual populations (jackknifed method) and for pairwise population sample contrasts. The results were examined in light of potential explanatory factors for covariance difference, such as geographic region, among-group distance, and sample size. RS analyses showed that population samples exhibited highly correlated multivariate responses to selection, and that differences in RS results were primarily a consequence of differences in sample size. The CPC method yielded mixed results, depending upon the statistical criterion used to evaluate the hierarchy. The hypothesis-testing (step-up) approach was deemed problematic due to sensitivity to low statistical power and elevated Type I errors. In contrast, the model-fitting (lowest AIC) approach suggested that V/CV matrices were proportional and/or shared a large number of CPCs. Pairwise population sample CPC results were correlated with cranial distance, suggesting that population history explains some of the variability in V/CV structure among groups. The results indicate that patterns of covariance in human craniometric samples are broadly similar but not identical. These findings have important implications for choosing extant covariance matrices to use as proxy V/CV parameters in evolutionary analyses of past populations. © 2016 Wiley Periodicals, Inc.

  17. The New World of Human Genetics: A dialogue between Practitioners & the General Public on Ethical, Legal & Social Implications of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Schofield, Amy

    2014-12-08

    The history and reasons for launching the Human Genome project and the current uses of genetic human material; Identifying and discussing the major issues stemming directly from genetic research and therapy-including genetic discrimination, medical/ person privacy, allocation of government resources and individual finances, and the effect on the way in which we perceive the value of human life; Discussing the sometimes hidden ethical, social and legislative implications of genetic research and therapy such as informed consent, screening and preservation of genetic materials, efficacy of medical procedures, the role of the government, and equal access to medical coverage.

  18. Acute Meteorite Dust Exposure and Pulmonary Inflammation - Implications for Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness [1-3]" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure [4]. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles [1]. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern [5]. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive [2, 6-9], and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz [6]. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary

  19. Pulmonary Inflammatory Responses To Acute Meteorite Dust Exposures - Implications For Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive, and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative

  20. Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Uzma Shahab

    Full Text Available BACKGROUND: The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP, a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl-4-aminobiphenyl (dG-C8-4ABP in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA. CONCLUSIONS/SIGNIFICANCE: This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.

  1. Urban river restoration: implications on channel sedimentation patterns and associated ecosystem and human health

    Science.gov (United States)

    Gibbs, H.; Gurnell, A.; Heppell, K.; Spencer, K.

    2012-04-01

    the restored as opposed to the unrestored stretch at both sites, and this difference persisted after standardisation to loading/m2 of channel to account for differing channel dimensions. Metal concentrations at the two sites were analysed using sediment quality guidelines to assess the potential impact upon both the aquatic ecosystem (Environment Agency draft freshwater quality guidelines, 2008) and human health (Dutch Intervention Values for human, plant and/or animal life, 2009). Greater exceedances occurred for the ecological rather than the human health guidelines. Cu, Ni, Pb and Zn were of greatest concern in terms of ecological sediment quality at Sutcliffe Park and Pb and Zn at Chinbrook Meadows. At Sutcliffe Park a greater proportion of samples exceeded the Predicted Effects Level (PEL) in the restored as opposed to the unrestored stretch; conversely at Chinbrook Meadows a greater proportion of samples in the unrestored stretch as opposed to the restored stretch exceeded the PEL. In terms of human health, exceedances only occurred for Cu and Zn at Sutcliffe Park, with the greater proportion being in the restored stretch. The results from this research will have implications for the design, management and maintenance of restored urban rivers in terms of fine sediment accumulation assessment, its quality and the associated potential impact upon ecosystem and human health.

  2. The RNA Modification N6-methyladenosine and Its Implications in Human Disease

    Directory of Open Access Journals (Sweden)

    Pedro J. Batista

    2017-06-01

    Full Text Available Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine (m6A, a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase and eraser (RNA demethylase proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.

  3. Morphological and functional implications of sexual dimorphism in the human skeletal thorax.

    Science.gov (United States)

    García-Martínez, Daniel; Torres-Tamayo, Nicole; Torres-Sanchez, Isabel; García-Río, Francisco; Bastir, Markus

    2016-11-01

    The human respiratory apparatus is characterized by sexual dimorphism, the cranial airways of males being larger (both absolutely and relatively) than those of females. These differences have been linked to sex-specific differences in body composition, bioenergetics, and respiratory function. However, whether morpho-functional variation in the thorax is also related to these features is less clear. We apply 3D geometric morphometrics to study these issues and their implications for respiratory function. Four hundred two landmarks and semilandmarks were measured in CT-reconstructions of rib cages from adult healthy subjects (Nmale  = 18; Nfemale  = 24) in maximal inspiration (MI) and maximal expiration (ME). After Procrustes registration, size and shape data were analyzed by mean comparisons and regression analysis. Respiratory function was quantified through functional size, which is defined as the difference of rib cage size between MI and ME. Males showed significantly larger thorax size (p thorax widening and rib orientation were unrelated to allometry, thorax shortening showed a slight allometric signal. Our findings are in line with previous research on sexual dimorphism of the respiratory system. However, we add that thorax shortening observed previously in males is the only feature caused by allometry. The more horizontally oriented ribs and the wider thorax of males may indicate a greater diaphragmatic contribution to rib cage kinematics than in females, and differences in functional size fit with the need for greater oxygen intake in males. © 2016 Wiley Periodicals, Inc.

  4. Chronic disease prevention and management: implications for health human resources in 2020.

    Science.gov (United States)

    Orchard, Margo; Green, Esther; Sullivan, Terrence; Greenberg, Anna; Mai, Verna

    2008-01-01

    Through improved screening, detection, better and more targeted therapies and the uptake of evidence-based treatment guidelines, cancers are becoming chronic diseases. However, this good-news story has implications for human resource planning and resource allocation. Population-based chronic disease management is a necessary approach to deal with the growing burden of chronic disease in Canada. In this model, an interdisciplinary team works with and educates the patient to monitor symptoms, modify behaviours and self-manage the disease between acute episodes. In addition, the community as a whole is more attuned to disease prevention and risk factor management. Trusted, high-quality evidence-based protocols and healthy public policies that have an impact on the entire population are needed to minimize the harmful effects of chronic disease. Assuming we can overcome the challenges in recruitment, training and new role development, enlightened healthcare teams and community members will work together to maintain the population's health and wellness and to reduce the incidence and burden of chronic disease in Ontario.

  5. Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence.

    Science.gov (United States)

    Wang, P-H; Ko, J-L

    2006-01-01

    The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.

  6. Neutron Structure of Human Carbonic Anhydrase II: Implications for Proton Transfer†

    Science.gov (United States)

    Fisher, S. Zoë; Kovalevsky, Andrey Y.; Domsic, John F.; Mustyakimov, Marat; McKenna, Robert; Silverman, David N.; Langan, Paul A.

    2010-01-01

    Human carbonic anhydrase II (HCA II) catalyzes the reversible hydration of carbon dioxide to form bicarbonate and a proton. Despite many high-resolution X-ray crystal structures, mutagenesis, and kinetic data, the structural details of the active site, especially the proton transfer pathway, are unclear. A large HCA II crystal was prepared at pH 9.0 and subjected to vapor H–D exchange to replace labile hydrogens with deuteriums. Neutron diffraction studies were conducted at the Protein Crystallography Station at Los Alamos National Laboratory. The structure to 2.0 Å resolution reveals several interesting active site features: (1) the Zn-bound solvent appearing to be predominantly a D2O molecule, (2) the orientation and hydrogen bonding pattern of solvent molecules in the active site cavity, (3) the side chain of His64 being unprotonated (neutral) and predominantly in an inward conformation pointing toward the zinc, and (4) the phenolic side chain of Tyr7 appearing to be unprotonated. The implications of these details are discussed, and a proposed mechanism for proton transfer is presented. PMID:20025241

  7. Neutron structure of human carbonic anhydrase II: implications for proton transfer.

    Science.gov (United States)

    Fisher, S Zoë; Kovalevsky, Andrey Y; Domsic, John F; Mustyakimov, Marat; McKenna, Robert; Silverman, David N; Langan, Paul A

    2010-01-26

    Human carbonic anhydrase II (HCA II) catalyzes the reversible hydration of carbon dioxide to form bicarbonate and a proton. Despite many high-resolution X-ray crystal structures, mutagenesis, and kinetic data, the structural details of the active site, especially the proton transfer pathway, are unclear. A large HCA II crystal was prepared at pH 9.0 and subjected to vapor H-D exchange to replace labile hydrogens with deuteriums. Neutron diffraction studies were conducted at the Protein Crystallography Station at Los Alamos National Laboratory. The structure to 2.0 A resolution reveals several interesting active site features: (1) the Zn-bound solvent appearing to be predominantly a D(2)O molecule, (2) the orientation and hydrogen bonding pattern of solvent molecules in the active site cavity, (3) the side chain of His64 being unprotonated (neutral) and predominantly in an inward conformation pointing toward the zinc, and (4) the phenolic side chain of Tyr7 appearing to be unprotonated. The implications of these details are discussed, and a proposed mechanism for proton transfer is presented.

  8. Bioethics methods in the ethical, legal, and social implications of the human genome project literature.

    Science.gov (United States)

    Walker, Rebecca L; Morrissey, Clair

    2014-11-01

    While bioethics as a field has concerned itself with methodological issues since the early years, there has been no systematic examination of how ethics is incorporated into research on the Ethical, Legal and Social Implications (ELSI) of the Human Genome Project. Yet ELSI research may bear a particular burden of investigating and substantiating its methods given public funding, an explicitly cross-disciplinary approach, and the perceived significance of adequate responsiveness to advances in genomics. We undertook a qualitative content analysis of a sample of ELSI publications appearing between 2003 and 2008 with the aim of better understanding the methods, aims, and approaches to ethics that ELSI researchers employ. We found that the aims of ethics within ELSI are largely prescriptive and address multiple groups. We also found that the bioethics methods used in the ELSI literature are both diverse between publications and multiple within publications, but are usually not themselves discussed or employed as suggested by bioethics method proponents. Ethics in ELSI is also sometimes undistinguished from related inquiries (such as social, legal, or political investigations).

  9. Switch from cytology-based to human papillomavirus test-based cervical screening: implications for colposcopy.

    Science.gov (United States)

    Porras, Carolina; Wentzensen, Nicolas; Rodríguez, Ana C; Morales, Jorge; Burk, Robert D; Alfaro, Mario; Hutchinson, Martha; Herrero, Rolando; Hildesheim, Allan; Sherman, Mark E; Wacholder, Sholom; Solomon, Diane; Schiffman, Mark

    2012-04-15

    Human papillomavirus (HPV) testing is more sensitive than cytology; some cervical cancer prevention programs will switch from cytology to carcinogenic HPV test-based screening. The objective of our study is to evaluate the clinical implications of a switch to HPV test-based screening on performance and workload of colposcopy. Women in the population-based, 7-year Guanacaste cohort study were screened at enrollment using cytology. We also took another specimen for HPV DNA testing and collected magnified cervical photographic images (cervigrams). A final case diagnosis (≥cervical intraepithelial neoplasia [CIN] grade 3, CIN2, lesions at referral to colposcopy and the sensitivity versus specificity trade-off of the colposcopic impressions would be similar to programs using cytology (≥ atypical squamous cells of unknown significance [ASCUS]) for referral. The major concern with switching from cytology to more sensitive HPV screening is management of the many HPV-positive women, including those with still nonvisible ≥CIN2 lesions. Our data support the need for a nonvisual diagnostic method to guide management and treatment of HPV-positive women. Copyright © 2011 UICC.

  10. Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies.

    Science.gov (United States)

    Bocharov, Eduard V; Lesovoy, Dmitry M; Goncharuk, Sergey A; Goncharuk, Marina V; Hristova, Kalina; Arseniev, Alexander S

    2013-11-05

    Fibroblast growth factor receptor 3 (FGFR3) transduces biochemical signals via lateral dimerization in the plasma membrane, and plays an important role in human development and disease. Eight different pathogenic mutations, implicated in cancers and growth disorders, have been identified in the FGFR3 transmembrane segment. Here, we describe the dimerization of the FGFR3 transmembrane domain in membrane-mimicking DPC/SDS (9/1) micelles. In the solved NMR structure, the two transmembrane helices pack into a symmetric left-handed dimer, with intermolecular stacking interactions occurring in the dimer central region. Some pathogenic mutations fall within the helix-helix interface, whereas others are located within a putative alternative interface. This implies that although the observed dimer structure is important for FGFR3 signaling, the mechanism of FGFR3-mediated transduction across the membrane is complex. We propose an FGFR3 signaling mechanism that is based on the solved structure, available structures of isolated soluble FGFR domains, and published biochemical and biophysical data.

  11. Trial frequency effects in human temporal bisection: implications for theories of timing.

    Science.gov (United States)

    Jozefowiez, Jeremie; Polack, Cody W; Machado, Armando; Miller, Ralph R

    2014-01-01

    To contrast the classic version of the Scalar Expectancy Theory (SET) with the Behavioral Economic Model (BEM), we examined the effects of trial frequency on human temporal judgments. Mathematical analysis showed that, in a temporal bisection task, SET predicts that participants should show almost exclusive preference for the response associated with the most frequent duration, whereas BEM predicts that, even though participants will be biased, they will still display temporal control. Participants learned to emit one response (R[S]) after a 1.0-s stimulus and another (R[L]) after a 1.5-s stimulus. Then the effects of varying the frequencies of the 1.0-s and 1.5-s stimuli were assessed. Results were more consistent with BEM than with SET. Overall, this research illustrates how the impact of non-temporal factors on temporal discrimination may help us to contrast associative models such as BEM with cognitive models such as SET. Deciding between these two classes of models has important implications regarding the relations between associative learning and timing. This article is part of a Special Issue entitled: Associative and Temporal Learning. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Human Laboratory Settings for Assessing Drug Craving; Implications for the Evaluation of Treatment Efficacy

    Directory of Open Access Journals (Sweden)

    Zahra Alam Mehrjerdi

    2011-04-01

    Full Text Available Research on assessing craving in laboratory settings often involves inducing and then measuring craving in subjects. Cue-induced craving is studied in laboratory settings using the cue reactivity paradigm, in which drug-related photos, videos, evocative scripts, olfactory cues, and paraphernalia may induce craving. Cue-induced craving evoked by drug-related stimuli could be associated with relapse and recurrence of drug addiction. In this article, the authors review different methods of assessing craving in laboratory settings and explain how human laboratory settings can bridge the gap between randomized clinical trials (RCTs and animal models on pharmacological treatments for drug dependence. The brief reviewed literature provides strong evidence that laboratory-based studies of craving may improve our understanding of how subjective reports of drug craving are related to objective measures of drug abuse and laboratory settings provide an opportunity to measure the degree to which they co-vary during pharmacological interventions. This issue has important implications inclinical studies.

  13. From 'human being' to 'social subject': "unfreezing" ergonomics and the implications for understanding and intervening health-disease process.

    Science.gov (United States)

    Morales, Karen Lange; García-Acosta, Gabriel

    2012-01-01

    Ergonomics has been successful in increasing productivity and comfort in the work arena. It has also contributed to reducing occupational accidents. Despite this, ergonomics is frequently limited to understanding the health-disease process related to human-technology interactions, as this process is more complex than what can be understood from an ergonomic evaluation. Recognising this limit, this work ontologically and epistemologically contrasts the notions of 'human being' and 'social subject', and concludes that the study object of ergonomics, or human-technology interaction, greatly depends on social aspects that nowadays are not tackled explicitly: route (history), project, structure, agency, motivations and power. It also analyses how participatory ergonomics tacitly includes many of these aspects, including some implications that the change of notion, from 'human being' to 'social subject', brings to the understanding of the health-disease process and the reduction of associated risks during human activities.

  14. Human loci involved in drug biotransformation: worldwide genetic variation, population structure, and pharmacogenetic implications.

    Science.gov (United States)

    Maisano Delser, Pierpaolo; Fuselli, Silvia

    2013-05-01

    Understanding the role of inheritance in individual variation in drug response is the focus of pharmacogenetics (PGx). A key part of this understanding is quantifying the role of genetic ancestry in this phenotypic outcome. To provide insight into the relationship between ethnicity and drug response, this study first infers the global distribution of PGx variation and defines its structure. Second, the study evaluates if geographic population structure stems from all PGx loci in general, or if structure is caused by specific genes. Lastly, we identify the genetic variants contributing the greatest proportion of such structure. Our study describes the global genetic structure of PGx loci across the 52 populations of the Human Genome Diversity Cell-Line Panel, the most inclusive set of human populations freely available for studies on human genetic variation. By analysing genetic variation at 1,001 single nucleotide polymorphisms (SNPs) involved in biotransformation of exogenous substances, we describe the between-populations PGx variation, as well geographical groupings of diversity. In addition, with discriminant analysis of principal component (DAPC), we infer how many and which groups of populations are supported by PGx variation, and identify which SNPs actually contribute to the PGx structure between such groups. Our results show that intergenic, synonymous and non-synonymous SNPs show similar levels of genetic variation across the globe. Conversely, loci coding for Cytochrome P450s (mainly metabolizing exogenous substances) show significantly higher levels of genetic diversity between populations than the other gene categories. Overall, genetic variation at PGx loci correlates with geographic distances between populations, and the apportionment of genetic variation is similar to that observed for the rest of the genome. In other words, the pattern of PGx variation has been mainly shaped by the demographic history of our species, as in the case of most of our

  15. Assessment of the direct and indirect effects of MPP+ and dopamine on the human proteasome: implications for Parkinson's disease aetiology

    OpenAIRE

    Caneda-Ferrón, B; Girolamo, De, A.; Costa, T; Beck, KE; Layfield, R; Billett, EE

    2008-01-01

    Mitochondrial impairment, glutathione depletion and oxidative stress have been implicated in the pathogenesis of Parkinson’s disease (PD), linked recently to proteasomal dysfunction. Our study analysed how these factors influence the various activities of the proteasome in human SH-SY5Y neuroblastoma cells treated with the PD mimetics MPP+ (a complex 1 inhibitor) or dopamine. Treatment with these toxins led to dose- and time-dependent reductions in ATP and glutathione and also chymotrypsin-li...

  16. Circular Dichroism and Fluorescence Spectroscopic Study of RNA-protein Folding Patterns in Human hnRNP A3 and Their Implications in Human Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    E.SüLEYMANO(G)LU

    2004-01-01

    In human cells, the heterogeneous nuclear ribonucleoproteins (hnRNP) are represented by a group of polypeptides, with various molecular properties, comprizing the most abundant constituents of the cell nucleus. Autoantibodies to hnRNPs have been reported in patients suffering from different rheumatic dieseases since 1980s. Experimental evidence indicates that hnRNP complexes undergo substantial structural changes during mRNA formation and export. However, how this contributes to disease development still has to be elucidated. Here some preliminary physicochemical features of RNA-protein folding and stability patterns of newly characterized hnRNP A3 with further functional implications in development of systemic human autoimmune states are reported.

  17. Implications of the new Food and Drug Administration draft guidance on human factors engineering for diabetes device manufacturers.

    Science.gov (United States)

    Wilcox, Stephen B; Drucker, Daniel

    2012-03-01

    This article discusses the implications of the new Food and Drug Administration's draft guidance on human factors and usability engineering for the development of diabetes-related devices. Important considerations include the challenge of identifying users, when the user population is so dramatically broad, and the challenge of identifying use environments when the same can be said for use environments. Another important consideration is that diabetes-related devices, unlike many other medical devices, are used constantly as part of the user's lifestyle--adding complexity to the focus on human factors and ease of use emphasized by the draft guidance.

  18. Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection.

    Science.gov (United States)

    Sharma, Vivek; Mishra, Mamata; Ghosh, Soumya; Tewari, Richa; Basu, Anirban; Seth, Pankaj; Sen, Ellora

    2007-06-15

    The proinflammatory cytokine interleukin-1beta (IL-1beta) contributes to inflammation and neuronal death in CNS injuries and neurodegenerative pathologies, and astrocytes have been implicated as the primary mediators of IL-1beta induced neuronal death. As astrocytes play an important role in supporting the survival and functions of neurons, we investigated the effect of plant flavonoids quercetin and luteolin, with known anti-inflammatory properties in modulating the response of human astrocytes to IL-1beta for therapeutic intervention. Flavonoids significantly decreased the release of reactive oxygen species (ROS) from astrocytes stimulated with IL-1beta. This decrease was accompanied by an increase in expression of superoxide dismutase (SOD-1) and thioredoxin (TRX1)-mediators associated with protection against oxidative stress. Flavonoids not only modulated the expression of astrocytes specific molecules such as glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and ceruloplasmin (CP) both in the presence and absence of IL-1beta but also decreased the elevated levels of proinflammatory cytokine interleukin-6 (IL-6) and chemokines interleukin-8 (IL-8), interferon-inducible protein (IP-10), monocyte-chemoattractant protein-1 (MCP-1), and RANTES from IL-1beta activated astrocytes. Significant decrease in neuronal apoptosis was observed in neurons cultured in conditioned medium obtained from astrocytes treated with a combination of IL-1beta and flavonoids as compared to that treated with IL-1beta alone. Our result suggests that by (i) enhancing the potential of activated astrocytes to detoxify free radical, (ii) reducing the expression of proinflammatory cytokines and chemokines, and (iii) modulating expression of mediators associated with enhanced physiological activity of astrocyte in response to injury, flavonoids confer (iv) protection against IL-1beta induced astrocyte mediated neuronal damage.

  19. A survey of parabens in commercial pharmaceuticals from China and its implications for human exposure.

    Science.gov (United States)

    Ma, Wan-Li; Zhao, Xue; Lin, Zhong-Yang; Mohammed, Mohammed O A; Zhang, Zi-Feng; Liu, Li-Yan; Song, Wei-Wei; Li, Yi-Fan

    2016-10-01

    Parabens are widely used as antimicrobial preservatives during pharmaceutical production. However, little information is available regarding the occurrence of parabens in commercial pharmaceuticals and their implications for human exposure. In this study, six commonly used parabens were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry with 100 commercial pharmaceuticals collected from China. Almost all of the pharmaceutical samples contained at least one kind of parabens with the detection frequency of 97%. The concentrations of Σ6parabens (sum of the six parabens) ranged from below MDL to 1256ng/g, with mean and median values of 94.8 and 119ng/g, respectively. Methyl paraben (MeP), ethyl paraben (EtP) and propyl paraben (PrP) were the predominant compounds. Significant positive correlation was observed between concentrations of MeP and PrP, indicating their co-applications in pharmaceuticals. Levels of Σ6parabens varied in different categories of pharmaceuticals and increased with their shelf lives. Based on the measured concentrations and daily ingestion rates of pharmaceuticals, the estimated daily intake (EDI) of parabens was calculated. The median values of EDIpharmaceutical for male adults, female adults and children were 4.05, 4.75 and 9.73ng/kg-bw/day, respectively, which were three orders of magnitude lower than those from foodstuffs and personal care products (PCPs). It was firstly reported that the total exposure dose was 0.326mg/kg-bw/day via foodstuffs, PCPs, and pharmaceuticals for Chinese female adults.

  20. Amide-type local anesthetics and human mesenchymal stem cells: clinical implications for stem cell therapy.

    Science.gov (United States)

    Dregalla, Ryan C; Lyons, Nicolette F; Reischling, Patrick D; Centeno, Christopher J

    2014-03-01

    In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are gaining attention as a cell source for the repair and regeneration of tissues spanning an array of medical disciplines. In orthopedics, hMSCs are often delivered in a site-specific manner at the area of interest and may require the concurrent application of local anesthetics (LAs). To address the implications of using hMSCs in combination with anesthetics for intra-articular applications, we investigated the effect that clinically relevant doses of amide-type LAs have on the viability of bone marrow-derived hMSCs and began to characterize the mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from three donors were exposed to the amide-type LAs ropivacaine, lidocaine, bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%, and 50% of the stock solution and incubated with each hMSC line for 40 minutes, 120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays were performed. We found that extended treatment with LAs for 24 hours had a significant impact on both hMSC viability and adhesion. In addition, hMSC treatment with three of the four anesthetics resulted in cell death via apoptosis following brief exposures. Ultimately, we concluded that amide-type LAs induce hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical outcomes, following a similar trend that has been established between these particular anesthetics and articular chondrocytes both in vitro and in vivo.

  1. Amide-Type Local Anesthetics and Human Mesenchymal Stem Cells: Clinical Implications for Stem Cell Therapy

    Science.gov (United States)

    Lyons, Nicolette F.; Reischling, Patrick D.; Centeno, Christopher J.

    2014-01-01

    In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are gaining attention as a cell source for the repair and regeneration of tissues spanning an array of medical disciplines. In orthopedics, hMSCs are often delivered in a site-specific manner at the area of interest and may require the concurrent application of local anesthetics (LAs). To address the implications of using hMSCs in combination with anesthetics for intra-articular applications, we investigated the effect that clinically relevant doses of amide-type LAs have on the viability of bone marrow-derived hMSCs and began to characterize the mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from three donors were exposed to the amide-type LAs ropivacaine, lidocaine, bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%, and 50% of the stock solution and incubated with each hMSC line for 40 minutes, 120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays were performed. We found that extended treatment with LAs for 24 hours had a significant impact on both hMSC viability and adhesion. In addition, hMSC treatment with three of the four anesthetics resulted in cell death via apoptosis following brief exposures. Ultimately, we concluded that amide-type LAs induce hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical outcomes, following a similar trend that has been established between these particular anesthetics and articular chondrocytes both in vitro and in vivo. PMID:24436443

  2. The chemokine CXCL12 and its receptor CXCR4 are implicated in human seminoma metastasis.

    Science.gov (United States)

    McIver, S C; Loveland, K L; Roman, S D; Nixon, B; Kitazawa, R; McLaughlin, E A

    2013-05-01

    Seminoma and non-seminoma tumours increasingly occur within the western population. These tumours originate from carcinoma in situ (CIS) cells, which arise from dysfunctional gonocytes. CXCL12 and its receptors, CXCR4 and CXCR7, have been implicated in migration, proliferation and survival of gonocytes and their precursors and progeny, primordial germ cells and spermatogonial stem cells respectively. We previously found evidence that several miRNA molecules predicted to modulate CXCR4 signalling are differentially expressed during the differentiation of gonocytes into spermatogonia in mice. Bioinformatic analysis predicted these miRNA to modulate CXCR4 signalling, leading us to hypothesize that CXCL12-mediated CXCR4 signalling is involved in the disrupted differentiation of gonocytes that underpins CIS formation. Indeed, we detected CXCL12 in Sertoli cells of normal human testis, and relatively high expression in tumour stroma with concomitant weak staining in dispersed tumour cells. In contrast, CXCR4 was expressed in spermatogonial and meiotic germ cells of normal testis and in the majority of tumour cells. Quantitative RT-PCR identified elevated CXCR4 transcript levels in seminoma compared with normal testis and to non-seminoma, potentially reflecting the higher proportion of dysfunctional germ cells within seminomas. In the normal testis, expression of CXCR4 downstream signalling molecules phospho-MEK1/2 and phospho-ERK1/2 correlated with CXCR4/CXCL12 expression. Strikingly, this correlation was absent in seminoma and non-seminoma samples, suggesting that CXCL12 signalling is disrupted. Proliferation rate and cell survival were not altered by CXCL12 in either seminoma (TCam-2) or non-seminoma (833ke) cell lines. However, CXCL12 exposure induced TCam-2 cell invasion though simulated basement membrane, while in contrast, we provide the novel evidence that CXCR4-expressing non-seminoma cell lines 833ke and NTera2/D1 do not invade in response to CXCL12. These

  3. The human resource implications of improving financial risk protection for mothers and newborns in Zimbabwe.

    Science.gov (United States)

    Chirwa, Yotamu; Witter, Sophie; Munjoma, Malvern; Mashange, Wilson; Ensor, Tim; McPake, Barbara; Munyati, Shungu

    2013-05-28

    A paradigm shift in global health policy on user fees has been evident in the last decade with a growing consensus that user fees undermine equitable access to essential health care in many low and middle income countries. Changes to fees have major implications for human resources for health (HRH), though the linkages are rarely explicitly examined. This study aimed to examine the inter-linkages in Zimbabwe in order to generate lessons for HRH and fee policies, with particular respect to reproductive, maternal and newborn health (RMNH). The study used secondary data and small-scale qualitative fieldwork (key informant interview and focus group discussions) at national level and in one district in 2011. The past decades have seen a shift in the burden of payments onto households. Implementation of the complex rules on exemptions is patchy and confused. RMNH services are seen as hard for families to afford, even in the absence of complications. Human resources are constrained in managing current demand and any growth in demand by high external and internal migration, and low remuneration, amongst other factors. We find that nurses and midwives are evenly distributed across the country (at least in the public sector), though doctors are not. This means that for four provinces, there are not enough doctors to provide more complex care, and only three provinces could provide cover in the event of all deliveries taking place in facilities. This analysis suggests that there is a strong case for reducing the financial burden on clients of RMNH services and also a pressing need to improve the terms and conditions of key health staff. Numbers need to grow, and distribution is also a challenge, suggesting the need for differentiated policies in relation to rural areas, especially for doctors and specialists. The management of user fees should also be reviewed, particularly for non-Ministry facilities, which do not retain their revenues, and receive limited investment in

  4. Teachers' Pedagogical Perspectives and Teaching Practices on Human Rights in Cyprus: An Empirical Exploration and Implications for Human Rights Education

    Science.gov (United States)

    Zembylas, Michalinos; Charalambous, Constadina; Charalambous, Panayiota

    2016-01-01

    This paper describes a qualitative study that explored the understandings of human rights, pedagogical perspectives and practices in human rights teaching of three Greek-Cypriot elementary teachers. The study revealed some significant challenges in human rights teaching that seemed to be common for all three participating teachers. First, all of…

  5. Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery

    Directory of Open Access Journals (Sweden)

    Shu-Ting Pan

    2016-06-01

    Full Text Available The human cytochrome P450 (CYP superfamily consisting of 57 functional genes is the most important group of Phase I drug metabolizing enzymes that oxidize a large number of xenobiotics and endogenous compounds, including therapeutic drugs and environmental toxicants. The CYP superfamily has been shown to expand itself through gene duplication, and some of them become pseudogenes due to gene mutations. Orthologs and paralogs are homologous genes resulting from speciation or duplication, respectively. To explore the evolutionary and functional relationships of human CYPs, we conducted this bioinformatic study to identify their corresponding paralogs, homologs, and orthologs. The functional implications and implications in drug discovery and evolutionary biology were then discussed. GeneCards and Ensembl were used to identify the paralogs of human CYPs. We have used a panel of online databases to identify the orthologs of human CYP genes: NCBI, Ensembl Compara, GeneCards, OMA (“Orthologous MAtrix” Browser, PATHER, TreeFam, EggNOG, and Roundup. The results show that each human CYP has various numbers of paralogs and orthologs using GeneCards and Ensembl. For example, the paralogs of CYP2A6 include CYP2A7, 2A13, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 2R1, 2S1, 2U1, and 2W1; CYP11A1 has 6 paralogs including CYP11B1, 11B2, 24A1, 27A1, 27B1, and 27C1; CYP51A1 has only three paralogs: CYP26A1, 26B1, and 26C1; while CYP20A1 has no paralog. The majority of human CYPs are well conserved from plants, amphibians, fishes, or mammals to humans due to their important functions in physiology and xenobiotic disposition. The data from different approaches are also cross-validated and validated when experimental data are available. These findings facilitate our understanding of the evolutionary relationships and functional implications of the human CYP superfamily in drug discovery.

  6. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    Science.gov (United States)

    Lau, Yat Ming; Cheung, Tak Hong; Yeo, Winnie; Mo, Frankie; Yu, Mei Yung; Lee, Kun Min; Ho, Wendy C S; Yeung, Apple C M; Law, Priscilla T Y; Chan, Paul K S

    2015-01-01

    High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%), HPV-18 (21.6%), HPV-52 (11.9%), and HPV-58 (9.3%). Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1%) patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90), whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79). However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  7. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    Directory of Open Access Journals (Sweden)

    Yat Ming Lau

    Full Text Available High-risk human papillomavirus (HPV types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4 years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%, HPV-18 (21.6%, HPV-52 (11.9%, and HPV-58 (9.3%. Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1% patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90, whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79. However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  8. Finding Near-Earth Asteroid (NEA) Destinations for Human Exploration: Implications for Astrobiology

    Science.gov (United States)

    Landis, Rob; Abell, Paul; Barbee, Brent; Johnson, Lindley

    2012-01-01

    The current number of known potential NEA targets for HSF is limited to those objects whose orbital characteristics are similar to that of the Earth. This is due to the projected capabilities of the exploration systems currently under consideration and development at NASA. However, NEAs with such orbital characteristics often have viewing geometries that place them at low solar elongations and thus are difficult to detect from the vicinity of Earth. While ongoing ground-based surveys and data archives maintained by the NEO Program Observation Program Office and the Minor Planet Center (MPC) have provided a solid basis upon which to build, a more complete catalog of the NEO population is required to inform a robust and sustainable HSF exploration program. Since all the present NEO observing assets are currently confined to the vicinity of the Earth, additional effort must be made to provide capabilities for detection of additional HSF targets via assets beyond Earth orbit. A space-based NEO survey telescope located beyond the vicinity of the Earth, has considerable implications for planetary science and astrobiology. Such a telescope will provide foundational knowledge of our Solar System small body population and detect targets of interest for both the HSF and scientific communities. Data from this asset will yield basic characterization data on the NEOs observed (i.e., albedo, size determination, potential for volatiles and organics, etc.) and help down select targets for future HSF missions. Ideally, the most attractive targets from both HSF and astrobiology perspectives are those NEAs that may contain organic and volatile materials, and which could be effectively sampled at a variety of locations and depths. Presented here is an overview of four space-based survey concepts; any one of which after just a few years of operation will discover many highly accessible NEO targets suitable for robotic and human exploration. Such a space-based survey mission will reveal

  9. The Ethical, Legal, and Social Implications Program of the National Human Genome Research Institute: reflections on an ongoing experiment.

    Science.gov (United States)

    McEwen, Jean E; Boyer, Joy T; Sun, Kathie Y; Rothenberg, Karen H; Lockhart, Nicole C; Guyer, Mark S

    2014-01-01

    For more than 20 years, the Ethical, Legal, and Social Implications (ELSI) Program of the National Human Genome Research Institute has supported empirical and conceptual research to anticipate and address the ethical, legal, and social implications of genomics. As a component of the agency that funds much of the underlying science, the program has always been an experiment. The ever-expanding number of issues the program addresses and the relatively low level of commitment on the part of other funding agencies to support such research make setting priorities especially challenging. Program-supported studies have had a significant impact on the conduct of genomics research, the implementation of genomic medicine, and broader public policies. The program's influence is likely to grow as ELSI research, genomics research, and policy development activities become increasingly integrated. Achieving the benefits of increased integration while preserving the autonomy, objectivity, and intellectual independence of ELSI investigators presents ongoing challenges and new opportunities.

  10. Accumulation of Nitrate in Vegetables and Its Possible Implications to Human Health

    Institute of Scientific and Technical Information of China (English)

    DU Shao-ting; ZHANG Yong-song; LIN Xian-yong

    2007-01-01

    In recent times, there are two kinds of completely opposite viewpoints about the impacts of nitrate on human health. To further objectively understand the effects of nitrate on human health, both of harmfulness and possible benefits of nitrate to human body, it is discussed in this review from the aspects of nitrate accumulation in vegetables, the source of nitrate ingested into human body, and the transformation of nitrate in human body, as well as the pathogenesis and physiological functions of nitrate metabolism.

  11. A human phenome-interactome network of protein complexes implicated in genetic disorders

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Karlberg, Erik, Olof, Linnart; Størling, Zenia, Marian

    2007-01-01

    the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type...

  12. Epistemic Contradictions in Counseling Theories: Implications for the Structure of Human Experience and Counseling Practice

    Science.gov (United States)

    Hansen, James T.

    2007-01-01

    Theories of counseling process are founded on a logical contradiction in that they are simultaneously objectivist and constructivist in nature. Because this epistemic tension is present across diverse theories and has persisted throughout the history of counseling theorizing, the author argues that it has implications for the structure of human…

  13. Threshold behaviour in hydrological systems as (human geo-ecosystems: manifestations, controls, implications

    Directory of Open Access Journals (Sweden)

    M. Sivapalan

    2009-07-01

    Full Text Available In this paper we review threshold behaviour in environmental systems, which are often associated with the onset of floods, contamination and erosion events, and other degenerative processes. Key objectives of this review are to a suggest indicators for detecting threshold behavior, b discuss their implications for predictability, c distinguish different forms of threshold behavior and their underlying controls, and d hypothesise on possible reasons for why threshold behaviour might occur. Threshold behaviour involves a fast qualitative change of either a single process or the response of a system. For elementary phenomena this switch occurs when boundary conditions (e.g., energy inputs or system states as expressed by dimensionless quantities (e.g. the Reynolds number exceed threshold values. Mixing, water movement or depletion of thermodynamic gradients becomes much more efficient as a result. Intermittency is a very good indicator for detecting event scale threshold behavior in hydrological systems. Predictability of intermittent processes/system responses is inherently low for combinations of systems states and/or boundary conditions that push the system close to a threshold. Post hoc identification of "cause-effect relations" to explain when the system became critical is inherently difficult because of our limited ability to perform observations under controlled identical experimental conditions. In this review, we distinguish three forms of threshold behavior. The first one is threshold behavior at the process level that is controlled by the interplay of local soil characteristics and states, vegetation and the rainfall forcing. Overland flow formation, particle detachment and preferential flow are examples of this. The second form of threshold behaviour is the response of systems of intermediate complexity – e.g., catchment runoff response and sediment yield – governed by the redistribution of water and sediments in space and time

  14. Complete-proteome mapping of human influenza A adaptive mutations: implications for human transmissibility of zoonotic strains.

    Directory of Open Access Journals (Sweden)

    Olivo Miotto

    Full Text Available BACKGROUND: There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. CONCLUSIONS: Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an

  15. T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.

    Science.gov (United States)

    Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F

    2016-09-01

    TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.

  16. Integrated Human-Robotic Missions to the Moon and Mars: Mission Operations Design Implications

    Science.gov (United States)

    Mishkin, Andrew; Lee, Young; Korth, David; LeBlanc, Troy

    2007-01-01

    For most of the history of space exploration, human and robotic programs have been independent, and have responded to distinct requirements. The NASA Vision for Space Exploration calls for the return of humans to the Moon, and the eventual human exploration of Mars; the complexity of this range of missions will require an unprecedented use of automation and robotics in support of human crews. The challenges of human Mars missions, including roundtrip communications time delays of 6 to 40 minutes, interplanetary transit times of many months, and the need to manage lifecycle costs, will require the evolution of a new mission operations paradigm far less dependent on real-time monitoring and response by an Earthbound operations team. Robotic systems and automation will augment human capability, increase human safety by providing means to perform many tasks without requiring immediate human presence, and enable the transfer of traditional mission control tasks from the ground to crews. Developing and validating the new paradigm and its associated infrastructure may place requirements on operations design for nearer-term lunar missions. The authors, representing both the human and robotic mission operations communities, assess human lunar and Mars mission challenges, and consider how human-robot operations may be integrated to enable efficient joint operations, with the eventual emergence of a unified exploration operations culture.

  17. Chimeras, moral status, and public policy: implications of the abortion debate for public policy on human/nonhuman chimera research.

    Science.gov (United States)

    Streiffer, Robert

    2010-01-01

    Researchers are increasingly interested in creating chimeras by transplanting human embryonic stem cells (hESCs) into animals early in development. One concern is that such research could confer upon an animal the moral status of a normal human adult but then impermissibly fail to accord it the protections it merits in virtue of its enhanced moral status. Understanding the public policy implications of this ethical conclusion, though, is complicated by the fact that claims about moral status cannot play an unfettered role in public policy. Arguments like those employed in the abortion debate for the conclusion that abortion should be legally permissible even if abortion is not morally permissible also support, to a more limited degree, a liberal policy on hESC research involving the creation of chimeras.

  18. The human secretome atlas initiative: implications in health and disease conditions.

    Science.gov (United States)

    Brown, Kristy J; Seol, Haeri; Pillai, Dinesh K; Sankoorikal, Binu-John; Formolo, Catherine A; Mac, Jenny; Edwards, Nathan J; Rose, Mary C; Hathout, Yetrib

    2013-11-01

    Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts toward secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study. This article is part of a Special Issue entitled: An Updated Secretome.

  19. Loss of N-glycolylneuraminic acid in humans: Mechanisms, consequences, and implications for hominid evolution.

    Science.gov (United States)

    Varki, A

    2001-01-01

    The surface of all mammalian cells is covered with a dense and complex array of sugar chains, which are frequently terminated by members of a family of molecules called sialic acids. One particular sialic acid called N-glycolylneuraminic acid (Neu5Gc) is widely expressed on most mammalian tissues, but is not easily detectable on human cells. In fact, it provokes an immune response in adult humans. The human deficiency of Neu5Gc is explained by an inactivating mutation in the gene encoding CMP-N-acetylneuraminic acid hydroxylase, the rate-limiting enzyme in generating Neu5Gc in cells of other mammals. This deficiency also results in an excess of the precursor sialic acid N-acetylneuraminic acid (Neu5Ac) in humans. This mutation appears universal to modern humans, occurred sometime after our last common ancestor with the great apes, and happens to be one of the first known human-great ape genetic differences with an obvious biochemical readout. While the original selection mechanisms and major biological consequences of this human-specific mutation remain uncertain, several interesting clues are currently being pursued. First, there is evidence that the human condition can explain differences in susceptibility or resistance to certain microbial pathogens. Second, the functions of some endogenous receptors for sialic acids in the immune system may be altered by this difference. Third, despite the lack of any obvious alternate pathway for synthesis, Neu5Gc has been reported in human tumors and possibly in human fetal tissues, and traces have even been detected in normal human tissues. One possible explanation is that this represents accumulation of Neu5Gc from dietary sources of animal origin. Finally, a markedly reduced expression of hydroxylase in the brains of other mammals raises the possibility that the human-specific mutation of this enzyme could have played a role in human brain evolution.

  20. A longitudinal study of human milk composition in the second year postpartum: implications for human milk banking.

    Science.gov (United States)

    Perrin, Maryanne T; Fogleman, April D; Newburg, David S; Allen, Jonathan C

    2017-01-01

    While the composition of human milk has been studied extensively in the first year of lactation, there is a paucity of data regarding human milk composition beyond one year postpartum. Policies vary at milk banks around the world regarding how long lactating women are eligible to donate their milk. The primary purpose of this study is to describe longitudinal changes in human milk composition in the second year postpartum to support the development of evidence based guidelines regarding how long lactating women can donate human milk to a milk bank. Nineteen lactating women in North Carolina provided monthly milk samples from 11 months to 17 months postpartum (N = 131), and two non-profit milk banks provided (N = 33) pooled, unpasteurized milk samples from 51 approved donors less than one year postpartum. There was a significant increase (P milk between 11 and 17 months postpartum, while zinc and calcium concentrations declined, and no changes were observed in lactose, fat, iron and potassium. Human milk in the second year postpartum contained significantly higher concentrations of total protein, lactoferrin, lysozyme and Immunoglobulin A, than milk bank samples, and significantly lower concentrations of zinc, calcium, iron and oligosaccharides. Accepting milk bank donations beyond one year postpartum is a potential strategy for increasing the supply of donor milk, but may require mineral fortification.

  1. Zinc, nickel and cadmium in carambolas marketed in Guangzhou and Hong Kong, China: Implication for human health

    Energy Technology Data Exchange (ETDEWEB)

    Li, J.T.; Liao, B.; Lan, C.Y. [School of Life Sciences and State Key Laboratory of Biocontrol, Sun Yat-sen (Zhongshan) University, Guangzhou 510275, Guangdong (China); Qiu, J.W. [Deparment of Biology, Hong Kong Baptist University, Kowloon, Hong Kong (China); Shu, W.S. [School of Life Sciences and State Key Laboratory of Biocontrol, Sun Yat-sen (Zhongshan) University, Guangzhou 510275, Guangdong (China)], E-mail: shuws@mail.sysu.edu.cn

    2007-12-15

    Carambola (Averrhoa carambola L.) is a popular juicy fruit throughout the tropical and subtropical world. This study was designed to quantify the levels of zinc (Zn), nickel (Ni) and cadmium (Cd) in carambolas marketed in southern China, and further to evaluate the potential health risk of human consumption of carambola. Zinc concentrations, ranging from 1.471 to 2.875 mg/kg (on fresh weight basis), were below the maximum permissible concentration for Zn in fruit of China (5 mg/kg). However, Ni concentrations (0.134-0.676 mg/kg) were considerably higher than the related recommendation values. Furthermore, Cd concentrations in 51% of the carambolas purchased from Guangzhou exceeded the maximum permissible concentration for Cd in fruit of China (0.03 mg/kg). Our results implicated that the consumption of 0.385 kg carambola contaminated by Cd per day would cause the tolerable daily intake (TDI) of Cd by the consumer to be exceeded. In addition, the remarkably high Ni concentrations in carambolas should also be of concern. The status of heavy metal contamination of carambola products marketed in the other regions and their implications for human health should be identified urgently by in-depth studies.

  2. Why We Eat What We Eat: Explanations for Human Food Preferences and Implications for Government Regulation

    OpenAIRE

    Torpoco, Edward A.

    1997-01-01

    As this paper will demonstrate, however, understanding the reasons behind human food preferences can make a tremendous difference in the well-being of the world's people. To this end, Part II examines two competing theories for the origins of human food preferences: cultural idealism and cultural materialism. The first approach starts from the premise that human food preferences are fundamentally arbitrary--i.e., that food preferences are the results of irrational cultural prejudices--whereas...

  3. The human secretome atlas initiative: Implications in health and disease conditions

    OpenAIRE

    Brown, Kristy J; Seol, Haeri; Pillai, Dinesh K.; Sankoorikal, Binu-John; Formolo, Catherine A; Mac, Jenny; Edwards, Nathan J.; Mary C Rose; Hathout, Yetrib

    2013-01-01

    Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts towards secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profi...

  4. Comparative expression analysis of the phosphocreatine circuit in extant primates: Implications for human brain evolution.

    Science.gov (United States)

    Pfefferle, Adam D; Warner, Lisa R; Wang, Catrina W; Nielsen, William J; Babbitt, Courtney C; Fedrigo, Olivier; Wray, Gregory A

    2011-02-01

    While the hominid fossil record clearly shows that brain size has rapidly expanded over the last ~2.5 M.yr. the forces driving this change remain unclear. One popular hypothesis proposes that metabolic adaptations in response to dietary shifts supported greater encephalization in humans. An increase in meat consumption distinguishes the human diet from that of other great apes. Creatine, an essential metabolite for energy homeostasis in muscle and brain tissue, is abundant in meat and was likely ingested in higher quantities during human origins. Five phosphocreatine circuit proteins help regulate creatine utilization within energy demanding cells. We compared the expression of all five phosphocreatine circuit genes in cerebral cortex, cerebellum, and skeletal muscle tissue for humans, chimpanzees, and rhesus macaques. Strikingly, SLC6A8 and CKB transcript levels are higher in the human brain, which should increase energy availability and turnover compared to non-human primates. Combined with other well-documented differences between humans and non-human primates, this allocation of energy to the cerebral cortex and cerebellum may be important in supporting the increased metabolic demands of the human brain. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Early Upper Paleolithic in Eastern Europe and Implications for the Dispersal of Modern Humans

    National Research Council Canada - National Science Library

    M. V. Anikovich; A. A. Sinitsyn; John F. Hoffecker; Vance T. Holliday; V. V. Popov; S. N. Lisitsyn; Steven L. Forman; G. M. Levkovskaya; G. A. Pospelova; I. E. Kuz'mina; N. D. Burova; Paul Goldberg; Richard I. Macphail; Biagio Giaccio; N. D. Praslov

    2007-01-01

    Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation--probably representing modern humans--at archaeological sites on the Don River...

  6. Empirical Analysis of Human Capital, Learning Culture, and Knowledge Management as Antecedents to Organizational Performance: Theoretical and Practical Implications for Logistics Readiness Officer Force Development

    Science.gov (United States)

    2014-03-27

    and productivity at both the individual and firm level. Snell and Dean (1992) posited that human resource management ( HRM ) practices constituted...implications in other fields as well. Among the most important of these is human resource management (Barney and Arikan, 2001). The RBV has helped build a...theoretical bridge between the fields of strategy and human resource management (Wright, et al., 2001) and serves as a setting for this research

  7. Integrative Literature Review: Human Capital Planning--A Review of Literature and Implications for Human Resource Development

    Science.gov (United States)

    Zula, Kenneth J.; Chermack, Thomas J.

    2007-01-01

    The shift in the U.S. economy from a manufacturing powerhouse to a service-driven economy has placed a great emphasis on human capital planning within organizations in order to remain competitive in a new global economy. The link between critical business strategy and the successful implementation of strategy has been well documented in the…

  8. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  9. Human genome education model project. Ethical, legal, and social implications of the human genome project: Education of interdisciplinary professionals

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, J.O. [Alliance of Genetic Support Groups, Chevy Chase, MD (United States); Lapham, E.V. [Georgetown Univ., Washington, DC (United States). Child Development Center

    1996-12-31

    This meeting was held June 10, 1996 at Georgetown University. The purpose of this meeting was to provide a multidisciplinary forum for exchange of state-of-the-art information on the human genome education model. Topics of discussion include the following: psychosocial issues; ethical issues for professionals; legislative issues and update; and education issues.

  10. Accountability for the Human Rights Implications of Natural Disasters : A Proposal for Systemic International Oversight

    NARCIS (Netherlands)

    Hesselman, Marlies; Cubie, Dug

    2015-01-01

    The practical and operational challenges of responding to disasters such as earthquakes, tsunamis and hurricanes are well known, so the recent decision by the UN Human Rights Council to commission research on best practices and challenges in the promotion and protection of human rights in

  11. Education, Human Development and Quality of Life: Measurement Issues and Implications for India

    Science.gov (United States)

    Narayana, M. R.

    2009-01-01

    This paper analyses and compares the measurement of indicators and variables in the construction of education index in Human Development Index (HDI) at the global, national and 18 sub-national human development reports in India since 1990. The results show non-comparability of measurement of the education indicators and variables. This implies…

  12. Productive infection of human peripheral blood mononuclear cells by feline immunodeficiency virus: implications for vector development.

    Science.gov (United States)

    Johnston, J; Power, C

    1999-03-01

    Feline immunodeficiency virus (FIV) is a lentivirus causing immune suppression and neurological disease in cats. Like primate lentiviruses, FIV utilizes the chemokine receptor CXCR4 for infection. In addition, FIV gene expression has been demonstrated in immortalized human cell lines. To investigate the extent and mechanism by which FIV infected primary and immortalized human cell lines, we compared the infectivity of two FIV strains, V1CSF and Petaluma, after cell-free infection. FIV genome was detected in infected human peripheral blood mononuclear cells (PBMC) and macrophages at 21 and 14 days postinfection, respectively. Flow cytometry analysis of FIV-infected human PBMC indicated that antibodies to FIV p24 recognized 12% of the cells. Antibodies binding the CCR3 chemokine receptor maximally inhibited infection of human PBMC by both FIV strains compared to antibodies to CXCR4 or CCR5. Reverse transcriptase levels increased in FIV-infected human PBMC, with detection of viral titers of 10(1.3) to 10(2.1) 50% tissue culture infective doses/10(6) cells depending on the FIV strain examined. Cell death in human PBMC infected with either FIV strain was significantly elevated relative to uninfected control cultures. These findings indicate that FIV can productively infect primary human cell lines and that viral strain specificity should be considered in the development of an FIV vector for gene therapy.

  13. Education, Human Development and Quality of Life: Measurement Issues and Implications for India

    Science.gov (United States)

    Narayana, M. R.

    2009-01-01

    This paper analyses and compares the measurement of indicators and variables in the construction of education index in Human Development Index (HDI) at the global, national and 18 sub-national human development reports in India since 1990. The results show non-comparability of measurement of the education indicators and variables. This implies…

  14. Human Resource Management: Managerial Efficacy in Recruiting and Retaining Teachers-- National Implications

    Science.gov (United States)

    Butcher, Jennifer; Kritsonis, William Allan

    2007-01-01

    Human Resource Management is a branch of an organization which recruits and develops personnel to promote the organization's objectives. Human Resource Management involves interviewing applicants, training staff, and employee retention. Compensation, benefits, employee/labor relations, health, safety, and security issues are a few of the aspects…

  15. Emerging issues in urban ecology: implications for research, social justice, human health, and well-being

    Science.gov (United States)

    Viniece Jennings; Myron F. Floyd; Danielle Shanahan; Christopher Coutts; Alex Sinykin

    2017-01-01

    Urbanization affects landscape structure and the overall human condition in numerous ways. Green spaces include vegetated land cover (e.g., urban forests, trees, riparian zones, parks) which play a distinctive role in urban ecology. This article reviews emergent literature on the linkages between urban green spaces, social justice, and human health. We explore this...

  16. Humanity in the Digital Age: Cognitive, Social, Emotional, and Ethical Implications

    Science.gov (United States)

    Yamamoto, Junko; Ananou, Simeon

    2015-01-01

    Even though technology has brought great benefits to current society, there are also indications that the manner in which people use technology has undermined their humanity in some respects. In this article the authors frame human nature in terms of four dimensions: cognition, social interaction, emotion, and ethics. We argue that while basic…

  17. Human-Computer Interaction (HCI) in Educational Environments: Implications of Understanding Computers as Media.

    Science.gov (United States)

    Berg, Gary A.

    2000-01-01

    Reviews literature in the field of human-computer interaction (HCI) as it applies to educational environments. Topics include the origin of HCI; human factors; usability; computer interface design; goals, operations, methods, and selection (GOMS) models; command language versus direct manipulation; hypertext; visual perception; interface…

  18. Implications of Human Pattern Processing for the Design of Artificial Knowledge Systems.

    Science.gov (United States)

    Hayes-Roth, Barbara

    This paper presents evidence that four design principles commonly embodied in artificial knowledge systems are inconsistent with human cognitive capabilities. Because these principles are widely accepted as characteristics of human knowledge processing, common theoretical properties related to cognitive psychology and artificial intelligence which…

  19. Non-human primate regulatory T cells: Current biology and implications for transplantation

    NARCIS (Netherlands)

    E.M. Dons (Eefje); G. Raimondi (Giorgio); D.K.C. Cooper (David); A.W. Thomson (Angus)

    2010-01-01

    textabstractRegulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we discuss the properties of non-human pri

  20. Beat Keeping in a Sea Lion As Coupled Oscillation: Implications for Comparative Understanding of Human Rhythm.

    Science.gov (United States)

    Rouse, Andrew A; Cook, Peter F; Large, Edward W; Reichmuth, Colleen

    2016-01-01

    Human capacity for entraining movement to external rhythms-i.e., beat keeping-is ubiquitous, but its evolutionary history and neural underpinnings remain a mystery. Recent findings of entrainment to simple and complex rhythms in non-human animals pave the way for a novel comparative approach to assess the origins and mechanisms of rhythmic behavior. The most reliable non-human beat keeper to date is a California sea lion, Ronan, who was trained to match head movements to isochronous repeating stimuli and showed spontaneous generalization of this ability to novel tempos and to the complex rhythms of music. Does Ronan's performance rely on the same neural mechanisms as human rhythmic behavior? In the current study, we presented Ronan with simple rhythmic stimuli at novel tempos. On some trials, we introduced "perturbations," altering either tempo or phase in the middle of a presentation. Ronan quickly adjusted her behavior following all perturbations, recovering her consistent phase and tempo relationships to the stimulus within a few beats. Ronan's performance was consistent with predictions of mathematical models describing coupled oscillation: a model relying solely on phase coupling strongly matched her behavior, and the model was further improved with the addition of period coupling. These findings are the clearest evidence yet for parity in human and non-human beat keeping and support the view that the human ability to perceive and move in time to rhythm may be rooted in broadly conserved neural mechanisms.

  1. Beat Keeping in a Sea Lion as Coupled Oscillation: Implications for Comparative Understanding of Human Rhythm

    Directory of Open Access Journals (Sweden)

    Andrew A Rouse

    2016-06-01

    Full Text Available Human capacity for entraining movement to external rhythms—i.e., beat keeping—is ubiquitous, but its evolutionary history and neural underpinnings remain a mystery. Recent findings of entrainment to simple and complex rhythms in non-human animals pave the way for a novel comparative approach to assess the origins and mechanisms of rhythmic behavior. The most reliable non-human beat keeper to date is a California sea lion, Ronan, who was trained to match head movements to isochronous repeating stimuli and showed spontaneous generalization of this ability to novel tempos and to the complex rhythms of music. Does Ronan’s performance rely on the same neural mechanisms as human rhythmic behavior? In the current study, we presented Ronan with simple rhythmic stimuli at novel tempos. On some trials, we introduced perturbations, altering either tempo or phase in the middle of a presentation. Ronan quickly adjusted her behavior following all perturbations, recovering her consistent phase and tempo relationships to the stimulus within a few beats. Ronan’s performance was consistent with predictions of mathematical models describing coupled oscillation: a model relying solely on phase coupling strongly matched her behavior, and the model was further improved with the addition of period coupling. These findings are the clearest evidence yet for parity in human and non-human beat keeping and support the view that the human ability to perceive and move in time to rhythm may be rooted in broadly conserved neural mechanisms.

  2. Nicotinic acid receptor abnormalities in human skin cancer: implications for a role in epidermal differentiation.

    Directory of Open Access Journals (Sweden)

    Yira Bermudez

    Full Text Available BACKGROUND: Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells. RESULTS: Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional G(i-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional. CONCLUSIONS: The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s of nicotinic acid receptors in human skin homeostasis.

  3. Ethical attitudes on human cloning among professionals in Taiwan and the policy implications for regulation.

    Science.gov (United States)

    Yang, Che-Ming; Chung, Chun-Chih; Lu, Meei-Shiow; Lin, Chiou-Fen; Chen, Jiun-Shyan

    2005-01-01

    This research focused on understanding the attitudes toward human cloning in Taiwan among professionals in healthcare, law, and religion. The study was conducted utilizing a structured questionnaire. 220 healthcare professionals from two regional hospitals located in Taipei, 351 religious professionals in the northern Taiwan and 711 legal professionals were selected by to receive questionnaires. The valid response rate is 42.1% The questions were generated by an expert panel and represented major arguments in the human cloning debate. There were a total of six Likert scaled questions in the questionnaire. The responses were coded from 1 to 5 with 1 representing strong opposition to human cloning, 3 representing a neutral attitude; and 5 representing a strong favorable attitude toward human cloning. Healthcare professionals had the highest overall average score of 2.14 and the religious professionals had the lowest average at 1.58. All three categories of respondents' attitude toward cloning ranged from mild opposition to strong opposition to human cloning. The religious professionals were more strongly opposed to cloning. Age, education, and religion significantly influenced attitudes toward cloning. Professionals between fifty-one and sixty years old, those with less education, and Roman Catholic professionals were more strongly opposed to cloning. Religious professionals were more strongly opposed to human cloning than professionals in healthcare or law. Younger professionals as an age group demonstrated less opposition to human cloning. Regulation of human cloning will be influenced by professionals in healthcare, law, and religion, and the regulatory environment chosen now will play a pivotal role in influencing the acceptance of human cloning in the future.

  4. Human factors/ergonomics implications of big data analytics: Chartered Institute of Ergonomics and Human Factors annual lecture.

    Science.gov (United States)

    Drury, Colin G

    2015-01-01

    In recent years, advances in sensor technology, connectedness and computational power have come together to produce huge data-sets. The treatment and analysis of these data-sets is known as big data analytics (BDA), and the somewhat related term data mining. Fields allied to human factors/ergonomics (HFE), e.g. statistics, have developed computational methods to derive meaningful, actionable conclusions from these data bases. This paper examines BDA, often characterised by volume, velocity and variety, giving examples of successful BDA use. This examination provides context by considering examples of using BDA on human data, using BDA in HFE studies, and studies of how people perform BDA. Significant issues for HFE are the reliance of BDA on correlation rather than hypotheses and theory, the ethics of BDA and the use of HFE in data visualisation.

  5. Human-Computer Etiquette Cultural Expectations and the Design Implications They Place on Computers and Technology

    CERN Document Server

    Hayes, Caroline C

    2010-01-01

    Written by experts from various fields, this edited collection explores a wide range of issues pertaining to how computers evoke human social expectations. The book illustrates how socially acceptable conventions can strongly impact the effectiveness of human-computer interactions and how to consider such norms in the design of human-computer interfaces. Providing a complete introduction to the design of social responses to computers, the text emphasizes the value of social norms in the development of usable and enjoyable technology. It also describes the role of socially correct behavior in t

  6. Integrating the humanities in the education of health professionals: implications for search and retrieval of information.

    Science.gov (United States)

    Polson, Robert G; Farmer, Elizabeth S

    2002-03-01

    This article examines the increasing use of the humanities in the education of health professionals and posits that the approach may be of use in teaching health professionals information search and retrieval skills. However little evidence exists to support the educational effectiveness of using the humanities. This lack of evidence raises concerns about the costs of financing this approach to learning. These costs include the issue of copyright which cannot be ignored. While the humanities might provide a more attractive approach to teaching information search and retrieval skills, further research is needed to justify the costs of this approach to learning in more general terms and urgent attention to.

  7. Structural Features of Human Memapsin 2 (β-Secretase) and Their Biological and Pathological Implications

    Institute of Scientific and Technical Information of China (English)

    Lin HONG; Xiangyuan HE; Xiangping HUANG; Wanpin CHANG; Jordan TANG

    2004-01-01

    Memapsin 2 (β-secretase) is the membrane-anchored aspartic protease that initiates the cleavage of β-amyloid precursor protein (APP) leading to the production of amyloid-β (Aβ), a major factor in the pathogenesis of Alzheimer's disease (AD). Since memapsin 2 is a major target for the development of inhibitor drugs for AD, it has been intensively studied during the past five years. Here we discuss the structural features of the catalytic/specificity apparatus, transmembrane domain, cytosolic domain and the implications of these features in the physiological and pathological roles of this protease.

  8. Turn-taking in Human Communication--Origins and Implications for Language Processing.

    Science.gov (United States)

    Levinson, Stephen C

    2016-01-01

    Most language usage is interactive, involving rapid turn-taking. The turn-taking system has a number of striking properties: turns are short and responses are remarkably rapid, but turns are of varying length and often of very complex construction such that the underlying cognitive processing is highly compressed. Although neglected in cognitive science, the system has deep implications for language processing and acquisition that are only now becoming clear. Appearing earlier in ontogeny than linguistic competence, it is also found across all the major primate clades. This suggests a possible phylogenetic continuity, which may provide key insights into language evolution.

  9. Indoor air and human health: major indoor air pollutants and their health implications

    Energy Technology Data Exchange (ETDEWEB)

    1984-01-01

    This publication is a collection of abstracts of papers presented at the Indoor Air and Human Health symposium. Session titles include: Radon, Microorganisms, Passive Cigarette Smoke, Combustion Products, Organics, and Panel and Audience Discussion.

  10. Domestic violence on the Thai-Burma border: international human rights implications

    Directory of Open Access Journals (Sweden)

    Caroline Lambert

    2003-05-01

    Full Text Available This article focuses on domestic violence against womenliving in camps, highlighting both the potential and thelimitations of human rights standards in bringingchange to women’s lives.

  11. The human gut microbiome and body metabolism: implications for obesity and diabetes

    National Research Council Canada - National Science Library

    Devaraj, Sridevi; Hemarajata, Peera; Versalovic, James

    2013-01-01

    .... Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut...

  12. Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

    DEFF Research Database (Denmark)

    Belser, Jessica A; Blixt, Ola; Chen, Li-Mei

    2008-01-01

    Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom. The majority of H7 infections have resulted in self......-limiting conjunctivitis, whereas probable human-to-human transmission has been rare. Here, we used glycan microarray technology to determine the receptor-binding preference of Eurasian and North American lineage H7 influenza viruses and their transmissibility in the ferret model. We found that highly pathogenic H7N7...... in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact. These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and have...

  13. Implications of the evolution pattern of human T-cell leukemia retroviruses on their pathogenic virulence (Review).

    Science.gov (United States)

    Azran, Inbal; Schavinsky-Khrapunsky, Yana; Priel, Esther; Huleihel, Mahmoud; Aboud, Mordechai

    2004-11-01

    Simian retroviruses pose a serious threat to public health, as two human pathogenic retroviruses, HIV and HTLV, have been already proved to originate from such non-human viruses. Therefore, studying their natural prevalence among wild non-human primates is important for planning strategies to prevent the emergence of additional human retroviral pathogens. This article is focused on tracing the origin and evolution of the human T-cell leukemia viruses HTLV-I and HTLV-II in comparison to that of the simian lymphotropic viruses STLV-I, STLV-II and STLV-L, which are phylo-genically classified into a common group called primate T-lymphotropic viruses (PTLV). Thus, HTLV-I and STLV-I are referred to as PTLV-I and HTLV-II and STLV-II as PTLV-II, whereas STLV-L, which is highly divergent from both HTLV types, comprises a third subgroup called PTLV-L. The phylogeny of PTLV indicates that both, HTLV-I and HTLV-II emerged from a simian origin, but their subsequent evolution continued in different patterns. HTLV-I includes 6 subtypes which evolved from STLV-I through several times of different geographic interspecies transmission between simian and human hosts. These repeated invasions to new primate species are likely to give rise to viral strains with increasing pathogenic potential. On the other hand, HTLV-II includes 4 subtypes which appear to originate from a common human ancestor virus that emerged from only one simian to human transmission, whereas the subsequent evolution of HTLV-II and STLV-II strains continued separately only within the Homo sapiens and Pan paniscus species respectively, without repeated interspecies jumps. Such evolution pattern likely involves less genetic changes and selection of viral strains with low pathogenic virulence that could co-exist with their hosts for long time. These different evolution patterns can explain the much wider implication of HTLV-I with human clinical disorders than HTLV-II. Of note, however, more recently HTLV-II started

  14. Human nail plate modifications induced by onychomycosis: implications for topical therapy.

    OpenAIRE

    Baraldi, A.; S. A. Jones; Guesné, S.; Traynor, M.J.; McAuley, W.J.; Brown, M B; Murdan, S.

    2015-01-01

    Purpose Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations. Methods The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying wa...

  15. The Impact of Remittances on Human Development: A Quantitative Analysis and Policy Implications.

    OpenAIRE

    Üstübici, Ayşen; Irdam, Darja

    2012-01-01

    Abstract: This paper contributes to the discussions on the nexus between migration and development by assessing the effects of remittances on human development. We do so first through a quantitative approach, and second, by elaborating the findings of our quantitative analysis within a broader theoretical and policy framework. By using OLS, we measure the impact of remittances on human development and compare it with the effect of foreign direct investment (FDI) and official development assis...

  16. Brain response to a humanoid robot in areas implicated in the perception of human emotional gestures.

    Directory of Open Access Journals (Sweden)

    Thierry Chaminade

    Full Text Available BACKGROUND: The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. METHODOLOGY: Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. PRINCIPAL FINDINGS: Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. CONCLUSIONS: Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. SIGNIFICANCE: Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.

  17. Human migration patterns in Yemen and implications for reconstructing prehistoric population movements.

    Directory of Open Access Journals (Sweden)

    Aida T Miró-Herrans

    Full Text Available Population migration has played an important role in human evolutionary history and in the patterning of human genetic variation. A deeper and empirically-based understanding of human migration dynamics is needed in order to interpret genetic and archaeological evidence and to accurately reconstruct the prehistoric processes that comprise human evolutionary history. Current empirical estimates of migration include either short time frames (i.e. within one generation or partial knowledge about migration, such as proportion of migrants or distance of migration. An analysis of migration that includes both proportion of migrants and distance, and direction over multiple generations would better inform prehistoric reconstructions. To evaluate human migration, we use GPS coordinates from the place of residence of the Yemeni individuals sampled in our study, their birthplaces and their parents' and grandparents' birthplaces to calculate the proportion of migrants, as well as the distance and direction of migration events between each generation. We test for differences in these values between the generations and identify factors that influence the probability of migration. Our results show that the proportion and distance of migration between females and males is similar within generations. In contrast, the proportion and distance of migration is significantly lower in the grandparents' generation, most likely reflecting the decreasing effect of technology. Based on our results, we calculate the proportion of migration events (0.102 and mean and median distances of migration (96 km and 26 km for the grandparent's generation to represent early times in human evolution. These estimates can serve to set parameter values of demographic models in model-based methods of prehistoric reconstruction, such as approximate Bayesian computation. Our study provides the first empirically-based estimates of human migration over multiple generations in a developing

  18. Human migration patterns in Yemen and implications for reconstructing prehistoric population movements.

    Science.gov (United States)

    Miró-Herrans, Aida T; Al-Meeri, Ali; Mulligan, Connie J

    2014-01-01

    Population migration has played an important role in human evolutionary history and in the patterning of human genetic variation. A deeper and empirically-based understanding of human migration dynamics is needed in order to interpret genetic and archaeological evidence and to accurately reconstruct the prehistoric processes that comprise human evolutionary history. Current empirical estimates of migration include either short time frames (i.e. within one generation) or partial knowledge about migration, such as proportion of migrants or distance of migration. An analysis of migration that includes both proportion of migrants and distance, and direction over multiple generations would better inform prehistoric reconstructions. To evaluate human migration, we use GPS coordinates from the place of residence of the Yemeni individuals sampled in our study, their birthplaces and their parents' and grandparents' birthplaces to calculate the proportion of migrants, as well as the distance and direction of migration events between each generation. We test for differences in these values between the generations and identify factors that influence the probability of migration. Our results show that the proportion and distance of migration between females and males is similar within generations. In contrast, the proportion and distance of migration is significantly lower in the grandparents' generation, most likely reflecting the decreasing effect of technology. Based on our results, we calculate the proportion of migration events (0.102) and mean and median distances of migration (96 km and 26 km) for the grandparent's generation to represent early times in human evolution. These estimates can serve to set parameter values of demographic models in model-based methods of prehistoric reconstruction, such as approximate Bayesian computation. Our study provides the first empirically-based estimates of human migration over multiple generations in a developing country and these

  19. The human genome, implications for oral health and diseases, and dental education.

    Science.gov (United States)

    Slavkin, H C

    2001-05-01

    We are living in an extraordinary time in human history punctuated by the convergence of major scientific and technological progress in the physical, chemical, and biological ways of knowing. Equally extraordinary are the sparkling intellectual developments at the interface between fields of study. One major example of an emerging influence on the future of oral health education is at the interface between the human genome, information technology, and biotechnology with miniaturizations (nanotechnology), suggesting new oral health professional competencies for a new century. A great deal has recently been learned from human and non-human genomics. Genome databases are being "mined" to prompt hypothesis-driven "postgenomic" or functional genomic science in microbial models such as Candida albicans related to oral candidiasis and in human genomics related to biological processes found in craniofacial, oral, and dental diseases and disorders. This growing body of knowledge is already providing the gene content of many oral microbial and human genomes and the knowledge of genetic variants or polymorphisms related to disease, disease progression, and disease response to therapeutics (pharmacogenomics). The knowledge base from human and non-human genomics, functional genomics, biotechnology, and associated information technologies is serving to revolutionize oral health promotion, risk assessment using biomarkers and disease prevention, diagnostics, treatments, and the full range of therapeutics for craniofacial, oral, and dental diseases and disorders. Education, training, and research opportunities are already transforming the curriculum and pedagogy for undergraduate science majors, predoctoral health professional programs, residency and specialty programs, and graduate programs within the health professions. In the words of Bob Dylan, "the times they are a-changing."

  20. Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications

    OpenAIRE

    Garrido, Daniel; Dallas, David C; Mills, David A.

    2013-01-01

    Human milk is a rich source of nutrients and energy, shaped by mammalian evolution to provide all the nutritive requirements of the newborn. In addition, several molecules in breast milk act as bioactive agents, playing an important role in infant protection and guiding a proper development. While major breast milk nutrients such as lactose, lipids and proteins are readily digested and consumed by the infant, other molecules, such as human milk oligosaccharides and glycosylated proteins and l...

  1. Human Nail Plate Modifications Induced by Onychomycosis: Implications for Topical Therapy

    OpenAIRE

    Baraldi, A.; Jones, S.A.; Guesné, S.; Traynor, M. J.; McAuley, W J; Brown, M.B.; Murdan, S.

    2014-01-01

    Purpose Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations. Methods The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying wa...

  2. Human Migration Patterns in Yemen and Implications for Reconstructing Prehistoric Population Movements

    Science.gov (United States)

    Miró-Herrans, Aida T.; Al-Meeri, Ali; Mulligan, Connie J.

    2014-01-01

    Population migration has played an important role in human evolutionary history and in the patterning of human genetic variation. A deeper and empirically-based understanding of human migration dynamics is needed in order to interpret genetic and archaeological evidence and to accurately reconstruct the prehistoric processes that comprise human evolutionary history. Current empirical estimates of migration include either short time frames (i.e. within one generation) or partial knowledge about migration, such as proportion of migrants or distance of migration. An analysis of migration that includes both proportion of migrants and distance, and direction over multiple generations would better inform prehistoric reconstructions. To evaluate human migration, we use GPS coordinates from the place of residence of the Yemeni individuals sampled in our study, their birthplaces and their parents' and grandparents' birthplaces to calculate the proportion of migrants, as well as the distance and direction of migration events between each generation. We test for differences in these values between the generations and identify factors that influence the probability of migration. Our results show that the proportion and distance of migration between females and males is similar within generations. In contrast, the proportion and distance of migration is significantly lower in the grandparents' generation, most likely reflecting the decreasing effect of technology. Based on our results, we calculate the proportion of migration events (0.102) and mean and median distances of migration (96 km and 26 km) for the grandparent's generation to represent early times in human evolution. These estimates can serve to set parameter values of demographic models in model-based methods of prehistoric reconstruction, such as approximate Bayesian computation. Our study provides the first empirically-based estimates of human migration over multiple generations in a developing country and these

  3. Evolutionary continuity and personhood: Legal and therapeutic implications of animal consciousness and human unconsciousness.

    Science.gov (United States)

    Benvenuti, Anne

    Convergent lines of research in the biological sciences have made obsolete the commonly held assumption that humans are distinct from and superior to all other animals, a development predicted by evolutionary science. Cumulative evidence has both elevated other animals from the status of "dumb brutes" to that of fully sentient and intentional beings and has simultaneously discredited elevated claims of human rationality, intentionality, and freedom from the constraints experienced by other animals. It follows then that any theoretical model in which humans occupy the top of an imagined evolutionary hierarchy is untenable. This simple fact calls for a rethinking of foundational concepts in law and health sciences. A further cultural fallacy that is exposed by these converging lines of scientific evidence is the notion that the subjective inner and abstract dimension of human beings is the most true and valuable level of analysis for organizing human lives. In fact, our individual and collective minds are particularly vulnerable to elaborated false narratives that may be definitive of the particular forms of suffering that humans experience and seek to heal with modalities like psychoanalytic psychotherapies. I conclude with the suggestion that other animals may have the capacity to help us with this healing project, even as we are ethically bound to heal the suffering that we have collectively imposed upon them.

  4. Neuroscience Evidence for Economic Humanism in Management Science: Organizational Implications and Strategy.

    Science.gov (United States)

    Lattanzi, Nicola; Menicagli, Dario; Dal Maso, Lorenzo

    2016-04-01

    Globalization phenomena and Information Communication Technology (ICT) are producing deep changes worldwide. The economic environment and society where firms both cooperate and compete with each other are rapidly changing leading firms towards recognizing the role of intangible resources as a source of fresh competitive advantage. Experience, innovation and the ability to create new knowledge completely arise from the act of human resources inviting firms to focus on how to generate and shape knowledge. Therefore, the future of firms depends greatly on how managers are able to explore and exploit human resources. However, without a clear understanding of the nature of human beings and the complexity behind human interactions, we cannot understand the theory of organizational knowledge creation. Thus, how can firms discover, manage and valorize this "human advantage"? Neuroscience can increase the understanding of how cognitive and emotional processes work; in doing so, we may be able to better understand how individuals involved in a business organization make decisions and how external factors influence their behavior, especially in terms of commitment activation and engagement level. In this respect, a neuroscientific approach to business can support managers in decision-making processes. In a scenario where economic humanism plays a central role in the process of fostering firms' competitiveness and emerging strategies, we believe that a neuroscience approach in a business organization could be a valid source of value and inspiration for manager decision-making processes.

  5. Social diversity in humans: implications and hidden consequences for biological research.

    Science.gov (United States)

    Duster, Troy

    2014-05-01

    Humans are both similar and diverse in such a vast number of dimensions that for human geneticists and social scientists to decide which of these dimensions is a worthy focus of empirical investigation is a formidable challenge. For geneticists, one vital question, of course, revolves around hypothesizing which kind of social diversity might illuminate genetic variation-and vice versa (i.e., what genetic variation illuminates human social diversity). For example, are there health outcomes that can be best explained by genetic variation-or for social scientists, are health outcomes mainly a function of the social diversity of lifestyles and social circumstances of a given population? Indeed, what is a "population," how is it bounded, and are those boundaries most appropriate or relevant for human genetic research, be they national borders, religious affiliation, ethnic or racial identification, or language group, to name but a few? For social scientists, the matter of what constitutes the relevant borders of a population is equally complex, and the answer is demarcated by the goal of the research project. Although race and caste are categories deployed in both human genetics and social science, the social meaning of race and caste as pathways to employment, health, or education demonstrably overwhelms the analytic and explanatory power of genetic markers of difference between human aggregates.

  6. Evaluating the Photoprotective Effects of Ochre on Human Skin by In Vivo SPF Assessment: Implications for Human Evolution, Adaptation and Dispersal.

    Science.gov (United States)

    Rifkin, Riaan F; Dayet, Laure; Queffelec, Alain; Summers, Beverley; Lategan, Marlize; d'Errico, Francesco

    2015-01-01

    Archaeological indicators of cognitively modern behaviour become increasingly prevalent during the African Middle Stone Age (MSA). Although the exploitation of ochre is viewed as a key feature of the emergence of modern human behaviour, the uses to which ochre and ochre-based mixtures were put remain ambiguous. Here we present the results of an experimental study exploring the efficacy of ochre as a topical photoprotective compound. This is achieved through the in vivo calculation of the sun protection factor (SPF) values of ochre samples obtained from Ovahimba women (Kunene Region, Northern Namibia) and the Palaeozoic Bokkeveld Group deposits of the Cape Supergroup (Western Cape Province, South Africa). We employ visible spectroscopy, energy-dispersive X-ray fluorescence (ED-XRF), X-ray diffraction (XRD) and granulometric analyses to characterise ochre samples. The capacity of ochre to inhibit the susceptibility of humans to the harmful effects of exposure to ultraviolet radiation (UVR) is confirmed and the mechanisms implicated in the efficacy of ochre as a sunscreen identified. It is posited that the habitual application of ochre may have represented a crucial innovation for MSA humans by limiting the adverse effects of ultraviolet exposure. This may have facilitated the colonisation of geographic regions largely unfavourable to the constitutive skin colour of newly arriving populations.

  7. Evaluating the Photoprotective Effects of Ochre on Human Skin by In Vivo SPF Assessment: Implications for Human Evolution, Adaptation and Dispersal.

    Directory of Open Access Journals (Sweden)

    Riaan F Rifkin

    Full Text Available Archaeological indicators of cognitively modern behaviour become increasingly prevalent during the African Middle Stone Age (MSA. Although the exploitation of ochre is viewed as a key feature of the emergence of modern human behaviour, the uses to which ochre and ochre-based mixtures were put remain ambiguous. Here we present the results of an experimental study exploring the efficacy of ochre as a topical photoprotective compound. This is achieved through the in vivo calculation of the sun protection factor (SPF values of ochre samples obtained from Ovahimba women (Kunene Region, Northern Namibia and the Palaeozoic Bokkeveld Group deposits of the Cape Supergroup (Western Cape Province, South Africa. We employ visible spectroscopy, energy-dispersive X-ray fluorescence (ED-XRF, X-ray diffraction (XRD and granulometric analyses to characterise ochre samples. The capacity of ochre to inhibit the susceptibility of humans to the harmful effects of exposure to ultraviolet radiation (UVR is confirmed and the mechanisms implicated in the efficacy of ochre as a sunscreen identified. It is posited that the habitual application of ochre may have represented a crucial innovation for MSA humans by limiting the adverse effects of ultraviolet exposure. This may have facilitated the colonisation of geographic regions largely unfavourable to the constitutive skin colour of newly arriving populations.

  8. Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity.

    Science.gov (United States)

    van Hees, Vincent T; Gorzelniak, Lukas; Dean León, Emmanuel Carlos; Eder, Martin; Pias, Marcelo; Taherian, Salman; Ekelund, Ulf; Renström, Frida; Franks, Paul W; Horsch, Alexander; Brage, Søren

    2013-01-01

    Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics) of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment. An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one [ENMO], Euclidian norm of the high-pass filtered signals [HFEN], and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g [HFEN+]) were derived for each experimental condition and compared against the reference acceleration (forward kinematics) of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22-65 yr), and wrist in 63 women (20-35 yr) in whom daily activity-related energy expenditure (PAEE) was available. In the robot experiment, HFEN+ had lowest error during (vertical plane) rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively). ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN). In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice of metric explains different degrees of variance in

  9. Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity.

    Directory of Open Access Journals (Sweden)

    Vincent T van Hees

    Full Text Available INTRODUCTION: Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment. METHODS: An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one [ENMO], Euclidian norm of the high-pass filtered signals [HFEN], and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g [HFEN+] were derived for each experimental condition and compared against the reference acceleration (forward kinematics of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22-65 yr, and wrist in 63 women (20-35 yr in whom daily activity-related energy expenditure (PAEE was available. RESULTS: In the robot experiment, HFEN+ had lowest error during (vertical plane rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively. ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN. CONCLUSION: In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice

  10. Dissociating object directed and non-object directed action in the human mirror system; implications for theories of motor simulation.

    Directory of Open Access Journals (Sweden)

    Zarinah K Agnew

    Full Text Available Mirror neurons are single cells found in macaque premotor and parietal cortices that are active during action execution and observation. In non-human primates, mirror neurons have only been found in relation to object-directed movements or communicative gestures, as non-object directed actions of the upper limb are not well characterized in non-human primates. Mirror neurons provide important evidence for motor simulation theories of cognition, sometimes referred to as the direct matching hypothesis, which propose that observed actions are mapped onto associated motor schemata in a direct and automatic manner. This study, for the first time, directly compares mirror responses, defined as the overlap between action execution and observation, during object directed and meaningless non-object directed actions. We present functional MRI data that demonstrate a clear dissociation between object directed and non-object directed actions within the human mirror system. A premotor and parietal network was preferentially active during object directed actions, whether observed or executed. Moreover, we report spatially correlated activity across multiple voxels for observation and execution of an object directed action. In contrast to predictions made by motor simulation theory, no similar activity was observed for non-object directed actions. These data demonstrate that object directed and meaningless non-object directed actions are subserved by different neuronal networks and that the human mirror response is significantly greater for object directed actions. These data have important implications for understanding the human mirror system and for simulation theories of motor cognition. Subsequent theories of motor simulation must account for these differences, possibly by acknowledging the role of experience in modulating the mirror response.

  11. Early dispersal of modern humans in Europe and implications for Neanderthal behaviour.

    Science.gov (United States)

    Benazzi, Stefano; Douka, Katerina; Fornai, Cinzia; Bauer, Catherine C; Kullmer, Ottmar; Svoboda, Jiří; Pap, Ildikó; Mallegni, Francesco; Bayle, Priscilla; Coquerelle, Michael; Condemi, Silvana; Ronchitelli, Annamaria; Harvati, Katerina; Weber, Gerhard W

    2011-11-02

    The appearance of anatomically modern humans in Europe and the nature of the transition from the Middle to Upper Palaeolithic are matters of intense debate. Most researchers accept that before the arrival of anatomically modern humans, Neanderthals had adopted several 'transitional' technocomplexes. Two of these, the Uluzzian of southern Europe and the Châtelperronian of western Europe, are key to current interpretations regarding the timing of arrival of anatomically modern humans in the region and their potential interaction with Neanderthal populations. They are also central to current debates regarding the cognitive abilities of Neanderthals and the reasons behind their extinction. However, the actual fossil evidence associated with these assemblages is scant and fragmentary, and recent work has questioned the attribution of the Châtelperronian to Neanderthals on the basis of taphonomic mixing and lithic analysis. Here we reanalyse the deciduous molars from the Grotta del Cavallo (southern Italy), associated with the Uluzzian and originally classified as Neanderthal. Using two independent morphometric methods based on microtomographic data, we show that the Cavallo specimens can be attributed to anatomically modern humans. The secure context of the teeth provides crucial evidence that the makers of the Uluzzian technocomplex were therefore not Neanderthals. In addition, new chronometric data for the Uluzzian layers of Grotta del Cavallo obtained from associated shell beads and included within a Bayesian age model show that the teeth must date to ~45,000-43,000 calendar years before present. The Cavallo human remains are therefore the oldest known European anatomically modern humans, confirming a rapid dispersal of modern humans across the continent before the Aurignacian and the disappearance of Neanderthals.

  12. Antigen-specific acquired immunity in human brucellosis: implications for diagnosis, prognosis, and vaccine development

    Directory of Open Access Journals (Sweden)

    Anthony P Cannella

    2012-02-01

    Full Text Available Brucella spp. are facultative intracellular Gram negative bacteria with specific tropism for monocytes/macrophages. Clinical manifestations of brucellosis are primarily immune-mediated and not thought to be due to bacterial virulence factors. Acquired immunity to brucellosis has been studied through observations of naturally infected hosts (cattle, goats, laboratory mouse models, and human infection. Cell-mediated immunity drives the clinical manifestations of human disease after exposure to Brucella species but high antibody responses are not associated with protective immunity. The precise mechanisms by which cell-mediated immune responses confer protection or lead to disease manifestations remain poorly understood. Descriptive studies of immune responses in human brucellosis show that TH1 (interferon-gamma are associated with dominant immune responses, findings consistent with animal studies. Whether these T cell responses are protective, or determine the different clinical responses associated with brucellosis is unknown, especially with regard to undulant fever manifestations, relapsing disease, or are associated with responses to distinct sets of Brucella spp. antigens are unknown. Few data regarding T cell responses in terms of specific recognition of Brucella spp. protein antigens and peptidic epitopes, either by CD4+ or CD8+ T cells, have been identified in human brucellosis patients. Additionally because current attenuated Brucella vaccines used in animals cause human disease, there is a true need for a recombinant protein subunit vaccine for human brucellosis, as well as for improved diagnostics in terms of prognosis and identification of unusual forms of brucellosis. This review will focus on current understandings of antigen-specific immune responses induced by Brucella protein antigens that has promise for yielding new insights into vaccine and diagnostics development, and for understanding pathogenetic mechanisms of human

  13. Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP Proteins with Implications for Human Disease

    Directory of Open Access Journals (Sweden)

    Marshall V. Williams

    2016-12-01

    Full Text Available The human herpesviruses are ubiquitous viruses and have a prevalence of over 90% in the adult population. Following a primary infection they establish latency and can be reactivated over a person’s lifetime. While it is well accepted that human herpesviruses are implicated in numerous diseases ranging from dermatological and autoimmune disease to cancer, the role of lytic proteins in the pathophysiology of herpesvirus-associated diseases remains largely understudies. Only recently have we begun to appreciate the importance of lytic proteins produced during reactivation of the virus, in particular the deoxyuridine triphosphate nucleotidohydrolases (dUTPase, as key modulators of the host innate and adaptive immune responses. In this review, we provide evidence from animal and human studies of the Epstein–Barr virus as a prototype, supporting the notion that herpesviruses dUTPases are a family of proteins with unique immunoregulatory functions that can alter the inflammatory microenvironment and thus exacerbate the immune pathology of herpesvirus-related diseases including myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune diseases, and cancer.

  14. Gorilla and orangutan brains conform to the primate cellular scaling rules: implications for human evolution.

    Science.gov (United States)

    Herculano-Houzel, Suzana; Kaas, Jon H

    2011-01-01

    Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they

  15. Covert Sexual Signaling: Human Flirtation and Implications for other Social Species

    Directory of Open Access Journals (Sweden)

    Andrew Gersick

    2014-07-01

    Full Text Available According to signaling theory and a large body of supporting evidence, males across many taxa produce courtship signals that honestly advertise their quality. The cost of producing or performing these signals maintains signal honesty, such that females are typically able to choose the best males by selecting those that produce the loudest, brightest, longest, or otherwise highest-intensity signals, using signal strength as a measure of quality. Set against this background, human flirting behavior, characterized by its frequent subtlety or covertness, is mysterious. Here we propose that the explanation for subtle and ambiguous signals in human courtship lies in socially imposed costs that (a vary with social context and (b are amplified by the unusual ways in which language makes all interactions potentially public. Flirting is a class of courtship signaling that conveys the signaler's intentions and desirability to the intended receiver while minimizing the costs that would accompany an overt courtship attempt. This proposal explains humans' taxonomically unusual courtship displays and generates a number of novel predictions for both humans and non-human social animals. Individuals who are courting should vary the intensity of their signals to suit the level of risk attached to the particular social configuration, and receivers may assess this flexible matching of signal to context as an indicator of the signaler's broader behavioral flexibility and social intelligence.

  16. Monkey-based research on human disease: the implications of genetic differences.

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists.

  17. Scientific misconduct and unethical human experimentation: historic parallels and moral implications.

    Science.gov (United States)

    Lefor, Alan T

    2005-01-01

    Although a great deal of human experimentation has been performed to elucidate information otherwise not obtainable, there are many recorded instances of unethical human experimentation. There is also a history of crimes that were committed and disguised as human experiments, best exemplified by the activities of some physicians in Nazi Germany from 1933 until 1945. As a direct result of these activities, a war-crimes trial after World War II resulted in the creation of the Nuremberg Code, to guide future human experimentation. Despite this, unethical experiments were conducted at major academic institutions in the United States in the years after World War II by otherwise normal physicians who did not feel that the Nuremberg Code applied to them personally. There are several possible explanations for such activities, but the desire for personal advancement is prominent among these. Episodes of scientific misconduct such as falsification of experimental data or of personal qualifications seem to be more commonly reported recently and have also been described in the popular press. This activity may also be motivated by desire for personal advancement, giving it a parallel to the conduct of unethical human experimentation. Education may be the best way to prevent these activities that may have similar motivating factors.

  18. Pioglitazone increases the glycolytic efficiency of human Sertoli cells with possible implications for spermatogenesis.

    Science.gov (United States)

    Meneses, M J; Bernardino, R L; Sá, R; Silva, J; Barros, A; Sousa, M; Silva, B M; Oliveira, P F; Alves, M G

    2016-10-01

    Pioglitazone is a synthetic agonist for the nuclear receptor peroxisome proliferator-activated receptor γ used to treat type 2 diabetes mellitus. Recently we reported that antidiabetic drugs regulate the nutritional support of spermatogenesis by Sertoli cells. Herein, we investigate the effects of pioglitazone on human Sertoli cells metabolism. Human Sertoli cells were cultured in the presence of pioglitazone (1, 10, 100μM). Protein levels of phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot. Lactate dehydrogenase and alanine aminotransferase activity were assessed and metabolite production and consumption determined by proton nuclear magnetic resonance. Mitochondrial membrane potential was also determined. Glucose consumption more than doubled in human Sertoli cells stimulated with pioglitazone 100μM. Mitochondrial complex II protein levels increased 50% with exposure to pioglitazone (100μM) in human Sertoli cells, though mitochondrial membrane potential was decreased by 32%. The pharmacological concentration of pioglitazone (10μM) almost doubled lactate production and established crucial correlations among key intervenient of glycolysis. Moreover, in the same concentration, alanine aminotransferase decreased more than 80%. Our results suggest that pioglitazone (10μM) increases the efficiency of the glycolytic flux and lactate production by human Sertoli cells, which is essential to sustain and preserve the spermatogenic event. Thus, pioglitazone may improve male fertility and thus, be considered a suitable antidiabetic drug for men in reproductive age.

  19. Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence: Implications for human genetic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, R.L. (Univ. of Pittsburgh, PA (United States))

    1994-05-01

    The distribution of all trinucleotide microsatellite sequences in the GenBank database was surveyed to provide insight into human genetic disease syndromes that result from expansion of microsatellites. The microsatellite motif (CAG)[sub n] is one of the most abundant microsatellite motifs in human GenBank DNA sequences and is the most abundant microsatellite found in exons. This fact may explain why (CAG)[sub n] repeats are thus far the predominant microsatellites expanded in human genetic diseases. Surprisingly, (CAG)[sub n] microsatellites are excluded from intronic regions in a strand-specific fashion, possibly because of similarity to the 3[prime] consensus splice site, CAGG. A comparison of the positions of microsatellites in human vs rodent homologous sequences indicates that some arrays are not extensively conserved for long periods of time, even when they form parts of protein coding sequences. The general lack of conservation of trinucleotide repeat loci in diverse mammals indicates that animal models for some human microsatellite expansion syndromes may be difficult to find. 20 refs., 5 tabs.

  20. Rural Dwellers’ Perception of Human Trafficking and its Implication for Agricultural Production in Edo State, Nigeria

    Directory of Open Access Journals (Sweden)

    Ofuoku, A. U.

    2012-09-01

    Full Text Available This study was carried out to ascertain the perception of rural dwellers on human trafficking in relation to its effect on agricultural production in the three Senatorial Districts of Edo State, Nigeria. A sample size of 120 household heads was used for the study. Structured questionnaire and interview schedule were used to collect data for the study. The data were analyzed using frequency counts, means and percentage while Chi-Square statistical model and Tobit regression analytical model were used to test the hypotheses. It was discovered that the household members were trafficked as a result of push and pull factors. The trafficked members of household were actively involved in farming practices before being trafficked. There is significant relationship between human trafficking and agriculture production. Shortage of farm labor, decreased farm size, reduced farm income, reduced farm output, extra expenditure on hired labor and storage of food supply by the community were perceived as effect of human trafficking on agriculture. Age of the household head and the household size had significant effect on the number of household member trafficked. Human trafficking has an adverse effect on agricultural production. Extension department should therefore integrate anti-human trafficking campaigns with their services to the farming population.

  1. Rabbit Model of Human Gliomas: Implications for Intra-Arterial Drug Delivery

    Science.gov (United States)

    Qin, Huamin; Janowski, Miroslaw; Pearl, Monica S.; Malysz-Cymborska, Izabela; Li, Shen; Eberhart, Charles G.

    2017-01-01

    The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices. To date, however, no protocols are available that enable human glioma modeling in rabbits. In this article, we report on the xenotransplantation of a human glioblastoma (GBM-1) in adult New Zealand rabbits. We induced multi-drug immunosuppression (Mycophenolate Mofetil, Dexamethasone, Tacrolimus) and stereotactically implanted GBM-1 tumor cells into rabbit brains. The rabbits were followed for 42 days, monitored by MRI and body weight measurements, and underwent postmortem histopathological analysis. On MRI, brain tumors were identified on T2-weighted scans. On histopathology, tumors were detected with hematoxylin/eosin and their human origin was confirmed with immunohistochemistry against human-specific antigens. Our method for human glioma modeling in rabbits provides the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery. PMID:28103265

  2. Wastewater reuse in irrigation: a microbiological perspective on implications in soil fertility and human and environmental health.

    Science.gov (United States)

    Becerra-Castro, Cristina; Lopes, Ana Rita; Vaz-Moreira, Ivone; Silva, Elisabete F; Manaia, Célia M; Nunes, Olga C

    2015-02-01

    The reuse of treated wastewater, in particular for irrigation, is an increasingly common practice, encouraged by governments and official entities worldwide. Irrigation with wastewater may have implications at two different levels: alter the physicochemical and microbiological properties of the soil and/or introduce and contribute to the accumulation of chemical and biological contaminants in soil. The first may affect soil productivity and fertility; the second may pose serious risks to the human and environmental health. The sustainable wastewater reuse in agriculture should prevent both types of effects, requiring a holistic and integrated risk assessment. In this article we critically review possible effects of irrigation with treated wastewater, with special emphasis on soil microbiota. The maintenance of a rich and diversified autochthonous soil microbiota and the use of treated wastewater with minimal levels of potential soil contaminants are proposed as sine qua non conditions to achieve a sustainable wastewater reuse for irrigation.

  3. Integrating Public Health and Deliberative Public Bioethics: Lessons from the Human Genome Project Ethical, Legal, and Social Implications Program.

    Science.gov (United States)

    Meagher, Karen M; Lee, Lisa M

    2016-01-01

    Public health policy works best when grounded in firm public health standards of evidence and widely shared social values. In this article, we argue for incorporating a specific method of ethical deliberation--deliberative public bioethics--into public health. We describe how deliberative public bioethics is a method of engagement that can be helpful in public health. Although medical, research, and public health ethics can be considered some of what bioethics addresses, deliberative public bioethics offers both a how and where. Using the Human Genome Project Ethical, Legal, and Social Implications program as an example of effective incorporation of deliberative processes to integrate ethics into public health policy, we examine how deliberative public bioethics can integrate both public health and bioethics perspectives into three areas of public health practice: research, education, and health policy. We then offer recommendations for future collaborations that integrate deliberative methods into public health policy and practice.

  4. Human factors that derail extension services delivery in developing countries: implications for policy

    Directory of Open Access Journals (Sweden)

    E.N. Ajani

    2012-12-01

    Full Text Available The paper examines human factors derailing extension services delivery in developing countries. Poor management of rewards and incentives; quality of work life; poor assessment system; limited quality of human resource; inadequate extension support training materials; inconsistencies of government programmes; inadequate staff training and poor extension programme evaluation were viewed as major constraints. Considering the role of extension to agricultural development, the paper recommends that efforts should be made by the various stakeholders in agricultural extension services to improve the capability of human resources involved in extension services and highlights the need for government agricultural programmes to be consistent to enable the beneficiaries of such programmes derive the benefits that will boost productivity in agriculture.

  5. Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M. (Stanford Univ. School of Medicine, CA (USA))

    1990-10-01

    Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.

  6. Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease.

    Science.gov (United States)

    Ginns, E I; Choudary, P V; Tsuji, S; Martin, B; Stubblefield, B; Sawyer, J; Hozier, J; Barranger, J A

    1985-01-01

    Analysis of immunologic cross-reacting material in Chinese hamster-human somatic cell hybrids allowed assignment of the structural gene for glucocerebrosidase (glucosylceramidase; beta-D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45) to chromosome 1 bands q21-q32. In situ hybridization of a radiolabeled human glucocerebrosidase cDNA to high resolution human chromosomes demonstrated that a single locus encoding glucocerebrosidase is on 1q21, adjacent to a region of chromosome 1 (1qh) abundant in structural heteromorphisms. We also have identified a hydrophobic leader polypeptide encoded by this locus, permitting a more complete description of the biosynthesis of the enzyme. These results suggest that the type-specific protein polymorphisms in Gaucher disease result from mutations at this single locus, whose segregation might be followed by linkage to visible chromosomal heteromorphisms. Images PMID:3863141

  7. Arsenic speciation in Chinese Herbal Medicines and human health implication for inorganic arsenic.

    Science.gov (United States)

    Liu, Xiao-Juan; Zhao, Quan-Li; Sun, Guo-Xin; Williams, Paul; Lu, Xiu-Jun; Cai, Jing-Zhu; Liu, Wen-Ju

    2013-01-01

    Rice and drinking water are recognized as the dominant sources of arsenic (As) for human intake, while little is known about As accumulation and speciation in Chinese Herbal Medicines (CHMs), which have been available for many hundreds of years for the treatment of diseases in both eastern and western cultures. Inorganic arsenic was the predominant species in all of CHMs samples. The levels of inorganic arsenic in CHMs from fields and markets or pharmacies ranged from 63 to 550 ng/g with a mean of 208 ng/g and 94 to 8683 ng/g with a mean of 1092 ng/g, respectively. The highest concentration was found in the Chrysanthemum from pharmacies. It indicates that the risk of inorganic As in CHMs to human health is higher in medicines from markets or pharmacies than that collected directly from fields. Some CHMs may make a considerable contribution to the human intake of inorganic arsenic.

  8. Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution.

    Science.gov (United States)

    Zihlman, Adrienne L; Bolter, Debra R

    2015-06-16

    The human body has been shaped by natural selection during the past 4-5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition.

  9. Heavy ions, radioprotectors and genomic instability: implications for human space exploration.

    Science.gov (United States)

    Dziegielewski, Jaroslaw; Goetz, Wilfried; Baulch, Janet E

    2010-08-01

    The risk associated with space radiation exposure is unique from terrestrial radiation exposures due to differences in radiation quality, including linear energy transfer (LET). Both high- and low-LET radiations are capable of inducing genomic instability in mammalian cells, and this instability is thought to be a driving force underlying radiation carcinogenesis. Unfortunately, during space exploration, flight crews cannot entirely avoid radiation exposure. As a result, chemical and biological countermeasures will be an important component of successful extended missions such as the exploration of Mars. There are currently several radioprotective agents (radioprotectors) in use; however, scientists continue to search for ideal radioprotective compounds-safe to use and effective in preventing and/or reducing acute and delayed effects of irradiation. This review discusses the agents that are currently available or being evaluated for their potential as radioprotectors. Further, this review discusses some implications of radioprotection for the induction and/or propagation of genomic instability in the progeny of irradiated cells.

  10. Clinical implications of epigenetic alterations in human thoracic malignancies: epigenetic alterations in lung cancer.

    Science.gov (United States)

    Shinjo, Keiko; Kondo, Yutaka

    2012-01-01

    Besides known genetic aberrations, epigenetic alterations have emerged as common hallmarks of many cancer types, including lung cancer. Epigenetics is a process involved in gene regulation, mediated via DNA methylation, histone modification, chromatin remodeling, and functional noncoding RNAs, which influences the accessibility of the underlying DNA to transcriptional regulatory factors that activate or repress expression. Studies have shown that epigenetic dysregulation is associated with multiple steps during carcinogenesis. Since epigenetic therapy is now in clinical use in hematopoietic diseases and undergoing trials for lung cancer, a better understanding of epigenetic abnormalities is desired. Recent technologies for high-throughput genome-wide analyses for epigenetic modifications are promising and potent tools for understanding the global dysregulation of cancer epigenetics. In this chapter, studies of epigenetic abnormality and its clinical implication in lung cancers are discussed.

  11. Chromosomal Mosaicism in Human Feto-Placental Development: Implications for Prenatal Diagnosis

    Directory of Open Access Journals (Sweden)

    Francesca Romana Grati

    2014-07-01

    Full Text Available Chromosomal mosaicism is one of the primary interpretative issues in prenatal diagnosis. In this review, the mechanisms underlying feto-placental chromosomal mosaicism are presented. Based on the substantial retrospective diagnostic experience with chorionic villi samples (CVS of a prenatal diagnosis laboratory the following items are discussed: (i The frequency of the different types of mosaicism (confined placental, CPM, and true fetal mosaicisms, TFM; (ii The risk of fetal confirmation after the detection of a mosaic in CVS stratified by chromosome abnormality and placental tissue involvement; (iii The frequency of uniparental disomy for imprinted chromosomes associated with CPM; (iv The incidence of false-positive and false-negative results in CVS samples analyzed by only (semi-direct preparation or long term culture; and (v The implications of the presence of a feto-placental mosaicism for microarray analysis of CVS and non-invasive prenatal screening (NIPS.

  12. Rowing, the ultimate challenge to the human body - implications for physiological variables

    DEFF Research Database (Denmark)

    Volianitis, S.; Secher, Niels H.

    2009-01-01

    Clinical diagnoses depend on a variety of physiological variables but the full range of these variables is seldom known. With the load placed on the human body during competitive rowing, the physiological range for several variables is illustrated. The extreme work produced during rowing...... is explained by the seated position and the associated ability to increase venous return and, thus, cardiac output. This review highlights experimental work on Olympic rowing that presents a unique challenge to the human capacities, including cerebral metabolism, to unprecedented limits, and provides a unique...

  13. Global Survey on Future Trends in Human Spaceflight: the Implications for Space Tourism

    Science.gov (United States)

    Gurtuna, O.; Garneau, S.

    2002-01-01

    With the much-publicized first ever space tourist flight, of Dennis Tito, and the announcement of the second space tourist flight to take place in April 2002, it is clear that an alternative motivation for human spaceflight has emerged. Human spaceflight is no longer only about meeting the priorities of national governments and space agencies, but is also about the tangible possibility of ordinary people seeing the Earth from a previously exclusive vantage point. It is imperative that major space players look beyond the existing human spaceflight rationale to identify some of the major driving forces behind space tourism, including the evolving market potential and developments in enabling technologies. In order to determine the influence of these forces on the future of commercial human spaceflight, the responses of a Futuraspace survey on future trends in human spaceflight are analyzed and presented. The motivation of this study is to identify sought-after space destinations, explore the expected trends in enabling technologies, and understand the future role of emerging space players. The survey will reflect the opinions of respondents from around the world including North America, Europe (including Russia) and Asia. The profiles of targeted respondents from space industry, government and academia are high-level executives/managers, senior researchers, as well as former and current astronauts. The survey instrument is a questionnaire which is validated by a pilot study. The sampling method is non-probabilistic, targeting as many space experts as possible who fit our intended respondent profile. Descriptive and comparative statistical analysis methods are implemented to investigate both global and regional perceptions of future commercial trends in human spaceflight. This study is not intended to be a formal market study of the potential viability of the space tourism market. Instead, the focus is on the future trends of human spaceflight, by drawing on the

  14. Early Upper Paleolithic in Eastern Europe and implications for the dispersal of modern humans.

    Science.gov (United States)

    Anikovich, M V; Sinitsyn, A A; Hoffecker, John F; Holliday, Vance T; Popov, V V; Lisitsyn, S N; Forman, Steven L; Levkovskaya, G M; Pospelova, G A; Kuz'mina, I E; Burova, N D; Goldberg, Paul; Macphail, Richard I; Giaccio, Biagio; Praslov, N D

    2007-01-12

    Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation-probably representing modern humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia.

  15. Human health implications associated with mucilage in the northern Adriatic Sea.

    Science.gov (United States)

    Funari, E; Ade, P

    1999-01-01

    Mucilage in the northern Adriatic Sea is well known for its negative impact not only on the ecology of the affected area and on fishing activities but on tourism as well. The microhabitat mucilage creates in the sea can provide favourable conditions for the growth and/or survival of some environmental microorganisms that include human opportunistic pathogens. It also seems to favour the selective development of some marine toxic algae. Finally, mucilage can concentrate chemical contaminants from surrounding waters, hence increasing their bioaccumulation in seafoods. This paper examines the possible direct and indirect effects on human health of mucilage and other forms of marine aggregates.

  16. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    Science.gov (United States)

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study.

  17. School Principals' Assumptions about Human Nature: Implications for Leadership in Turkey

    Science.gov (United States)

    Sabanci, Ali

    2008-01-01

    This article considers principals' assumptions about human nature in Turkey and the relationship between the assumptions held and the leadership style adopted in schools. The findings show that school principals hold Y-type assumptions and prefer a relationship-oriented style in their relations with assistant principals. However, both principals…

  18. Psychology of human kin recognition : Heuristic cues, erroneous inferences, and their implications

    NARCIS (Netherlands)

    Park, Justin H.; Schaller, Mark; Van Vugt, Mark

    Humans possess explicit, rule-based, and culturally determined systems for identifying kin, but kinship inferences are also influenced implicitly by cue-based mechanisms found commonly across the animal kingdom. These mechanisms are fallible. An evolutionarily informed signal-detection analysis

  19. Epigenetic modifications in human fragile X pluripotent stem cells; Implications in fragile X syndrome modeling.

    Science.gov (United States)

    Gerhardt, Jeannine

    2017-02-01

    Patients with fragile X syndrome (FXS) exhibit moderate to severe intellectual disabilities. In addition, one-third of FXS patients show characteristics of autism spectrum disorder. FXS is caused by a trinucleotide repeat expansion, which leads to silencing of the fragile X mental retardation (FMR1) gene. The absence of the FMR1 gene product, FMRP, is the reason for the disease symptoms. It has been suggested that repeat instability and transcription of the FMR1 gene occur during early embryonic development, while after cell differentiation repeats become stable and the FMR1 gene is silent. Epigenetic marks, such as DNA methylation, are associated with gene silencing and repeat stability at the FMR1 locus. However, the mechanisms leading to gene silencing and repeat expansion are still ambiguous, because studies at the human genomic locus were limited until now. The FXS pluripotent stem cells, recently derived from FXS adult cells and FXS blastocysts, are new useful tools to examine these mechanisms at the human endogenous FMR1 locus. This review summarizes the epigenetic features and experimental studies of FXS human embryonic and FXS induced pluripotent stem cells, generated so far. This article is part of a Special Issue entitled SI: Exploiting human neurons.

  20. Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases.

    Science.gov (United States)

    Shekhawat, Prem; Bennett, Michael J; Sadovsky, Yoel; Nelson, D Michael; Rakheja, Dinesh; Strauss, Arnold W

    2003-06-01

    The role of fat metabolism during human pregnancy and in placental growth and function is poorly understood. Mitochondrial fatty acid oxidation disorders in an affected fetus are associated with maternal diseases of pregnancy, including preeclampsia, acute fatty liver of pregnancy, and the hemolysis, elevated liver enzymes, and low platelets syndrome called HELLP. We have investigated the developmental expression and activity of six fatty acid beta-oxidation enzymes at various gestational-age human placentas. Placental specimens exhibited abundant expression of all six enzymes, as assessed by immunohistochemical and immunoblot analyses, with greater staining in syncytiotrophoblasts compared with other placental cell types. beta-Oxidation enzyme activities in placental tissues were higher early in gestation and lower near term. Trophoblast cells in culture oxidized tritium-labeled palmitate and myristate in substantial amounts, indicating that the human placenta utilizes fatty acids as a significant metabolic fuel. Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy.

  1. Teachers' Perspectives on the Human-Nature Relationship: Implications for Environmental Education

    Science.gov (United States)

    Almeida, Antonio; Vasconcelos, Clara

    2013-01-01

    This study based on a theoretical framework of three main environmental perspectives in the human-nature relationship (anthropocentrism, biocentrism and ecocentrism), aimed to identify their incidence in teachers involved with environmental projects when confronted with diverse environmental issues. 60 teachers drawn from four school cycles in…

  2. Psychology of human kin recognition : Heuristic cues, erroneous inferences, and their implications

    NARCIS (Netherlands)

    Park, Justin H.; Schaller, Mark; Van Vugt, Mark

    2008-01-01

    Humans possess explicit, rule-based, and culturally determined systems for identifying kin, but kinship inferences are also influenced implicitly by cue-based mechanisms found commonly across the animal kingdom. These mechanisms are fallible. An evolutionarily informed signal-detection analysis sugg

  3. Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health.

    Science.gov (United States)

    Wasielewski, Helen; Alcock, Joe; Aktipis, Athena

    2016-05-01

    Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host-microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting from microbiome-host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host-microbe interactions may be novel targets for interventions aimed at improving nutrition and human health.

  4. Sociability and gazing toward humans in dogs and wolves: Simple behaviors with broad implications.

    Science.gov (United States)

    Bentosela, Mariana; Wynne, C D L; D'Orazio, M; Elgier, A; Udell, M A R

    2016-01-01

    Sociability, defined as the tendency to approach and interact with unfamiliar people, has been found to modulate some communicative responses in domestic dogs, including gaze behavior toward the human face. The objective of this study was to compare sociability and gaze behavior in pet domestic dogs and in human-socialized captive wolves in order to identify the relative influence of domestication and learning in the development of the dog-human bond. In Experiment 1, we assessed the approach behavior and social tendencies of dogs and wolves to a familiar and an unfamiliar person. In Experiment 2, we compared the animal's duration of gaze toward a person's face in the presence of food, which the animals could see but not access. Dogs showed higher levels of interspecific sociability than wolves in all conditions, including those where attention was unavailable. In addition, dogs gazed longer at the person's face than wolves in the presence of out-of-reach food. The potential contributions of domestication, associative learning, and experiences during ontogeny to prosocial behavior toward humans are discussed. © 2016 Society for the Experimental Analysis of Behavior.

  5. Psychology of human kin recognition : Heuristic cues, erroneous inferences, and their implications

    NARCIS (Netherlands)

    Park, Justin H.; Schaller, Mark; Van Vugt, Mark

    2008-01-01

    Humans possess explicit, rule-based, and culturally determined systems for identifying kin, but kinship inferences are also influenced implicitly by cue-based mechanisms found commonly across the animal kingdom. These mechanisms are fallible. An evolutionarily informed signal-detection analysis sugg

  6. Women in STEM and Human Information Behavior: Implications for LIS Educators

    Science.gov (United States)

    Davis, Rebecca

    2014-01-01

    This paper reports preliminary data from research that seeks to inform the readers about the way that human information behavior and the use of scholarly resources impacts on women in the STEM fields. By focusing on the information behavior and information needs of women in STEM, this could lead to an increased use of academic library resources…

  7. AMPK and the biochemistry of exercise: implications for human health and disease

    DEFF Research Database (Denmark)

    Richter, Erik; Ruderman, Neil B.

    2009-01-01

    AMPK (AMP-activated protein kinase) is a phylogenetically conserved fuel-sensing enzyme that is present in all mammalian cells. During exercise, it is activated in skeletal muscle in humans, and at least in rodents, also in adipose tissue, liver and perhaps other organs by events that increase th...

  8. Aneuploidy screening of human IVF embryos: Cytogenetic aspects and clinical implications

    NARCIS (Netherlands)

    E.B. Baart (Esther)

    2007-01-01

    textabstractThe introduction of this thesis provides the reader with the necessary background information to understand the rationale behind the studies conducted. It starts with the observation that human incidence of chromosomal abnormalities in oocytes and embryos. Furthermore, an explanation

  9. Humans and Autonomy: Implications of Shared Decision Making for Military Operations

    Science.gov (United States)

    2017-01-01

    interaction. In: Shumaker R, Lackey S, editors. Virtual, augmented and mixed reality : designing and developing virtual and augmented environments...R, Lackey S, editors. Virtual, augmented and mixed reality : designing and developing virtual and augmented environments. Berlin (Germany): Springer...Mort G. Augmenting Soldier situation awareness and navigation through tactile cueing. Proceedings of the 17th International Conference on Human

  10. Dietary fiber analysis of common pulses using AOAC 2011.25: Implications for human health

    Science.gov (United States)

    Dietary fiber is an important non-nutritive component of food and is believed to have various benefits to human health. In many countries, such as the United States and Canada, the intake of dietary fiber is 50 to 70% below recommended levels in greater than 95% of the population. We recently adva...

  11. Making Sense of Women as Career Self-Agents: Implications for Human Resource Development

    Science.gov (United States)

    Shapiro, Mary; Ingols, Cynthia; O'Neill, Regina; Blake-Beard, Stacy

    2009-01-01

    In this article, we explore the shifting career paradigm of managerial women in the United States, what it may indicate for the broader professional workforce, and human resource development's (HRD's) role in supporting that change. We examine the literature on evolving career definitions, women's place in that evolution, the rising use of…

  12. Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

    Science.gov (United States)

    Ronsoni, Marcelo Fernando; Remor, Aline Pertile; Lopes, Mark William; Hohl, Alexandre; Troncoso, Iris H Z; Leal, Rodrigo Bainy; Boos, Gustavo Luchi; Kondageski, Charles; Nunes, Jean Costa; Linhares, Marcelo Neves; Lin, Kátia; Latini, Alexandra Susana; Walz, Roger

    2016-04-01

    Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery.

  13. Legal and Ethical Implications of Using Social Media in Human Resource Management

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2014-06-01

    Full Text Available Now more than ever we live in a society saturated with technology and media.  We are captured by the technology whirlwind such as the internet, instant messages, emails, and social media such as Twitter and Facebook.  Technologies not only are changing the way people live, work, and interact with each other but also the way companies conduct their businesses.  Social media no doubt is one of such technologies that enables companies to market their products and services in new and unique dimensions.  Beyond marketing, social media is also changing the way human resource professionals recruit and select employees.   Recruiting and selecting potential new employees using social media, is gaining popularity.  There are even software programs that capitalize on the information available on social media sites to assist human resources professionals to source, screen, and track job applicants.  Although there are many advantages in using social media networks to assist HR to select and filter job candidates, there are reasons for concerns.  In this paper, we’ll examine the legal and ethical consequences of using social media in the area of human resource management.   Keywords: Social Media, Facebook, Human Resources, Management.

  14. Andragogy and Social Capital Theory: The Implications for Human Resource Development

    NARCIS (Netherlands)

    Kessels, Joseph W.M.; Poell, Rob F.

    2004-01-01

    The problem and the solution. This article portrays a perspective from andragogy, individual learning, and social capital theory as a contribution to the discussion on the relationship between adult learning theory and human resource development (HRD). Andragogy and social capital theory may offer a

  15. Andragology and social capital theory: the implications for human resource development

    NARCIS (Netherlands)

    Kessels, Joseph; Poell, Rob F.

    2004-01-01

    The problem and the solution. This article portrays a perspective from andragogy, individual learning, and social capital theory as a contribution to the discussion on the relationship between adult learning theory and human resource development (HRD). Andragogy and social capital theory may offer a

  16. A Formal Investigation of the Organization of Guidance Behavior: Implications for Humans and Autonomous Guidance

    Science.gov (United States)

    Kong, Zhaodan

    Guidance behavior generated either by artificial agents or humans has been actively studied in the fields of both robotics and cognitive science. The goals of these two fields are different. The former is the automatic generation of appropriate or even optimal behavior, while the latter is the understanding of the underlying mechanism. Their challenges, though, are closely related, the most important one being the lack of a unified, formal and grounded framework where the guidance behavior can be modeled and studied. This dissertation presents such a framework. In this framework, guidance behavior is analyzed as the closed-loop dynamics of the whole agent-environment system. The resulting dynamics give rise to interaction patterns. The central points of this dissertation are that: first of all, these patterns, which can be explained in terms of symmetries that are inherent to the guidance behavior, provide building blocks for the organization of behavior; second, the existence of these patterns and humans' organization of their guidance behavior based on these patterns are the reasons that humans can generate successful behavior in spite of all the complexities involved in the planning and control. This dissertation first gives an overview of the challenges existing in both scientific endeavors, such as human and animal spatial behavior study, and engineering endeavors, such as autonomous guidance system design. It then lays out the foundation for our formal framework, which states that guidance behavior should be interpreted as the collection of the closed-loop dynamics resulting from the agent's interaction with the environment. The following, illustrated by examples of three different UAVs, shows that the study of the closed-loop dynamics should not be done without the consideration of vehicle dynamics, as is the common practice in some of the studies in both autonomous guidance and human behavior analysis. The framework, the core concepts of which are

  17. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

    Science.gov (United States)

    Cunnane, Stephen C; Crawford, Michael A

    2014-12-01

    The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development.

  18. Midtarsal break variation in modern humans: Functional causes, skeletal correlates, and paleontological implications.

    Science.gov (United States)

    DeSilva, J M; Bonne-Annee, R; Swanson, Z; Gill, C M; Sobel, M; Uy, J; Gill, S V

    2015-04-01

    The midtarsal break was once treated as a dichotomous, non-overlapping trait present in the foot of non-human primates and absent in humans. Recent work indicates that there is considerable variation in human midfoot dorsiflexion, with some overlap with the ape foot. These findings have called into question the uniqueness of the human lateral midfoot, and the use of osteological features in fossil hominins to characterize the midfoot of our extinct ancestors. Here, we present data on plantar pressure and pedal mechanics in a large sample of adults and children (n = 671) to test functional hypotheses concerning variation in midfoot flexibility. Lateral midfoot peak plantar pressure correlates with both sagittal plane flexion at the lateral tarsometatarsal joint, and dorsiflexion at the hallucal metatarsophalangeal joint. The latter finding suggests that midfoot laxity may compromise hallucal propulsion. Multiple regression statistics indicate that a low arch and pronation of the foot explain 40% of variation in midfoot peak plantar pressure, independent of age and BMI. MRI scans on a small subset of study participants (n = 19) reveals that curvature of the base of the 4th metatarsal correlates with lateral midfoot plantar pressure and that specific anatomies of foot bones do indeed reflect relative midfoot flexibility. However, while the shape of the base of the 4th metatarsal may reliably reflect midfoot mobility in individual hominins, given the wide range of overlapping variation in midfoot flexibility in both apes and humans, we caution against generalizing foot function in extinct hominin species until larger fossils samples are available. © 2015 Wiley Periodicals, Inc.

  19. The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

    Directory of Open Access Journals (Sweden)

    Bin Qiu

    2016-08-01

    Full Text Available FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1 Fkbp5 KO and wild-type (WT EtOH consumption was tested using a two-bottle choice paradigm; (2 The EtOH elimination rate was measured after intraperitoneal (IP injection of 2.0 g/kg EtOH; (3 Blood alcohol concentration (BAC was measured after 3 h limited access of alcohol; (4 Brain region expression of Fkbp5 was identified using LacZ staining; (5 Baseline corticosterone (CORT was assessed. Additionally, two SNPs, rs1360780 (C/T and rs3800373 (T/G, were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162 from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT. Finally, single nucleotide polymorphisms (SNPs in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.

  20. The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans.

    Science.gov (United States)

    Qiu, Bin; Luczak, Susan E; Wall, Tamara L; Kirchhoff, Aaron M; Xu, Yuxue; Eng, Mimy Y; Stewart, Robert B; Shou, Weinian; Boehm, Stephen L; Chester, Julia A; Yong, Weidong; Liang, Tiebing

    2016-08-05

    FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21-26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.

  1. The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

    Science.gov (United States)

    Qiu, Bin; Luczak, Susan E.; Wall, Tamara L.; Kirchhoff, Aaron M.; Xu, Yuxue; Eng, Mimy Y.; Stewart, Robert B.; Shou, Weinian; Boehm, Stephen L.; Chester, Julia A.; Yong, Weidong; Liang, Tiebing

    2016-01-01

    FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans. PMID:27527158

  2. Advances in understanding of mammalian penile evolution, human penile anatomy and human erection physiology: clinical implications for physicians and surgeons.

    Science.gov (United States)

    Hsieh, Cheng-Hsing; Liu, Shih-Ping; Hsu, Geng-Long; Chen, Heng-Shuen; Molodysky, Eugen; Chen, Ying-Hui; Yu, Hong-Jeng

    2012-07-01

    Recent studies substantiate a model of the tunica albuginea of the corpora cavernosa as a bi-layered structure with a 360° complete inner circular layer and a 300° incomplete outer longitudinal coat spanning from the bulbospongiosus and ischiocavernosus proximally and extending continuously into the distal ligament within the glans penis. The anatomical location and histology of the distal ligament invites convincing parallels with the quadrupedal os penis and therefore constitutes potential evidence of the evolutionary process. In the corpora cavernosa, a chamber design is responsible for facilitating rigid erections. For investigating its venous factors exclusively, hemodynamic studies have been performed on both fresh and defrosted human male cadavers. In each case, a rigid erection was unequivocally attainable following venous removal. This clearly has significant ramifications in relation to penile venous surgery and its role in treating impotent patients. One deep dorsal vein, 2 cavernosal veins and 2 pairs of para-arterial veins (as opposed to 1 single vein) are situated between Buck's fascia and the tunica albuginea. These newfound insights into penile tunical, venous anatomy and erection physiology were inspired by and, in turn, enhance clinical applications routinely encountered by physicians and surgeons, such as penile morphological reconstruction, penile implantation and penile venous surgery.

  3. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: ikerr@myriad.com [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: ikerr@myriad.com [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  4. Earthing: Health Implications of Reconnecting the Human Body to the Earth's Surface Electrons

    Directory of Open Access Journals (Sweden)

    Gaétan Chevalier

    2012-01-01

    Full Text Available Environmental medicine generally addresses environmental factors with a negative impact on human health. However, emerging scientific research has revealed a surprisingly positive and overlooked environmental factor on health: direct physical contact with the vast supply of electrons on the surface of the Earth. Modern lifestyle separates humans from such contact. The research suggests that this disconnect may be a major contributor to physiological dysfunction and unwellness. Reconnection with the Earth's electrons has been found to promote intriguing physiological changes and subjective reports of well-being. Earthing (or grounding refers to the discovery of benefits—including better sleep and reduced pain—from walking barefoot outside or sitting, working, or sleeping indoors connected to conductive systems that transfer the Earth's electrons from the ground into the body. This paper reviews the earthing research and the potential of earthing as a simple and easily accessed global modality of significant clinical importance.

  5. Epigenetics: definition, molecular bases and implications in human health and evolution

    Directory of Open Access Journals (Sweden)

    García-Robles Reggie

    2012-04-01

    Full Text Available Epigenetics refers to inheritable changes in DNA and histones that do not involve changes in thesequence of nucleotides and that modifies structure and chromatin condensation, thus affectinggene expression and phenotype. Epigenetic modifications are DNA methylation and histone modifications. Objective: A review of the literature on the concept of Epigenetics and its impacton health. Materials and methods: A review of the literature was performed on the concept ofepigenetics, its biological basis, the impact on health and disease and its relation to evolution.Results: Epigenetic mechanisms have become increasingly important because of the growingassociation with common complex diseases as well as its impact on health of future generationsand in human evolution. Conclusions: Epigenetics has a clear impact on the health of individualsin their offspring and with the evolution of the human species

  6. Soil-transmitted helminthiases: implications of climate change and human behavior.

    Science.gov (United States)

    Weaver, Haylee J; Hawdon, John M; Hoberg, Eric P

    2010-12-01

    Soil-transmitted helminthiases (STHs) collectively cause the highest global burden of parasitic disease after malaria and are most prevalent in the poorest communities, especially in sub-Saharan Africa. Climate change is predicted to alter the physical environment through cumulative impacts of warming and extreme fluctuations in temperature and precipitation, with cascading effects on human health and wellbeing, food security and socioeconomic infrastructure. Understanding how the spectrum of climate change effects will influence STHs is therefore of critical importance to the control of the global burden of human parasitic disease. Realistic progress in the global control of STH in a changing climate requires a multidisciplinary approach that includes the sciences (e.g. thermal thresholds for parasite development and resilience) and social sciences (e.g. behavior and implementation of education and sanitation programs). Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Human health implications of Salmonella-contaminated natural pet treats and raw pet food.

    Science.gov (United States)

    Finley, Rita; Reid-Smith, Richard; Weese, J Scott

    2006-03-01

    Human salmonellosis occurs mainly as a result of handling or consuming contaminated food products, with a small percentage of cases being related to other, less well-defined exposures, such as contact with companion animals and natural pet treats. The increasing popularity of raw food diets for companion animals is another potential pet-associated source of Salmonella organisms; however, no confirmed cases of human salmonellosis have been associated with these diets. Pets that consume contaminated pet treats and raw food diets can be colonized with Salmonella organisms without exhibiting clinical signs, making them a possible hidden source of contamination in the household. Pet owners can reduce their risk of acquiring Salmonella organisms by not feeding natural pet treats and raw food diets to their pets, whereas individuals who investigate cases of salmonellosis or interpret surveillance data should be aware of these possible sources of Salmonella organisms.

  8. Canine diabetes mellitus has a seasonal incidence: implications relevant to human diabetes.

    Science.gov (United States)

    Atkins, C E; MacDonald, M J

    1987-06-01

    A 3 year survey of practicing veterinarians in the State of Wisconsin revealed a strong seasonal variation (peak incidence in January and February) for spontaneous canine diabetes mellitus (SCDM) in pet dogs. This seasonal incidence was quite similar to that observed in insulin-dependent diabetes mellitus (IDDM) in humans. SCDM is etiologically heterogeneous, it has dissimilar etiologies as compared to IDDM, and it is unlikely that viral infections play a causal role. For these reasons, it is concluded that the finding of a similar seasonal incidence in SCDM and IDDM suggests that the seasonal incidence of IDDM most likely represents the effects of, as yet undefined, stresses which precipitate the diabetic state in humans and dogs with pre-existent islet dysfunction of varying causes.

  9. Zika virus: A new human teratogen? Implications for women of reproductive age.

    Science.gov (United States)

    Schuler-Faccini, L; Sanseverino, Mtv; Vianna, Fsl; da Silva, A A; Larrandaburu, M; Marcolongo-Pereira, C; Abeche, A M

    2016-07-01

    In 2015 an unprecedented increase of reports of newborns with microcephaly in Brazil made news headlines around the world. A possible etiological association with prenatal maternal infection by Zika virus (ZIKV) was suggested based on temporal and geographic distribution of ZIKV infection and the subsequent increase in the reports of microcephaly cases. Here we discuss ZIKV as a new human teratogen, with comments on potential treatment options.

  10. The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans

    OpenAIRE

    Pant, Vinod; Quintás-Cardama, Alfonso; Lozano, Guillermina

    2012-01-01

    Aberrations in the p53 tumor suppressor pathway are associated with hematologic malignancies. p53-dependent cell cycle control, senescence, and apoptosis functions are actively involved in maintaining hematopoietic homeostasis under normal and stress conditions. Whereas loss of p53 function promotes leukemia and lymphoma development in humans and mice, increased p53 activity inhibits hematopoietic stem cell function and results in myelodysplasia. Thus, exquisite regulation of p53 activity is ...

  11. Linkages Between Human Capital and the Environment: Implications for Sustainable Econmic Development

    OpenAIRE

    Goetz, Stephan J.; Debertin, David L.; Pagoulatos, Angelos

    1997-01-01

    An empirical analysis reveals that US states with a more highly educated population have better environmental conditions, after controlling for income and industrial composition. The strategy of raising human capital stocks to maintain or improve environmental quality is proposed as a complement, if not an alternative, to direct government intervention which consists of command and control, market incentives and moral suasion. Under this approach, general education becomes the control variabl...

  12. Mechanisms of quinolone resistance and implications for human and animal health

    Directory of Open Access Journals (Sweden)

    Velhner Maja

    2010-01-01

    Full Text Available Quinolone antibiotics have been widely used in human and veterinary medicine. This has caused the development of resistance and difficulties in the treatment of complicated bacterial infections in humans. The resistance to quinolones develops due to chromosome mutations and it can also be transferred by plasmids. The target enzyme for quinolones in Gram-negative bacteria is Gyrasa A, while the target enzyme in Grampositive bacteria is mostly topoisomerase IV. Gyrase A consists of two subunits encoded by genes gyrA and gyrB. The function of the enzyme is to introduce negative super coiling in DNA and therefore is essential for the replication of bacteria. Quinolone resistance develops if point mutations at 83 and/or 87 codon are introduced on gyrA. Establishing a minimal inhibitory concentration (MIC to this group of antimicrobials will reveal possible mutations. Recently it was discovered that quinolone resistance is transmittable by plasmid termed PMQR (plasmid mediated quinolone resistance. The target gene marked qnr encodes a pentapeptide repeat family protein. Pentapeptide repeats form sheets, involved in protein-protein interactions. Qnr protein binds to GyrA protecting the enzyme from the inhibitory effect of ciprofloxacin. The distribution of qnr related resistance is higher in humans than in animals. In poultry, however, this type of resistance is present more than in other animals. Plasmid mediated resistance contributes to the faster spread of quinolone resistance. Proper food handling will significantly contribute to decreasing the risk from infection to which people are exposed. In medical and veterinary laboratories antimicrobial resistance monitoring in clinical and environmental isolates is advised. Since correlation between antibiotics application and antimicrobial resistance is often suggested, antimicrobial use must be under strict control of the authorities both in human and in veterinary medicine. .

  13. Enzymatic amplification of synthetic oligodeoxyribonucleotides: implications for triplet repeat expansions in the human genome.

    Science.gov (United States)

    Behn-Krappa, A; Doerfler, W

    1994-01-01

    The triplet repeat sequences (CGG)n, (GCT)n, and (CAG)n, which naturally occur in the human genome, can be autonomously expanded in human DNA by an as yet unknown mechanism. These in part excessive expansions have been causally related to human genetic diseases, the fragile X (Martin-Bell) syndrome, to myotonic dystrophy (Curschmann-Steinert), to spinal and bulbar muscular atrophy (Kennedy disease), and recently to Huntington disease. A GCC trinucleotide repeat was found to be expanded and methylated in the fragile site FRAXE on the human X chromosome. These findings were associated with mental retardation (Knight et al., 1993). In spinocerebellar ataxia type 1 (SCA1), a polymorphic CAG repeat was found to be unstable and expanded in individuals with that disease (Orr et al., 1993). We have demonstrated in in vitro experiments that the synthetic oligodeoxyribonucleotides (CGG)17, (CGG)12, (GCC)17, (CG)25, (CTG)17, or (CAG)17 plus (GTC)17, in the absence of added natural DNA, can be expanded with Taq polymerase in the polymerase chain reaction (PCR). Some expansion can already be detected after 4 PCR cycles. The E. coli Klenow DNA polymerase also functions in a similar amplification and expansion reaction performed at 37 degrees C without cycling. Other oligodeoxyribonucleotides, like, (CGG)7, (CGGT)13, or (TAA)17, are devoid of this property or have very low activity. The cytidine-methylated polymers (GCC)17 or (CG)25 yield expansion products of considerably reduced chain lengths. The expansion of the polymer (CGG)17 is affected by cytidine methylation to a lesser degree. A specific sequence and/or secondary structure and high CG content appear to be requirements for this expansion reaction by a possible slippage mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. COMMENTARY: GLOBALIZATION, HEALTH SECTOR REFORM, AND THE HUMAN RIGHT TO HEALTH: IMPLICATIONS FOR FUTURE HEALTH POLICY.

    Science.gov (United States)

    Schuftan, Claudio

    2015-01-01

    The author here distills his long-time personal experience with the deleterious effects of globalization on health and on the health sector reforms embarked on in many of the more than 50 countries where he has worked in the last 25 years. He highlights the role that the "human right to health" framework can and should play in countering globalization's negative effects on health and in shaping future health policy. This is a testimonial article.

  15. Posttranslational modifications of human M3 muscarinic acetylcholine receptor: zooming in its functional implications

    OpenAIRE

    Romero Fernández, Wilber

    2011-01-01

    The human M3 muscarinic acetylcholine receptor (M3R) regulates many important physiological roles in the central and peripheral nervous systems, and it is involved in the pathophysiology of several neurodegenerative and autoimmune diseases, representing attractive potential pharmacological target for intervention. However, the lack of structural information on this receptor hampered the development of new potent antagonist with increased selectivity and lower side effects. Such structural inf...

  16. Chimpanzee hand preference for throwing and infant cradling:implications for the origin of human handedness

    OpenAIRE

    Hopkins, William D.; Kim A Bard; Jones, A; Bales, S. L.

    1993-01-01

    Calvin (i983) has hypothesized that the neurophysiological, perceptual, and cognitive demands of throwing may have served as important evolutionary precursors to a variety of traits( e.g., handedness, tool use, and language processing) in early hominids. Eighty-eight percent of humans throw with their right hands (Healey, Liederman, and Geschwind I986), and Calvin has argued that this right-handed throwing evolved as a result of a left-hemisphere specialization for planned sequential movement...

  17. Biological and Analytical Variation of the Human Sweating Response: Implications for Study Design and Analysis

    Science.gov (United States)

    2012-01-01

    information http://www.the-aps.org/publications/ajpregu This infomation is current as of January 24, 2012. ISSN: 0363-6119, ESSN: 1522-1490. Visit our...sweating rate; reproducibility; exercise-heat stress; sweating onset A FUNDAMENTAL CHALLENGE IN the study of human integrative physiology is in the...analysis software. Analytical variation. To determine the ventilated sweat capsule measurement system CVa, measurements of SR were made in an

  18. The European Court of Human Rights: Implications for United States National Security

    Science.gov (United States)

    2014-02-04

    to the Geneva Convention) to climate change ( Kyoto Protocols ) to arms control (Comprehensive Nuclear Test-Ban Treaty), including those related to...instruments that it perceives will encroach on its sovereignty. There are a wide variety of such treaties, from human rights (Additional Protocols I & II...Rights.” 5 In 1998, with the adoption of Protocol No. 11, individuals were allowed to petition the court directly, but only after exhausting their

  19. Recognition, Reification, and Practices of Forgetting: Ethical Implications of Human Resource Management

    OpenAIRE

    Islam, Gazi

    2012-01-01

    International audience; This article examines the ethical framing of employment in contemporary human resource management (HRM). Using Axel Honneth's theory of recognition and classical critical notions of reification, I contrast recognition and reifying stances on labor. The recognition approach embeds work in its emotive and social particu-larity, positively affirming the basic dignity of social actors. Reifying views, by contrast, exhibit a forgetfulness of recognition, removing action fro...

  20. Human nail plate modifications induced by onychomycosis: implications for topical therapy.

    Science.gov (United States)

    Baraldi, A; Jones, S A; Guesné, S; Traynor, M J; McAuley, W J; Brown, M B; Murdan, S

    2015-05-01

    Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations. The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail's density was determined via pycnometry and the nail's ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake. Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm(3); diseased 1.29 ± 0.00 g/cm(3)). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle. Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.

  1. A human cellular sequence implicated in trk oncogene activation is DNA damage inducible

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Ishai, R.; Scharf, R.; Sharon, R.; Kapten, I. (Technion-Israel Institute of Technology, Haifa (Israel))

    1990-08-01

    Xeroderma pigmentosum cells, which are deficient in the repair of UV light-induced DNA damage, have been used to clone DNA-damage-inducible transcripts in human cells. The cDNA clone designated pC-5 hybridizes on RNA gel blots to a 1-kilobase transcript, which is moderately abundant in nontreated cells and whose synthesis is enhanced in human cells following UV irradiation or treatment with several other DNA-damaging agents. UV-enhanced transcription of C-5 RNA is transient and occurs at lower fluences and to a greater extent in DNA-repair-deficient than in DNA-repair-proficient cells. Southern blot analysis indicates that the C-5 gene belongs to a multigene family. A cDNA clone containing the complete coding sequence of C-5 was isolated. Sequence analysis revealed that it is homologous to a human cellular sequence encoding the amino-terminal activating sequence of the trk-2h chimeric oncogene. The presence of DNA-damage-responsive sequences at the 5' end of a chimeric oncogene could result in enhanced expression of the oncogene in response to carcinogens.

  2. Complex origins of breadfruit (Artocarpus altilis, Moraceae): implications for human migrations in Oceania.

    Science.gov (United States)

    Zerega, Nyree J C; Ragone, Diane; Motley, Timothy J

    2004-05-01

    Breadfruit (Artocarpus altilis, Moraceae), a traditional starch crop in Oceania, has enjoyed legendary status ever since its role in the infamous mutiny aboard the H.M.S. Bounty in 1789, yet its origins remain unclear. Breadfruit's closest relatives are A. camansi and A. mariannensis. DNA fingerprinting data (AFLP, amplified fragment length polymorphisms) from over 200 breadfruit cultivars, 30 A. camansi, and 24 A. mariannensis individuals were used to investigate the relationships among these species. Multivariate analyses and the identification of species-specific AFLP markers indicate at least two origins of breadfruit. Most Melanesian and Polynesian cultivars appear to have arisen over generations of vegetative propagation and selection from A. camansi. In contrast, most Micronesian breadfruit cultivars appear to be the result of hybridization between A. camansi-derived breadfruit and A. mariannensis. Because breadfruit depends on humans for dispersal, the data were compared to theories on the human colonization of Oceania. The results agree with the well-supported theory that humans settled Polynesia via Melanesia. Additionally, a long-distance migration from eastern Melanesia into Micronesia is supported.

  3. (13) C-metabolic flux analysis of human adenovirus infection: Implications for viral vector production.

    Science.gov (United States)

    Carinhas, Nuno; Koshkin, Alexey; Pais, Daniel A M; Alves, Paula M; Teixeira, Ana P

    2017-01-01

    Adenoviruses are human pathogens increasingly used as gene therapy and vaccination vectors. However, their impact on cell metabolism is poorly characterized. We performed carbon labeling experiments with [1,2-(13) C]glucose or [U-(13) C]glutamine to evaluate metabolic alterations in the amniocyte-derived, E1-transformed 1G3 cell line during production of a human adenovirus type 5 vector (AdV5). Nonstationary (13) C-metabolic flux analysis revealed increased fluxes of glycolysis (17%) and markedly PPP (over fourfold) and cytosolic AcCoA formation (nearly twofold) following infection of growing cells. Interestingly, infection of growth-arrested cells increased overall carbon flow even more, including glutamine anaplerosis and TCA cycle activity (both over 1.5-fold), but was unable to stimulate the PPP and was associated with a steep drop in AdV5 replication (almost 80%). Our results underscore the importance of nucleic and fatty acid biosynthesis for adenovirus replication. Overall, we portray a metabolic blueprint of human adenovirus infection, highlighting similarities with other viruses and cancer, and suggest strategies to improve AdV5 production. Biotechnol. Bioeng. 2017;114: 195-207. © 2016 Wiley Periodicals, Inc.

  4. Uptake of inorganic mercury by human locus ceruleus and corticomotor neurons: implications for amyotrophic lateral sclerosis

    Science.gov (United States)

    2013-01-01

    Background Environmental toxins are suspected to play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In an attempt to determine which pathways these toxins can use to enter motor neurons we compared the distribution of mercury in the CNS of a human and of mice that had been exposed to inorganic mercury. Results In the human who had been exposed to metallic mercury, mercury was seen predominantly in the locus ceruleus and corticomotor neurons, as well as in scattered glial cells. In mice that had been exposed to mercury vapor or mercuric chloride, mercury was present in lower motor neurons in the spinal cord and brain stem. Conclusions In humans, inorganic mercury can be taken up predominantly by corticomotor neurons, possibly when the locus ceruleus is upregulated by stress. This toxin uptake into corticomotor neurons is in accord with the hypothesis that ALS originates in these upper motor neurons. In mice, inorganic mercury is taken up predominantly by lower motor neurons. The routes toxins use to enter motor neurons depends on the nature of the toxin, the duration of exposure, and possibly the amount of stress (for upper motor neuron uptake) and exercise (for lower motor neuron uptake) at the time of toxin exposure. PMID:24252585

  5. Pathological implications of Cx43 down-regulation in human colon cancer.

    Science.gov (United States)

    Ismail, Rehana; Rashid, Rabiya; Andrabi, Khurshid; Parray, Fazl Q; Besina, Syed; Shah, Mohd Amin; Ul Hussain, Mahboob

    2014-01-01

    Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (pcancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.

  6. Transfer of oxytetracycline from swine manure to three different aquatic plants: implications for human exposure.

    Science.gov (United States)

    Boonsaner, Maliwan; Hawker, Darryl W

    2015-03-01

    Little is known regarding the potential for pharmaceuticals including antibiotics to be accumulated in edible aquatic plants and enter the human food chain. This work investigates the transfer of a widely used veterinary antibiotic, oxytetracycline (OTC), from swine manure to aquatic plants by firstly characterizing desorption from swine manure to water and fitting data to both nonlinear and linear isotherms. Bioconcentration of OTC from water was then quantified with aquatic plants of contrasting morphology and growth habit viz. watermeal (Wolffia globosa Hartog and Plas), cabomba (Cabomba caroliniana A. Gray) and water spinach (Ipomoea aquatica Forsk.). Watermeal and water spinach are widely consumed in Southeast Asia. The OTC desorption and bioconcentration data were used to provide the first quantitative estimates of human exposure to OTC from a manure-water-aquatic plant route. Results show that under certain conditions (plants growing for 15d in undiluted swine manure effluent (2% w/v solids) and an initial OTC swine manure concentration of 43mgkg(-1) (dry weight)), this pathway could provide a significant fraction (>48%) of the acceptable daily intake (ADI) for OTC. While effluent dilution, lower OTC manure concentrations and not all plant material consumed being contaminated would be expected to diminish the proportion of the ADI accumulated, uptake from aquatic plants should not be ignored when determining human exposure to antibiotics such as OTC.

  7. Human rhabdomyosarcoma cells express functional pituitary and gonadal sex hormone receptors: Therapeutic implications

    Science.gov (United States)

    PONIEWIERSKA-BARAN, AGATA; SCHNEIDER, GABRIELA; SUN, WENYUE; ABDELBASET-ISMAIL, AHMED; BARR, FREDERIC G.; RATAJCZAK, MARIUSZ Z.

    2016-01-01

    Evidence has accumulated that sex hormones play an important role in several types of cancer. Because they are also involved in skeletal muscle development and regeneration, we were therefore interested in their potential involvement in the pathogenesis of human rhabdomyosarcoma (RMS), a skeletal muscle tumor. In the present study, we employed eight RMS cell lines (three fusion positive and five fusion negative RMS cell lines) and mRNA samples obtained from RMS patients. The expression of sex hormone receptors was evaluated by RT-PCR and their functionality by chemotaxis, adhesion and direct cell proliferation assays. We report here for the first time that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) receptors are expressed in established human RMS cell lines as well as in primary tumor samples isolated from RMS patients. We also report that human RMS cell lines responded both to pituitary and gonadal sex hormone stimulation by enhanced proliferation, chemotaxis, cell adhesion and phosphorylation of MAPKp42/44 and AKT. In summary, our results indicate that sex hormones are involved in the pathogenesis and progression of RMS, and therefore, their therapeutic application should be avoided in patients that have been diagnosed with RMS. PMID:26983595

  8. Progress on the paternal brain: theory, animal models, human brain research, and mental health implications.

    Science.gov (United States)

    Swain, J E; Dayton, C J; Kim, P; Tolman, R M; Volling, B L

    2014-01-01

    With a secure foundation in basic research across mammalian species in which fathers participate in the raising of young, novel brain-imaging approaches are outlining a set of consistent brain circuits that regulate paternal thoughts and behaviors in humans. The newest experimental paradigms include increasingly realistic baby-stimuli to provoke paternal cognitions and behaviors with coordinated hormone measures to outline brain networks that regulate motivation, reflexive caring, emotion regulation, and social brain networks with differences and similarities to those found in mothers. In this article, on the father brain, we review all brain-imaging studies on PubMed to date on the human father brain and introduce the topic with a selection of theoretical models and foundational neurohormonal research on animal models in support of the human work. We discuss potentially translatable models for the identification and treatment of paternal mood and father-child relational problems, which could improve infant mental health and developmental trajectories with potentially broad public health importance. © 2014 Michigan Association for Infant Mental Health.

  9. The origins of genetic variation between individual human oocytes and embryos: implications for infertility.

    Science.gov (United States)

    Delhanty, Joy D A

    2013-12-01

    Human fertility is low in comparison with that seen in other well-studied mammals. The main reason for this state of affairs seems to be the frequent occurrence and persistence of chromosomal errors in the human conceptus. Evidence obtained over the past two decades shows that the exceptionally high incidence of chromosomal anomalies seen in human preimplantation embryos is the result of errors that may occur at various stages during gamete and embryo formation. In rare cases, an error may exist or arise in the premeiotic germ cells; much more commonly it may arise during the first or second meiotic division in the male or female. Highly efficient cell cycle checkpoints in the male ensure that the incidence of aneuploidy in mature sperm is low compared to that in the oocyte. Most 3-day-old embryos created by IVF are chromosomal mosaics, and this persists to a lesser degree to the blastocyst stage on day 5. While aneuploidy of meiotic origin is a major factor affecting the fertility of older women, embryos from most younger women will have predominantly post-zygotic mitotic errors. Couples experiencing RIF are particularly likely to produce highly abnormal (chaotic) embryos by post-zygotic mechanisms.

  10. Human Expeditions to Near-Earth Asteroids: Implications for Exploration, Resource Utilization, Science, and Planetary Defense

    Science.gov (United States)

    Abell, Paul; Mazanek, Dan; Barbee, Brent; Landis, Rob; Johnson, Lindley; Yeomans, Don; Friedensen, Victoria

    2013-01-01

    Over the past several years, much attention has been focused on human exploration of near-Earth asteroids (NEAs) and planetary defence. Two independent NASA studies examined the feasibility of sending piloted missions to NEAs, and in 2009, the Augustine Commission identified NEAs as high profile destinations for human exploration missions beyond the Earth-Moon system as part of the Flexible Path. More recently the current U.S. presidential administration directed NASA to include NEAs as destinations for future human exploration with the goal of sending astronauts to a NEA in the mid to late 2020s. This directive became part of the official National Space Policy of the United States of America as of June 28, 2010. With respect to planetary defence, in 2005 the U.S. Congress directed NASA to implement a survey program to detect, track, and characterize NEAs equal or greater than 140 m in diameter in order to access the threat from such objects to the Earth. The current goal of this survey is to achieve 90% completion of objects equal or greater than 140 m in diameter by 2020.

  11. Amino acid composition analysis of human secondary transport proteins and implications for reliable membrane topology prediction.

    Science.gov (United States)

    Saidijam, Massoud; Azizpour, Sonia; Patching, Simon G

    2016-07-08

    Secondary transporters in humans are a large group of proteins that transport a wide range of ions, metals, organic and inorganic solutes involved in energy transduction, control of membrane potential and osmotic balance, metabolic processes and in the absorption or efflux of drugs and xenobiotics. They are also emerging as important targets for development of new drugs and as target sites for drug delivery to specific organs or tissues. We have performed amino acid composition (AAC) and phylogenetic analyses and membrane topology predictions for 336 human secondary transport proteins and used the results to confirm protein classification and to look for trends and correlations with structural domains and specific substrates and/or function. Some proteins showed statistically high contents of individual amino acids or of groups of amino acids with similar physicochemical properties. One recurring trend was a correlation between high contents of charged and/or polar residues with misleading results in predictions of membrane topology, which was especially prevalent in Mitochondrial Carrier family proteins. We demonstrate how charged or polar residues located in the middle of transmembrane helices can interfere with their identification by membrane topology tools resulting in missed helices in the prediction. Comparison of AAC in the human proteins with that in 235 secondary transport proteins from Escherichia coli revealed similar overall trends along with differences in average contents for some individual amino acids and groups of similar amino acids that are presumed to result from a greater number of functions and complexity in the higher organism.

  12. The Effects of Uniquely-Processed Titanium on Biological Systems: Implications for Human Health and Performance

    Directory of Open Access Journals (Sweden)

    David S. Rowlands

    2014-01-01

    Full Text Available Titanium is biocompatible and widely utilized in a variety of applications. Recently, titanium in pico-nanometer scale and soluble form (Aqua Titan has expanded its use to applied human health and performance. The purpose of this article is to review the current evidence associated with specific physiological responses to Aqua Titan-treated materials. In vitro studies have shown that application of Aqua Titan can modify membrane potential and long-term potentiation in isolated hippocampal neurons, suggesting reduced pain memory as a possible mechanism for reported analgesia. Proximal contact with Aqua Titan-treated titanium increased gene expression, protein synthesis, cell growth and adhesion in normal cultured muscle and bone cells, suggesting application for Aqua Titan in clinical implant procedures and wound healing. Evidence for beneficial effects on neuromuscular control of muscle-tendon function and improvements in running economy in human athletes was seen when Aqua Titan-treated tape was applied to the human triceps surae following fatigue induced by prior strenuous exercise. Finally, behavioral responses and effects on the autonomic nervous system to environmental exposure suggest Aqua Titan may promote a mild relaxant, or stress-suppressive response. Together, data suggest exposure to Aqua Titan-treated materials modulates aspects of growth and function in neuronal and other musculoskeletal cells with possible benefits to musculotendinous recovery from exercise and to the systemic response to stress.

  13. Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus-type I.

    Science.gov (United States)

    Yeaman, Grant R; Asin, Susana; Weldon, Sally; Demian, Douglas J; Collins, Jane E; Gonzalez, Jorge L; Wira, Charles R; Fanger, Michael W; Howell, Alexandra L

    2004-12-01

    Human immunodeficiency virus-type 1 (HIV-1) is a sexually transmitted pathogen that can infect cells in the female reproductive tract (FRT). The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not well understood. To characterize the frequency of potential targets of HIV infection within the FRT, we performed a systematic study of the expression of HIV receptors (CD4, galactosyl ceramide (GalCer)) and coreceptors (CXCR4 and CCR5) on epithelial cells and leucocytes from the ectocervix. The ectocervix is a likely first site of contact with HIV-1 following heterosexual transmission, and expression of these receptors is likely to correlate with susceptibility to viral infection. We obtained ectocervical tissue specimens from women undergoing hysterectomy, and compared expression of these receptors among patients who were classified as being in the proliferative or secretory phases of their menstrual cycle at the time of hysterectomy, as well as from postmenopausal tissues. Epithelial cells from tissues at early and mid-proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. These findings are important to define potential targets of HIV-1 infection within the FRT, and for the future design of approaches to reduce the susceptibility of women to infection by HIV-1.

  14. Structural insights into human angiogenin variants implicated in Parkinson’s disease and Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Bradshaw, William J.; Rehman, Saima; Pham, Tram T. K.; Thiyagarajan, Nethaji; Lee, Rebecca L.; Subramanian, Vasanta; Acharya, K. Ravi

    2017-01-01

    Mutations in Angiogenin (ANG), a member of the Ribonuclease A superfamily (also known as RNase 5) are known to be associated with Amyotrophic Lateral Sclerosis (ALS, motor neurone disease) (sporadic and familial) and Parkinson’s Disease (PD). In our previous studies we have shown that ANG is expressed in neurons during neuro-ectodermal differentiation, and that it has both neurotrophic and neuroprotective functions. In addition, in an extensive study on selective ANG-ALS variants we correlated the structural changes to the effects on neuronal survival and the ability to induce stress granules in neuronal cell lines. Furthermore, we have established that ANG-ALS variants which affect the structure of the catalytic site and either decrease or increase the RNase activity affect neuronal survival. Neuronal cell lines expressing the ANG-ALS variants also lack the ability to form stress granules. Here, we report a detailed experimental structural study on eleven new ANG-PD/ALS variants which will have implications in understanding the molecular basis underlying their role in PD and ALS. PMID:28176817

  15. Implications of an animal model of sugar addiction, withdrawal and relapse for human health.

    Science.gov (United States)

    Wideman, C H; Nadzam, G R; Murphy, H M

    2005-01-01

    The effect of intermittent glucose administration on the circadian rhythm of body temperature was studied in rats to provide evidence of sugar addiction, withdrawal and relapse. Metabolic and behavioral phenomena were also observed. Biotelemetry transmitters recorded body temperature for the duration of the 4-week experiment. Rats were divided into an experimental and a control group, which were maintained on the same habituation conditions for the duration of the experiment, with the exception of weeks 2 and 4, when the experimental group was presented with a 25% glucose solution. Experimental animals displayed a precipitous drop in body temperature and behavioral changes associated with withdrawal during week 3, when sugar was removed. There was an increase in kilocalories (kcal) consumed during weeks 2 and 4 by experimental animals and, by the end of the experiment, these animals showed a greater percent increase in body weight. Elevated blood glucose levels were found in experimental animals. The study demonstrates that the effects of sugar addiction, withdrawal and relapse are similar to those of drugs of abuse. Implications of the rewarding and addicting effects of sugar are related to weight gain, obesity and Type II diabetes. Furthermore, pitfalls related to dieting are elucidated.

  16. Implication of a protein-tyrosine-phosphatase in human lung cancer.

    Science.gov (United States)

    Gaits, F; Li, R Y; Ragab, A; Selves, J; Ragab-Thomas, J M; Chap, H

    1994-07-01

    Protein tyrosyl phosphorylation plays an essential role in regulating cellular events such as proliferation, differentiation and oncogenesis. The recent characterization of the family of protein tyrosine phosphatases (PTPases) suggests that dephosphorylation might be a crucial event in these phenomena. One of the functions of PTPases is to reverse the effect of protein tyrosine kinases (PTKases), many of which are oncogenes, suggesting that they may act as tumor suppressors as described for HPTP gamma. In order to investigate the implication in lung cancer of HPTP beta, a receptor PTPase, we have developed a semi-quantitative method derived from primer-directed reverse transcription (RT) and subsequent polymerase chain reaction (PCR) with 32P-labelled nucleotide. We have demonstrated that the expression of HPTP beta mRNA was dramatically decreased in lung adenocarcinomas and lung malpighian carcinomas as compared to normal lung tissue. In addition, HPTP beta was not expressed in the pulmonar adenocarcinoma cell line A427, which proliferates in a deregulated way. These results suggest that the loss of expression of HPTP beta might play a role in neoplasic transformation and thus this molecule could act as a tumor suppressor factor.

  17. Overshadowing and latent inhibition in nausea-based context conditioning in humans: Theoretical and practical implications.

    Science.gov (United States)

    Hall, Geoffrey; Stockhorst, Ursula; Enck, Paul; Klosterhalfen, Sibylle

    2016-01-01

    Volunteer participants underwent nausea-inducing body rotation in a distinctive context, and the acquired ability of the contextual cues to evoke nausea was subsequently assessed by a symptom rating scale. One group received prior exposure to the context (a latent inhibition procedure); a second consumed a novel flavour prior to rotation (an overshadowing procedure); a third group experienced both procedures; and a control group received neither. When tested in the context in the absence of rotation, all groups reported an increase in nausea-related symptoms at the time when rotation had previously occurred, an outcome consistent with the occurrence of conditioned nausea. The magnitude of this increase did not differ across the groups, but the overall level of responsiveness (the degree to which nausea-related symptoms were reported) was enhanced in the latent inhibition and reduced in the overshadowing condition. Cortisol levels showed the same pattern. The implications of these findings for the proposal that overshadowing and latent inhibition procedures might be used to control the development of anticipatory nausea in patients undergoing chemotherapy is considered.

  18. The Pasteur effect in human platelets: implications for storage and metabolic control.

    Science.gov (United States)

    Guppy, M; Abas, L; Arthur, P G; Whisson, M E

    1995-11-01

    The Pasteur effect and the associated acidosis have long been considered a major cause of platelet death during storage. We have investigated this phenomenon using a defined platelet preparation and a system whereby the oxidative and glycolytic contributions to total ATP production can be measured over a range of oxygen concentrations from saturating (pO2 = 158 mmHg) to anoxic (pO2 = 0 mmHg). Platelets do not show a Pasteur effect until the pO2 decreases to Pasteur effect is therefore not a likely cause of platelet death during storage where pO2 in a storage bag typically drops to no less than 50 mmHg. The data also have implications for the role of oxygen diffusion in oxidative metabolism, and for the compensatory nature of the Pasteur effect. As platelets are relatively small cells, and the onset of the Pasteur effect occurs at a relatively low oxygen concentration, diffusion may limit the rate of oxygen consumption in most other (larger) cells. The Pasteur effect is only fully compensative if the P/O2 ratio used for the calculations is lower than the conventional one. Since recent research strongly suggests that the conventional P/O2 ratio is too high, examples of fully compensative Pasteur effects may be more common than the literature suggests.

  19. Implications of prion adaptation and evolution paradigm for human neurodegenerative diseases.

    Science.gov (United States)

    Kabir, M Enamul; Safar, Jiri G

    2014-01-01

    There is a growing body of evidence indicating that number of human neurodegenerative diseases, including Alzheimer disease, Parkinson disease, fronto-temporal dementias, and amyotrophic lateral sclerosis, propagate in the brain via prion-like intercellular induction of protein misfolding. Prions cause lethal neurodegenerative diseases in humans, the most prevalent being sporadic Creutzfeldt-Jakob disease (sCJD); they self-replicate and spread by converting the cellular form of prion protein (PrP(C)) to a misfolded pathogenic conformer (PrP(Sc)). The extensive phenotypic heterogeneity of human prion diseases is determined by polymorphisms in the prion protein gene, and by prion strain-specific conformation of PrP(Sc). Remarkably, even though informative nucleic acid is absent, prions may undergo rapid adaptation and evolution in cloned cells and upon crossing the species barrier. In the course of our investigation of this process, we isolated distinct populations of PrP(Sc) particles that frequently co-exist in sCJD. The human prion particles replicate independently and undergo competitive selection of those with lower initial conformational stability. Exposed to mutant substrate, the winning PrP(Sc) conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to the lowest stability. Thus, the evolution and adaptation of human prions is enabled by a dynamic collection of distinct populations of particles, whose evolution is governed by the selection of progressively less stable, faster replicating PrP(Sc) conformers. This fundamental biological mechanism may explain the drug resistance that some prions gained after exposure to compounds targeting PrP(Sc). Whether the phenotypic heterogeneity of other neurodegenerative diseases caused by protein misfolding is determined by the spectrum of misfolded conformers (strains) remains to be established. However, the prospect that these conformers may evolve and

  20. Sexual Risk Behaviors Constructed in Iranian Women's Life with Substance Use Disorders: A New Implication of Human Ecological Theory.

    Science.gov (United States)

    Jamshidimanesh, Mansoureh; Mousavi, Seyed Abbas; Merghati-Khoei, Effat; Emamian, Mohammad Hassan; Keramat, Afsaneh

    2016-07-01

    Drug abuse is one of the important variables influencing protective sexual behavior. The objective of this study was to explore how risky sexual behaviors develop in drug abusing women using human ecological theory. In this study, we used a descriptive exploratory approach. The participants were 32 drug abusing women from two of the selected drop-in centers (DICs) in south Tehran, Iran, where we could have access to a vast number of female drug users. Data was collected using semi-structured face-to-face interviews. Qualitative content analysis was used to analyze the data using Graneheim and Lundman procedure. Risky sexual behavior in drug use disorders in women was found in four themes with thirteen emerged; sexual untaught at micro-system with two subthemes "unsafe home" and "drop out of school", Perception of differences at meso-system with three subthemes "lack of link between family and school", "doing manly behavior" and "low awareness of health puberty than peers", inappropriate marriages at exo-system with three subthemes "stigma", "fear of losing love relationship" and "self-devotion", marginalization at macro-system with four subthemes "barrier access to rights", "selling sex as a tool of security", "lack of belief as a sex worker" and "mistrust and doubt partner" using implication of human ecological theory. Findings suggest that strategies supporting the discovery of risky sexual behaviors in drug use disorders in women are important in order to provide counseling and education to form their decisions toward safety sex.

  1. In vitro fertilization (IVF) in mammals: epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans.

    Science.gov (United States)

    Ventura-Juncá, Patricio; Irarrázaval, Isabel; Rolle, Augusto J; Gutiérrez, Juan I; Moreno, Ricardo D; Santos, Manuel J

    2015-12-18

    The advent of in vitro fertilization (IVF) in animals and humans implies an extraordinary change in the environment where the beginning of a new organism takes place. In mammals fertilization occurs in the maternal oviduct, where there are unique conditions for guaranteeing the encounter of the gametes and the first stages of development of the embryo and thus its future. During this period a major epigenetic reprogramming takes place that is crucial for the normal fate of the embryo. This epigenetic reprogramming is very vulnerable to changes in environmental conditions such as the ones implied in IVF, including in vitro culture, nutrition, light, temperature, oxygen tension, embryo-maternal signaling, and the general absence of protection against foreign elements that could affect the stability of this process. The objective of this review is to update the impact of the various conditions inherent in the use of IVF on the epigenetic profile and outcomes of mammalian embryos, including superovulation, IVF technique, embryo culture and manipulation and absence of embryo-maternal signaling. It also covers the possible transgenerational inheritance of the epigenetic alterations associated with assisted reproductive technologies (ART), including its phenotypic consequences as is in the case of the large offspring syndrome (LOS). Finally, the important scientific and bioethical implications of the results found in animals are discussed in terms of the ART in humans.

  2. Ecohydrology across Scales in an Arid, Human-dominated Landscape: Implications for Ecosystems, Water Availability and Human Interactions

    Science.gov (United States)

    Belnap, J.; Deems, J. S.; Kind, A.; Munson, S.; Neff, J.; Okin, G.; Painter, T. H.; Reheis, M. C.; Reynolds, R. L.; Wilcox, B. P.

    2011-12-01

    Arid and semi-arid regions constitute over 35% of global lands. The utilization of these areas is increasing rapidly in response to rising human populations and attendant food needs. In addition, they are also foci for activities associated with energy production, mineral extraction, military training and conflict, and recreation. The resultant disturbance reduces the protective cover of plants and physical and biological soil crusts. This leads to accelerated soil loss by both wind and water, across a wide range of parent materials, textures, or soil surface ages. Further vulnerability to soil erosion is expected with predicted future drier and hotter climates, as plant cover declines and fires increase. Synergistic effects, such as surface disturbance occurring during drought periods in plant communities dominated by annual weeds, can exacerbate the situation further. At a local scale, the redistribution of soil by wind and water results in nutrients being more heterogeneously distributed, subsequently altering abundance and distribution of plants, animals, and rates of biogeochemical cycling. Particles transported by wind from disturbed settings can be deposited in washes, subsequently entering streams and rivers.Particles saltating across the soil surface are also frequently deposited in washes, subsequently entering streams and rivers. This process represents a local loss of soil fertility and a local and regional decrease in water quality, as sediment and salts enter water bodies. At the larger watershed scale, dust is deposited on nearby snow cover, darkening the snow and increasing melt rates. Increased melt rates decrease the length of the snow-cover season, increasing water losses to evapotranspiration and thus the amount of water entering streams and rivers. As water quantity decreases, salts and sediments are concentrated, thereby further decreasing water quality. As water becomes scarcer in drylands around the world, the diminishing integrity of the

  3. Nuclear localization of human spermine oxidase isoforms - possible implications in drug response and disease etiology.

    Science.gov (United States)

    Murray-Stewart, Tracy; Wang, Yanlin; Goodwin, Andrew; Hacker, Amy; Meeker, Alan; Casero, Robert A

    2008-06-01

    The recent discovery of the direct oxidation of spermine via spermine oxidase (SMO) as a mechanism through which specific antitumor polyamine analogues exert their cytotoxic effects has fueled interest in the study of the polyamine catabolic pathway. A major byproduct of spermine oxidation is H2O2, a source of toxic reactive oxygen species. Recent targeted small interfering RNA studies have confirmed that SMO-produced reactive oxygen species are directly responsible for oxidative stress capable of inducing apoptosis and potentially mutagenic DNA damage. In the present study, we describe a second catalytically active splice variant protein of the human spermine oxidase gene, designated SMO5, which exhibits substrate specificities and affinities comparable to those of the originally identified human spermine oxidase-1, SMO/PAOh1, and, as such, is an additional source of H2O2. Importantly, overexpression of either of these SMO isoforms in NCI-H157 human non-small cell lung carcinoma cells resulted in significant localization of SMO protein in the nucleus, as determined by confocal microscopy. Furthermore, cell lines overexpressing either SMO/PAOh1 or SMO5 demonstrated increased spermine oxidation in the nucleus, with accompanying alterations in individual nuclear polyamine concentrations. This increased oxidation of spermine in the nucleus therefore increases the production of highly reactive H2O2 in close proximity to DNA, as well as decreases nuclear spermine levels, thus altering the protective roles of spermine in free radical scavenging and DNA shielding, and resulting in an overall increased potential for oxidative DNA damage in these cells. The results of these studies therefore have considerable significance both with respect to targeting polyamine oxidation as an antineoplastic strategy, and in regard to the potential role of spermine oxidase in inflammation-induced carcinogenesis.

  4. The time-delayed inverted pendulum: Implications for human balance control

    Science.gov (United States)

    Milton, John; Cabrera, Juan Luis; Ohira, Toru; Tajima, Shigeru; Tonosaki, Yukinori; Eurich, Christian W.; Campbell, Sue Ann

    2009-06-01

    The inverted pendulum is frequently used as a starting point for discussions of how human balance is maintained during standing and locomotion. Here we examine three experimental paradigms of time-delayed balance control: (1) mechanical inverted time-delayed pendulum, (2) stick balancing at the fingertip, and (3) human postural sway during quiet standing. Measurements of the transfer function (mechanical stick balancing) and the two-point correlation function (Hurst exponent) for the movements of the fingertip (real stick balancing) and the fluctuations in the center of pressure (postural sway) demonstrate that the upright fixed point is unstable in all three paradigms. These observations imply that the balanced state represents a more complex and bounded time-dependent state than a fixed-point attractor. Although mathematical models indicate that a sufficient condition for instability is for the time delay to make a corrective movement, τn, be greater than a critical delay τc that is proportional to the length of the pendulum, this condition is satisfied only in the case of human stick balancing at the fingertip. Thus it is suggested that a common cause of instability in all three paradigms stems from the difficulty of controlling both the angle of the inverted pendulum and the position of the controller simultaneously using time-delayed feedback. Considerations of the problematic nature of control in the presence of delay and random perturbations ("noise") suggest that neural control for the upright position likely resembles an adaptive-type controller in which the displacement angle is allowed to drift for small displacements with active corrections made only when θ exceeds a threshold. This mechanism draws attention to an overlooked type of passive control that arises from the interplay between retarded variables and noise.

  5. Combined Proteome and Eicosanoid Profiling Approach for Revealing Implications of Human Fibroblasts in Chronic Inflammation.

    Science.gov (United States)

    Tahir, Ammar; Bileck, Andrea; Muqaku, Besnik; Niederstaetter, Laura; Kreutz, Dominique; Mayer, Rupert L; Wolrab, Denise; Meier, Samuel M; Slany, Astrid; Gerner, Christopher

    2017-02-07

    During inflammation, proteins and lipids act in a concerted fashion, calling for combined analyses. Fibroblasts are powerful mediators of chronic inflammation. However, little is known about eicosanoid formation by human fibroblasts. The aim of this study was to analyze the formation of the most relevant inflammation mediators including proteins and lipids in human fibroblasts upon inflammatory stimulation and subsequent treatment with dexamethasone, a powerful antiphlogistic drug. Label-free quantification was applied for proteome profiling, while an in-house established data-dependent analysis method based on high-resolution mass spectrometry was applied for eicosadomics. Furthermore, a set of 188 metabolites was determined by targeted analysis. The secretion of 40 proteins including cytokines, proteases, and other inflammation agonists as well as 14 proinflammatory and nine anti-inflammatory eicosanoids was found significantly induced, while several acylcarnithins and sphingomyelins were found significantly downregulated upon inflammatory stimulation. Treatment with dexamethasone downregulated most cytokines and proteases, abrogated the formation of pro- but also anti-inflammatory eicosanoids, and restored normal levels of acylcarnithins but not of sphingomyelins. In addition, the chemokines CXCL1, CXCL5, CXCL6, and complement C3, known to contribute to chronic inflammation, were not counter-regulated by dexamethasone. Similar findings were obtained with human mesenchymal stem cells, and results were confirmed by targeted analysis with multiple reaction monitoring. Comparative proteome profiling regarding other cells demonstrated cell-type-specific synthesis of, among others, eicosanoid-forming enzymes as well as relevant transcription factors, allowing us to better understand cell-type-specific regulation of inflammation mediators and shedding new light on the role of fibroblasts in chronic inflammation.

  6. Traffic signatures in suspended dust at pedestrian levels in semiarid zones: Implications for human exposure

    Science.gov (United States)

    Meza-Figueroa, Diana; González-Grijalva, Belem; Del Río-Salas, Rafael; Coimbra, Rute; Ochoa-Landin, Lucas; Moreno-Rodríguez, Verónica

    2016-08-01

    Deeper knowledge on dust suspension processes along semiarid zones is critical for understanding potential impacts on human health. Hermosillo city, located in the heart of the Sonoran Desert was chosen to evaluate such impacts. A one-year survey of Total Suspended Particulate Matter (TSPM) was conducted at two different heights (pedestrian and rooftop level). The minimum values of TSPM were reported during monsoon season and winter. Maximum values showed a bimodal distribution, with major peaks associated with increase and decrease of temperature, as well as decreasing humidity. Concentrations of TSPM were significantly exceeded at pedestrian level (∼44% of analyzed days) when compared to roof level (∼18% of analyzed days). Metal concentrations of As, Pb, Cu, Sb, Be, Mg, Ni, and Co were higher at pedestrian level than at roof level. Pixel counting and interpretations based on scanning electron microscopy of dust filters showed a higher percentage of fine particulate fractions at pedestrian level. These fractions occur mainly as metal-enriched agglomerates resembling coarser particles. According to worldwide guidelines, particulate matter sampling should be conducted by monitoring particle sizes equal and inferior to PM10. However, this work suggests that such procedures may compromise risk assessment in semiarid environments, where coarse particles act as main carriers for emergent contaminants related to traffic. This effect is especially concerning at pedestrian level, leading to an underestimation of potential impacts of human exposure. This study brings forward novel aspects that are of relevance for those concerned with dust suspension processes across semiarid regions and related impact on human health.

  7. Mechanisms of Human Sensorimotor-Learning and Their Implications for Brain Communication

    Science.gov (United States)

    Imamizu, Hiroshi

    Humans have a remarkable ability to flexibly control various objects such as tools. Much evidence suggests that the internal models acquired in the central nervous system (CNS) support flexible control. Internal models are neural mechanisms that mimic the input-output properties of controlled objects. In a series of functional magnetic resonance imaging (fMRI) studies, we demonstrate how the CNS acquires and switches internal models for dexterous use of many tools. In the first study, we investigated human cerebellar activity when human subjects learned how to use a novel tool (a rotated computer mouse, where the cursor appears in a rotated position) and found that activity reflecting an internal model of the novel tool increases in the lateral cerebellum after learning how to use the tool. In the second study, we investigated the internal-model activity after sufficient training in the use of two types of novel tools (the rotated mouse and a velocity mouse, where the cursor's velocity is proportional to mouse's position) and found that the cerebellar activities for the two tools were spatially segregated. In the third study, we investigated brain activity associated with the flexible switching of tools. We found that the activity related to switching internal models was in the prefrontal lobe (area 46 and the insula), the parietal lobe, and the cerebellum. These results suggest that internal models in the cerebellum represent input-output properties of the tools as modulators of continuous signals. The cerebellar abilities in adaptive modulation of signals can be used to enhance the control signals in communications between the brain and computers.

  8. NADPH-diaphorase-positive neurons in the human inferior colliculus: morphology, distribution and clinical implications.

    Science.gov (United States)

    Hinova-Palova, D; Landzhov, B; Dzhambazova, E; Edelstein, L; Minkov, M; Fakih, K; Minkov, R; Paloff, A; Ovtscharoff, W

    2017-05-01

    Using the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reaction with nitroblue tetrazolium, we provided a detailed investigation of the distribution, dimensional characteristics and morphology of NADPH-d-positive neurons in the three main subdivisions of the human inferior colliculus (IC): central nucleus, pericentral nucleus, and external nucleus. In accordance with their perikaryal diameter, dendritic and axonal morphology, these neurons were categorized as large (averaging up to 45 μm in diameter), medium (20-30 µm), small (13-16 µm) and very small (7-10 µm). Their morphological differences could contribute to varying functionality and processing capacity. Our results support the hypothesis that large and medium NADPH-d-positive cells represent projection neurons, while the small cells correspond to interneurons. Heretofore, the very small NADPH-d-positive neurons have not been described in any species. Their functions-and if they are, indeed, the smallest neurons in the IC of humans-remain to be clarified. Owing to their location, we posit that they are interneurons that connect the large NADPH-d-positive neurons and thereby serve as an anatomical substrate for information exchange and processing before feeding forward to higher brain centers. Our results also suggest that the broad distribution of nitric oxide (NO) synthesis in the human IC is closely tied to the neuromodulatory action of NO on collicular neurotransmitters such as GABA and glutamate, and to calcium-binding proteins such as parvalbumin. A deeper understanding of the relationship between NADPH-d-positive fibers in all IC connections and their co-localization with other neurotransmitters and calcium-binding proteins will assist in better defining the function of NO in the context of its interplay with the cerebral cortex, the sequelae of the aging process and neurodegenerative disorders.

  9. Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells

    Directory of Open Access Journals (Sweden)

    Buqué Aitziber

    2012-04-01

    Full Text Available Abstract Background Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC, and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet. Results In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and –independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis. Conclusions We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and –independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.

  10. ELSI Bibliography: Ethical legal and social implications of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Yesley, M.S. [comp.

    1993-11-01

    This second edition of the ELSI Bibliography provides a current and comprehensive resource for identifying publications on the major topics related to the ethical, legal and social issues (ELSI) of the Human Genome Project. Since the first edition of the ELSI Bibliography was printed last year, new publications and earlier ones identified by additional searching have doubled our computer database of ELSI publications to over 5600 entries. The second edition of the ELSI Bibliography reflects this growth of the underlying computer database. Researchers should note that an extensive collection of publications in the database is available for public use at the General Law Library of Los Alamos National Laboratory (LANL).

  11. Recombinant human erythropoietin, and myocardial and cerebral acute ischemia: implications for clinical use.

    Directory of Open Access Journals (Sweden)

    Rafael Alejandro Gómez Baute

    2010-07-01

    Full Text Available Recombinant human erythropoietin has been used for more than two decades in clinical practice with promising results in the treatment of anemia associated with chronic renal insufficiency and in patients with cancer. Recent evidence has uncovered new nonhematopoietic functions of this protein and have brought new hope in the treatment of diseases with ischemic component. In the present review is rife with detail about these new features in the light of new discoveries and explores the therapeutic opportunities offered by these new scientific evidence.

  12. Economy-wide estimates of the implications of climate change. Human health

    Energy Technology Data Exchange (ETDEWEB)

    Bosello, Francesco [Fondazione Eni Enrico Mattei, Venice (Italy); Roson, Roberto [International Centre for Theoretical Physics, Trieste (Italy); Tol, Richard S.J. [Centre for Marine and Climate Research, Hamburg University, Hamburg (Germany)

    2006-06-25

    We study the economic impacts of climate-change-induced change in human health, viz. cardiovascular and respiratory disorders, diarrhoea, malaria, dengue fever and schistosomiasis. Changes in morbidity and mortality are interpreted as changes in labour productivity and demand for health care, and used to shock the GTAP-E computable general equilibrium model, calibrated for the year 2050. GDP, welfare and investment fall (rise) in regions with net negative (positive) health impacts. Prices, production, and terms of trade show a mixed pattern. Direct cost estimates, common in climate change impact studies, underestimate the true welfare losses. (author)

  13. Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing.

    Science.gov (United States)

    Koob, Thomas J; Rennert, Robert; Zabek, Nicole; Massee, Michelle; Lim, Jeremy J; Temenoff, Johnna S; Li, William W; Gurtner, Geoffrey

    2013-10-01

    Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests

  14. Myopia, intelligence, and the expanding human neocortex: behavioral influences and evolutionary implications.

    Science.gov (United States)

    Storfer, M

    1999-06-01

    The first two parts of this monograph document that areas of the human neocortex heavily used to cope with a complex, language-driven society have been expanding rapidly and suggest strongly that this is linked with the huge upsurge that's occurred in myopia, and with the large gradual 20th-century increase in measured intelligence. Part III proposes mechanisms capable of supporting such rapid changes, without violating the basic precepts of Darwin's thinking. Part IV discusses the social and evolutionary ramifications of our apparent proclivity for rapid, progressive, adaptive neocortical change, and suggests areas for productive research.

  15. Abuse, Neglect, and Violence Against Elderly Women in Ghana: Implications for Social Justice and Human Rights.

    Science.gov (United States)

    Sossou, Marie-Antoinette; Yogtiba, Joseph A

    2015-01-01

    This article discusses abuse and neglect of elderly women in Ghana and the traditional practices that adversely affect their human rights. Their situation is characterized by pervasive poverty, illiteracy, widowhood, predominantly rural dwelling, and subjection to insidious cultural practices and superstitious beliefs. Increase in life expectancy and population trends point to significant increases in the numbers of the elderly women. Breakdown of the extended family support system and the waning of filial obligations are factors affecting their welfare. Accurate data on these abuses is lacking due to cultural inhibitions and non-reporting. Legislations and NGO programs are addressed to combat abuses.

  16. Changing air mass frequencies in Canada: potential links and implications for human health.

    Science.gov (United States)

    Vanos, J K; Cakmak, S

    2014-03-01

    Many individual variables have been studied to understand climate change, yet an overall weather situation involves the consideration of many meteorological variables simultaneously at various times diurnally, seasonally, and yearly. The current study identifies a full weather situation as an air mass type using synoptic scale classification, in 30 population centres throughout Canada. Investigative analysis of long-term air mass frequency trends was completed, drawing comparisons between seasons and climate zones. We find that the changing air mass trends are highly dependent on the season and climate zone being studied, with an overall increase of moderate ('warm') air masses and decrease of polar ('cold') air masses. In the summertime, general increased moisture content is present throughout Canada, consistent with the warming air masses. The moist tropical air mass, containing the most hot and humid air, is found to increase in a statistically significant fashion in the summertime in 46% of the areas studied, which encompass six of Canada's ten largest population centres. This emphasises the need for heat adaptation and acclimatisation for a large proportion of the Canadian population. In addition, strong and significant decreases of transition/frontal passage days were found throughout Canada. This result is one of the most remarkable transition frequency results published to date due to its consistency in identifying declining trends, coinciding with research completed in the United States (US). We discuss relative results and implications to similar US air mass trend analyses, and draw upon research studies involving large-scale upper-level air flow and vortex connections to air mass changes, to small-scale meteorological and air pollution interactions. Further research is warranted to better understand such connections, and how these air masses relate to the overall and city-specific health of Canadians.

  17. Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure

    Science.gov (United States)

    Millucci, Lia; Paccagnini, Eugenio; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Laschi, Marcella; Consumi, Marco; Spreafico, Adriano; Tanganelli, Piero; Lupetti, Pietro; Magnani, Agnese; Santucci, Annalisa

    2011-01-01

    Aims Atrial Natriuretic Peptide (ANP)-containing amyloid is frequently found in the elderly heart. No data exist regarding ANP aggregation process and its link to pathologies. Our aims were: i) to experimentally prove the presumptive association of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby elucidating IAA implication in the CHF pathogenesis. Methods and Results A significant prevalence (85%) of IAA was immunohistochemically proven ex vivo in biopsies from CHF patients. We investigated in vitro (using Congo Red, Thioflavin T, SDS-PAGE, transmission electron microscopy, infrared spectroscopy) ANP fibrillogenesis, starting from α-ANP as well as the ability of dimeric β-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing β-ANP prevalence in CHF. Our results defined the uncommon rapidity of α-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the onset of a fibrillization process subsequently proceeding at physiological pH. Interestingly, CHF-like conditions induced the production of the most stable and time-resistant ANP fibrils suggesting that CHF affected people may be prone to develop IAA. Conclusions We established a link between IAA and CHF by ex vivo examination and assessed that β-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that β-ANP plays a crucial role in ANP amyloid deposition under physiopathological CHF conditions. Overall, our findings indicate that early IAA-related ANP deposition may occur in CHF and suggest that these latter patients should be monitored for the development of cardiac amyloidosis. PMID:21814559

  18. Fat content, energy value and fatty acid profile of donkey milk during lactation and implications for human nutrition

    Directory of Open Access Journals (Sweden)

    Martemucci Giovanni

    2012-09-01

    Full Text Available Abstract Background and aims Milk contains numerous nutrients. The content of n-3 fatty acids, the n-6/n-3 ratio, and short- and medium-chain fatty acids may promote positive health effects. In Western societies, cow’s milk fat is perceived as a risk factor for health because it is a source of a high fraction of saturated fatty acids. Recently, there has been increasing interest in donkey’s milk. In this work, the fat and energetic value and acidic composition of donkey’s milk, with reference to human nutrition, and their variations during lactation, were investigated. We also discuss the implications of the acidic profile of donkey’s milk on human nutrition. Methods Individual milk samples from lactating jennies were collected 15, 30, 45, 60, 90, 120, 150, 180 and 210days after foaling, for the analysis of fat, proteins and lactose, which was achieved using an infrared milk analyser, and fatty acids composition by gas chromatography. Results The donkey’s milk was characterised by low fat and energetic (1719.2kJ·kg-1 values, a high polyunsaturated fatty acids (PUFA content of mainly α-linolenic acid (ALA and linoleic acid (LA, a low n-6 to n-3 FA ratio or LA/ALA ratio, and advantageous values of atherogenic and thrombogenic indices. Among the minor PUFA, docosahesaenoic (DHA, eicosapentanoic (EPA, and arachidonic (AA acids were present in very small amounts ( The fatty acid patterns were affected by the lactation stage and showed a decrease (P Conclusions The high level of unsaturated/saturated fatty acids and PUFA-n3 content and the low n-6/n-3 ratio suggest the use of donkey’s milk as a functional food for human nutrition and its potential utilisation for infant nutrition as well as adult diets, particular for the elderly.

  19. An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism.

    Science.gov (United States)

    Garaulet, Marta; Ordovás, José M; Gómez-Abellán, Purificación; Martínez, Jose A; Madrid, Juan A

    2011-08-01

    Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n=6) were obtained from morbid obese women (BMI≥40 kg/m(2) ). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative-amplitude among genes (P30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue.

  20. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  1. Role of ATRX in chromatin structure and function: implications for chromosome instability and human disease.

    Science.gov (United States)

    De La Fuente, Rabindranath; Baumann, Claudia; Viveiros, Maria M

    2011-08-01

    Functional differentiation of chromatin structure is essential for the control of gene expression, nuclear architecture, and chromosome stability. Compelling evidence indicates that alterations in chromatin remodeling proteins play an important role in the pathogenesis of human disease. Among these, α-thalassemia mental retardation X-linked protein (ATRX) has recently emerged as a critical factor involved in heterochromatin formation at mammalian centromeres and telomeres as well as facultative heterochromatin on the murine inactive X chromosome. Mutations in human ATRX result in an X-linked neurodevelopmental condition with various degrees of gonadal dysgenesis (ATRX syndrome). Patients with ATRX syndrome may exhibit skewed X chromosome inactivation (XCI) patterns, and ATRX-deficient mice exhibit abnormal imprinted XCI in the trophoblast cell line. Non-random or skewed XCI can potentially affect both the onset and severity of X-linked disease. Notably, failure to establish epigenetic modifications associated with the inactive X chromosome (Xi) results in several conditions that exhibit genomic and chromosome instability such as fragile X syndrome as well as cancer development. Insight into the molecular mechanisms of ATRX function and its interacting partners in different tissues will no doubt contribute to our understanding of the pathogenesis of ATRX syndrome as well as the epigenetic origins of aneuploidy. In turn, this knowledge will be essential for the identification of novel drug targets and diagnostic tools for cancer progression as well as the therapeutic management of global epigenetic changes commonly associated with malignant neoplastic transformation.

  2. Gene identification using exon amplification on human chromosome 18q21: implications for bipolar disorder.

    Science.gov (United States)

    Chen, H; Huo, Y; Patel, S; Zhu, X; Swift-Scanlan, T; Reeves, R H; DePaulo, R; Ross, C A; McInnis, M G

    2000-09-01

    We previously reported linkage between bipolar disorder and a region on human chromosome (HC) 18q21. To identify genes in this region, exon trapping was performed on cosmids isolated from an HC18-specific cosmid library (LL18NC02) using 47 sequence tagged site (STS) markers from 18q21 as hybridization probes. A total of 285 unique sequences (exons) were obtained from 850 sequenced clones. Homology searching of the databases using NCBI's BLAST algorithms revealed that 31 exons have identity to known genes and/or ESTs, seven are identical to regions of finished genomic sequences in the 18q21 region, 20 have significant similarity (>30% sequence identity) to genes from human and/or other species, 19 were repetitive sequences, and 208 sequences (72%) are novel. Seventy per cent of the trapped sequences were predicted to be derived from genes using library screening and RT-PCR analyses. This represents an initial stage in characterizing genes in a susceptibility region for further study in bipolar disorder or other diseases that map to this region.

  3. Human Leukocyte Antigen-G Within the Male Reproductive System: Implications for Reproduction.

    Science.gov (United States)

    Hviid, Thomas Vauvert F

    2015-01-01

    In sexual reproduction in humans, a man has a clear interest in ensuring that the immune system of his female partner accepts the semi-allogenic fetus. Increasing attention has been given to soluble immunomodulatory molecules in the seminal fluid as one mechanism of ensuring this, possibly by "priming" the woman's immune system before conception and at conception. Recent studies have demonstrated the presence of the immunoregulatory and tolerance-inducible human leukocyte antigen (HLA)-G in the male reproductive organs. The expression of HLA-G in the blastocyst and by extravillous trophoblast cells in the placenta during pregnancy has been well described. Highly variable amounts of soluble HLA-G (sHLA-G) in seminal plasma from different men have been reported, and the concentration of sHLA-G is associated with HLA-G genotype. A first pilot study indicates that the level of sHLA-G in seminal plasma may even be associated with the chance of pregnancy in couples, where the male partner has reduced semen quality. More studies are needed to verify these preliminary findings.

  4. Effects of isolation and confinement on humans-implications for manned space explorations.

    Science.gov (United States)

    Pagel, J I; Choukèr, A

    2016-06-15

    Human psychology and physiology are significantly altered by isolation and confinement. In light of planned exploration class interplanetary missions, the related adverse effects on the human body need to be explored and defined as they have a large impact on a mission's success. Terrestrial space analogs offer an excellent controlled environment to study some of these stressors during a space mission in isolation without the complex environment of the International Space Station. Participants subjected to these space analog conditions can encounter typical symptoms ranging from neurocognitive changes, fatigue, misaligned circadian rhythm, sleep disorders, altered stress hormone levels, and immune modulatory changes. This review focuses on both the psychological and the physiological responses observed in participants of long-duration spaceflight analog studies, such as Mars500 or Antarctic winter-over. They provide important insight into similarities and differences encountered in each simulated setting. The identification of adverse effects from confinement allows not only the crew to better prepare for but also to design feasible countermeasures that will help support space travelers during exploration class missions in the future. Copyright © 2016 the American Physiological Society.

  5. Deregulation of the miRNAs Expression in Cervical Cancer: Human Papillomavirus Implications

    Directory of Open Access Journals (Sweden)

    Yazmín Gómez-Gómez

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small non coding RNAs of 18–25 nucleotides in length. The temporal or short-lived expression of the miRNAs modulates gene expression post transcriptionally. Studies have revealed that miRNAs deregulation correlates and is involved with the initiation and progression of human tumors. Cervical cancer (CC displays notably increased or decreased expression of a large number of cellular oncogenic or tumor suppressive miRNAs, respectively. However, understanding the potential role of miRNAs in CC is still limited. In CC, the high-risk human papillomaviruses (HR-HPVs infection can affect the miRNAs expression through oncoprotein E6 and E7 that contribute to viral pathogenesis, although other viral proteins might also be involved. This deregulation in the miRNAs expression has an important role in the hallmarks of CC. Interestingly, the miRNA expression profile in CC can discriminate between normal and tumor tissue and the extraordinary stability of miRNAs makes it suitable to serve as diagnostic and prognostic biomarkers of cancer. In this review, we will summarize the role of the HR-HPVs in miRNA expression, the role of miRNAs in the hallmarks of CC, and the use of miRNAs as potential prognostic biomarkers in CC.

  6. Medical Hydrogeology of Asian Deltas: Status of Groundwater Toxicants and Nutrients, and Implications for Human Health

    Directory of Open Access Journals (Sweden)

    Mohammad A. Hoque

    2015-12-01

    Full Text Available Drinking water, a fluid primarily for human hydration, is also a source of mineral nutrients. Groundwater, a drinking water source for more than 70% of inhabitants living in Asian deltas, has received much attention because of its naturally occurring arsenic, but the linkage of arsenic toxicity with other water constituents has not been studied. In addition, although nutrients are generally provided by food, in under developed rural settings, where people subsist on low nutrient diets, drinking-water-nutrients may supply quantities critical to human health thereby preventing diseases. Here, we show, using augmented datasets from three Asian deltas (Bengal, Mekong, and Red River, that the chemical content of groundwater is so substantial that in some areas individuals obtain up to 50% or more of the recommended daily intake (RDI of some nutrients (e.g., calcium, magnesium, iron from just two litres of drinking water. We also show some indications of a spatial association of groundwater nutrients and health outcome using demographic health data from Bangladesh. We therefore suggest that an understanding of the association of non-communicable disease and poor nutrition cannot be developed, particularly in areas with high levels of dissolved solids in water sources, without considering the contribution of drinking water to nutrient and mineral supply.

  7. Functional genomics of human brain development and implications for autism spectrum disorders.

    Science.gov (United States)

    Ziats, M N; Grosvenor, L P; Rennert, O M

    2015-10-27

    Transcription of the inherited DNA sequence into copies of messenger RNA is the most fundamental process by which the genome functions to guide development. Encoded sequence information, inherited epigenetic marks and environmental influences all converge at the level of mRNA gene expression to allow for cell-type-specific, tissue-specific, spatial and temporal patterns of expression. Thus, the transcriptome represents a complex interplay between inherited genomic structure, dynamic experiential demands and external signals. This property makes transcriptome studies uniquely positioned to provide insight into complex genetic-epigenetic-environmental processes such as human brain development, and disorders with non-Mendelian genetic etiologies such as autism spectrum disorders. In this review, we describe recent studies exploring the unique functional genomics profile of the human brain during neurodevelopment. We then highlight two emerging areas of research with great potential to increase our understanding of functional neurogenomics-non-coding RNA expression and gene interaction networks. Finally, we review previous functional genomics studies of autism spectrum disorder in this context, and discuss how investigations at the level of functional genomics are beginning to identify convergent molecular mechanisms underlying this genetically heterogeneous disorder.

  8. Phthalates in indoor dust in Kuwait: implications for non-dietary human exposure.

    Science.gov (United States)

    Gevao, B; Al-Ghadban, A N; Bahloul, M; Uddin, S; Zafar, J

    2013-04-01

    Phthalates are semivolatile organic compounds with a ubiquitous environmental distribution. Their presence in indoor environments is linked to their use in a variety of consumer products such as children's toys, cosmetics, food packaging, flexible PVC flooring among others. The goal of this study was to investigate the occurrence and concentration of phthalates in dust from homes in Kuwait and to assess non-dietary human exposure to these phthalates. Dust samples were randomly collected from 21 homes and analyzed for eight phthalates. The concentrations of total phthalates were log normally distributed and ranged from 470 to 7800 μg/g. Five phthalates [Di(2-ethylhexyl) phthalate (DEHP), Di-n-octyl phthalate (DnOP), Di-n-butyl phthalate (DBP), Benzyl butyl phthalate (BzBP), and Dicyclohexyl phthalate (DcHP)] were routinely detected. The major phthalate compound was DEHP at a geometric mean concentration of 1704 μg/g (median, 2256 μg/g) accounting for 92% of the total phthalates measured. Using the measured concentrations and estimates of dust ingestion rates for children and adults, estimated human non-dietary exposure based on median phthalate concentrations ranged from 938 ng/kg-bd/day for adults to 13362 ng/kg-bd/day for toddlers. The difference in exposure estimates between children and adults in this study supports previous reports that children are at greater risk from pollutants that accumulate indoors.

  9. Parent and halogenated polycyclic aromatic hydrocarbons in farmed cockroaches and implications for human exposure.

    Science.gov (United States)

    Sun, Jian-Lin; Wang, Yan-Bing; Zeng, Hui; Ni, Hong-Gang

    2015-01-01

    Medicinal insects have been widely used to cure human diseases for ages. Nevertheless, knowledge about the toxic chemicals accumulated in medicinal insects and their effects on human health was insufficient. In the present study, sixteen priority polycyclic aromatic hydrocarbons (PAHs) and nine halogenated PAHs (HPAHs) were determined in farmed medicinal cockroaches to address this issue. Total concentrations of PAHs in young nymphs, old nymphs, and adults ranged from 162 to 1025, 252 to 967, and 267 to 1168 ng/g, respectively. Levels of the sum of HPAHs varied from 0.84 to 9.17, 1.86 to 5.21, and 1.01 to 8.60 ng/g for young nymphs, old nymphs, and adults, respectively. The daily intake and excess cancer risk of PAHs and HPAHs were calculated for people who take cockroach-related drugs. Our results indicated that females and children have slightly higher exposure levels from the perspectives of gender and age, respectively. The estimated excess cancer risk of PAHs and HPAHs were both lower than the priority risk level (10(-4)), indicating a low potential carcinogenic risk with the medicinal cockroach consumption.

  10. Short and long-term energy intake patterns and their implications for human body weight regulation.

    Science.gov (United States)

    Chow, Carson C; Hall, Kevin D

    2014-07-01

    Adults consume millions of kilocalories over the course of a few years, but the typical weight gain amounts to only a few thousand kilocalories of stored energy. Furthermore, food intake is highly variable from day to day and yet body weight is remarkably stable. These facts have been used as evidence to support the hypothesis that human body weight is regulated by active control of food intake operating on both short and long time scales. Here, we demonstrate that active control of human food intake on short time scales is not required for body weight stability and that the current evidence for long term control of food intake is equivocal. To provide more data on this issue, we emphasize the urgent need for developing new methods for accurately measuring energy intake changes over long time scales. We propose that repeated body weight measurements can be used along with mathematical modeling to calculate long-term changes in energy intake and thereby quantify adherence to a diet intervention and provide dynamic feedback to individuals that seek to control their body weight.

  11. The Human Gut Phage Community and Its Implications for Health and Disease

    Science.gov (United States)

    Manrique, Pilar; Dills, Michael; Young, Mark J.

    2017-01-01

    In this review, we assess our current understanding of the role of bacteriophages infecting the human gut bacterial community in health and disease. In general, bacteriophages contribute to the structure of their microbial communities by driving host and viral diversification, bacterial evolution, and by expanding the functional diversity of ecosystems. Gut bacteriophages are an ensemble of unique and shared phages in individuals, which encompass temperate phages found predominately as prophage in gut bacteria (prophage reservoir) and lytic phages. In healthy individuals, only a small fraction of the prophage reservoir is activated and found as extracellular phages. Phage community dysbiosis is characterized by a shift in the activated prophage community or an increase of lytic phages, and has been correlated with disease, suggesting that a proper balance between lysis and lysogeny is needed to maintain health. Consequently, the concept of microbial dysbiosis might be extended to the phage component of the microbiome as well. Understanding the dynamics and mechanisms to restore balance after dysbiosis is an active area of research. The use of phage transplants to re-establish health suggests that phages can be used as disease treatment. Such advances represent milestones in our understanding of gut phages in human health and should fuel research on their role in health and disease. PMID:28594392

  12. Methodological and technological implications of quantitative human movement analysis in long term space flights.

    Science.gov (United States)

    Ferrigno, G; Baroni, G; Pedotti, A

    1999-04-01

    In the frame of the 179-days EUROMIR '95 space mission, two in-flight experiments foresaw the analysis of three-dimensional human movements in microgravity. For this aim, a space qualified opto-electronic motion analyser based on passive markers was installed onboard the MIR Space Station. The paper describes the experimental procedures designed in order to face technical and operational limitations imposed by the critical environment of the orbital module. The reliability of the performed analysis is discussed, focusing two related aspects: accuracy in three-dimensional marker localisation and data comparability among different experimental sessions. The effect of the critical experimental set-up and of TV cameras optical distortions is evaluated on in-flight acquired data, by performing an analysis on Euclidean distance conservation on rigid bodies. An optimisation method for the recovering of a unique reference frame throughout the whole mission is described. Results highlight the potentiality that opto-electronics and close-range photogrammetry have for automatic motion analysis onboard orbital modules. The discussion of the obtained results provides general suggestions for the implementation of experimental human movement analysis in critical environments, based on the suitable trade-off between external constraints and achievable analysis reliability.

  13. Effect of quinolinic acid on human astrocytes morphology and functions: implications in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Brew Bruce J

    2009-12-01

    Full Text Available Abstract The excitotoxin quinolinic acid (QUIN is synthesized through the kynurenine pathway (KP by activated monocyte lineage cells. QUIN is likely to play a role in the pathogenesis of several major neuroinflammatory diseases including Alzheimer's disease (AD. The presence of reactive astrocytes, astrogliosis, increased oxidative stress and inflammatory cytokines are important pathological hallmarks of AD. We assessed the stimulatory effects of QUIN at low physiological to high excitotoxic concentrations in comparison with the cytokines commonly associated with AD including IFN-γ and TNF-α on primary human astrocytes. We found that QUIN induces IL-1β expression, a key mediator in AD pathogenesis, in human astrocytes. We also explored the effect of QUIN on astrocyte morphology and functions. At low concentrations, QUIN treatment induced concomitantly a marked increase in glial fibrillary acid protein levels and reduction in vimentin levels compared to controls; features consistent with astrogliosis. At pathophysiological concentrations QUIN induced a switch between structural protein expressions in a dose dependent manner, increasing VIM and concomitantly decreasing GFAP expression. Glutamine synthetase (GS activity was used as a functional metabolic test for astrocytes. We found a significant dose-dependent reduction in GS activity following QUIN treatment. All together, this study showed that QUIN is an important factor for astroglial activation, dysregulation and cell death with potential relevance to AD and other neuroinflammatory diseases.

  14. Metabolic Biosynthesis of Potato (Solanum tuberosum l.) Antioxidants and Implications for Human Health.

    Science.gov (United States)

    Lovat, Christie; Nassar, Atef M K; Kubow, Stan; Li, Xiu-Qing; Donnelly, Danielle J

    2016-10-25

    Potato (Solanum tuberosum L.) is common, affordable, readily stored, easily prepared for consumption, and nutritious. For these reasons, potato has become one of the top five crops consumed worldwide. Consequently, it is important to understand its contribution to both our daily and long-term health. Potato is one of the most important sources of antioxidants in the human diet. As such, it supports the antioxidant defense network in our bodies that reduces cellular and tissue toxicities that result from free radical-induced protein, lipid, carbohydrate, and DNA damage. In this way, potato antioxidants may reduce the risk for cancers, cardiovascular diseases, diabetes, and even radiation damage. A better understanding of these components of potato is needed by the food industry, health professionals, and consumers. This review provides referenced summaries of all of the antioxidant groups present in potato tubers and updated schematics including genetic regulation for the major antioxidant biosynthesis pathways. This review complements current knowledge on the role of potato in human health. We hope it will provide impetus toward breeding efforts to develop cultivars with increased antioxidant capacity as 'functional foods' and encourage potato consumers and processors to work toward preservation of antioxidant capacity in cooked potato and potato products.

  15. Arsenic translocation in rice cultivation and its implication for human health

    Directory of Open Access Journals (Sweden)

    José M Bastías

    2016-03-01

    Full Text Available Arsenic (As is a toxic metalloid for plants and animals. Large amounts of As have been released in arable soils through anthropogenic activities, use of contaminated irrigation water, and mining among others. Rice (Oryza sativa L. is one of the most consumed cereals worldwide; it is an important route of exposure for As. The objective of this review was to explain possible mechanisms involved in As absorption that contaminate rice plant through the soil and water, and to mention studies that have been conducted to minimize the risk of human exposure. The root is able to absorb and accumulate large amounts of As, but only small amounts are translocated to the grain and tillers. Arsenic concentrations in rice tissues decrease from the root to the grain. Information about As translocation in rice is sparse and research is directed toward studying the molecular mechanism of absorption and accumulation in the grain because it has not yet been explained. Some rice varieties have been developed that are resistant to high soil As concentrations and are not able to translocate the metalloid toward the root. Many studies suggest that not all ingested inorganic As accumulated in the gastrointestinal tract is absorbed into the bloodstream and produces toxicity. It is therefore recommended that As bioavailability be evaluated in imported or domestic Chilean rice to more precisely estimate human health risk

  16. Human metabolism of lapatinib, a dual kinase inhibitor: implications for hepatotoxicity.

    Science.gov (United States)

    Castellino, Stephen; O'Mara, Michael; Koch, Kevin; Borts, David J; Bowers, Gary D; MacLauchlin, Christopher

    2012-01-01

    Lapatinib (Tykerb, Tyverb) is an important orally active dual tyrosine kinase inhibitor efficacious in combination therapy for patients with progressive human epidermal receptor 2-overexpressing metastatic breast cancer. However, clinically significant liver injury, which may be associated with lapatinib metabolic activation, has been reported. We describe the metabolism and excretion of [(14)C]lapatinib in six healthy human volunteers after a single oral dose of 250 mg and the potential relationships between metabolism and clinical hepatotoxicity. Overall, elimination showed high intersubject variability, with fecal elimination being the predominant pathway, representing a median of 92% of the dose with lapatinib as the largest component (approximate median 27% of the dose). In plasma, approximately 50% of the observed radioactivity was attributed to metabolites. Analysis of a 4-h pooled plasma extract identified seven metabolites related by an N- and α-carbon oxidation cascade. Fecal metabolites derived from three prominent pathways: N- and α-carbon oxidation, fluorobenzyl oxidative cleavage, and hydroxypyridine formation. Several of the lapatinib metabolites can undoubtedly be linked to reactive species such as aldehydes or quinone imines. In addition to the contribution of these potentially reactive metabolites as suspects in clinical liver injury, the role of other disposition factors, including interaction with drug transporters, pharmacogenetics, or magnitude of the therapeutic dose, should not be discounted.

  17. Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene

    Science.gov (United States)

    Bassuk, Alexander G.; Muthuswamy, Lakshmi B.; Boland, Riley; Smith, Tiffany L.; Hulstrand, Alissa M.; Northrup, Hope; Hakeman, Matthew; Dierdorff, Jason M.; Yung, Christina K.; Long, Abby; Brouillette, Rachel B.; Au, Kit Sing; Gurnett, Christina; Houston, Douglas W.; Cornell, Robert A.; Manak, J. Robert

    2013-01-01

    Neural tube defects (NTDs) are common birth defects of complex etiology. Family and population-based studies have confirmed a genetic component to NTDs. However, despite more than three decades of research, the genes involved in human NTDs remain largely unknown. We tested the hypothesis that rare copy number variants (CNVs), especially de novo germline CNVs, are a significant risk factor for NTDs. We used array-based comparative genomic hybridization (aCGH) to identify rare CNVs in 128 Caucasian and 61 Hispanic patients with non-syndromic lumbar-sacral myelomeningocele. We also performed aCGH analysis on the parents of affected individuals with rare CNVs where parental DNA was available (42 sets). Among the eight de novo CNVs that we identified, three generated copy number changes of entire genes. One large heterozygous deletion removed 27 genes, including PAX3, a known spina bifida-associated gene. A second CNV altered genes (PGPD8, ZC3H6) for which little is known regarding function or expression. A third heterozygous deletion removed GPC5 and part of GPC6, genes encoding glypicans. Glypicans are proteoglycans that modulate the activity of morphogens such as Sonic Hedgehog (SHH) and bone morphogenetic proteins (BMPs), both of which have been implicated in NTDs. Additionally, glypicans function in the planar cell polarity (PCP) pathway, and several PCP genes have been associated with NTDs. Here, we show that GPC5 orthologs are expressed in the neural tube, and that inhibiting their expression in frog and fish embryos results in NTDs. These results implicate GPC5 as a gene required for normal neural tube development. PMID:23223018

  18. Site-directed Mutagenesis Reveals Regions Implicated in the Stability and Fiber Formation of Human λ3r Light Chains*

    Science.gov (United States)

    Villalba, Miryam I.; Canul-Tec, Juan C.; Luna-Martínez, Oscar D.; Sánchez-Alcalá, Rosalba; Olamendi-Portugal, Timoteo; Rudiño-Piñera, Enrique; Rojas, Sonia; Sánchez-López, Rosana; Fernández-Velasco, Daniel A.; Becerril, Baltazar

    2015-01-01

    Light chain amyloidosis (AL) is a disease that affects vital organs by the fibrillar aggregation of monoclonal light chains. λ3r germ line is significantly implicated in this disease. In this work, we contrasted the thermodynamic stability and aggregation propensity of 3mJL2 (nonamyloidogenic) and 3rJL2 (amyloidogenic) λ3 germ lines. Because of an inherent limitation (extremely low expression), Cys at position 34 of the 3r germ line was replaced by Tyr reaching a good expression yield. A second substitution (W91A) was introduced in 3r to obtain a better template to incorporate additional mutations. Although the single mutant (C34Y) was not fibrillogenic, the second mutation located at CDR3 (W91A) induced fibrillogenesis. We propose, for the first time, that CDR3 (position 91) affects the stability and fiber formation of human λ3r light chains. Using the double mutant (3rJL2/YA) as template, other variants were constructed to evaluate the importance of those substitutions into the stability and aggregation propensity of λ3 light chains. A change in position 7 (P7D) boosted 3rJL2/YA fibrillogenic properties. Modification of position 48 (I48M) partially reverted 3rJL2/YA fibril aggregation. Finally, changes at positions 8 (P8S) or 40 (P40S) completely reverted fibril formation. These results confirm the influential roles of N-terminal region (positions 7 and 8) and the loop 40–60 (positions 40 and 48) on AL. X-ray crystallography revealed that the three-dimensional topology of the single and double λ3r mutants was not significantly altered. This mutagenic approach helped to identify key regions implicated in λ3 AL. PMID:25505244

  19. Cerebellar Purkinje cells incorporate immunoglobulins and immunotoxins in vitro: implications for human neurological disease and immunotherapeutics

    Directory of Open Access Journals (Sweden)

    Rose John W

    2009-10-01

    Full Text Available Abstract Background Immunoglobulin G (IgG antibodies reactive with intracellular neuronal proteins have been described in paraneoplastic and other autoimmune disorders. Because neurons have been thought impermeable to immunoglobulins, however, such antibodies have been considered unable to enter neurons and bind to their specific antigens during life. Cerebellar Purkinje cells - an important target in paraneoplastic and other autoimmune diseases - have been shown in experimental animals to incorporate a number of molecules from cerebrospinal fluid. IgG has also been detected in Purkinje cells studied post mortem. Despite the possible significance of these findings for human disease, immunoglobulin uptake by Purkinje cells has not been demonstrated in living tissue or studied systematically. Methods To assess Purkinje cell uptake of immunoglobulins, organotypic cultures of rat cerebellum incubated with rat IgGs, human IgG, fluorescein-conjugated IgG, and rat IgM were studied by confocal microscopy in real time and following fixation. An IgG-daunorubicin immunotoxin was used to determine whether conjugation of pharmacological agents to IgG could be used to achieve Purkinje cell-specific drug delivery. Results IgG uptake was detected in Purkinje cell processes after 4 hours of incubation and in Purkinje cell cytoplasm and nuclei by 24-48 hours. Uptake could be followed in real time using IgG-fluorochrome conjugates. Purkinje cells also incorporated IgM. Intracellular immunoglobulin did not affect Purkinje cell viability, and Purkinje cells cleared intracellular IgG or IgM within 24-48 hours after transfer to media lacking immunoglobulins. The IgG-daunomycin immunotoxin was also rapidly incorporated into Purkinje cells and caused extensive, cell-specific death within 8 hours. Purkinje cell death was not produced by unconjugated daunorubicin or control IgG. Conclusion Purkinje cells in rat organotypic cultures incorporate and clear host (rat and non

  20. Human factors perspective on the prescribing behavior of recent medical graduates: implications for educators

    Directory of Open Access Journals (Sweden)

    Gordon M

    2013-01-01

    Full Text Available Morris Gordon,1,2 Ken Catchpole,3 Paul Baker1,41Faculty of Health and Social Care, University of Salford, Salford, UK; 2Department of Paediatrics, Fairfield General Hospital, Bury, UK; 3Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 4North Western Deanery, Manchester, UKBackground: Junior doctors are at high risk of involvement in medication errors. Educational interventions to enhance human factors and specifically nontechnical skills in health care are increasingly reported, but there is no work in the context of prescribing improvement to guide such education. We set out to determine the elements that influence prescribing from a human factors perspective by recent medical graduates and use this to guide education in this area.Methods: A total of 206 recent medical graduates of the North Western Foundation School were asked to describe their views on safety practices and behaviors. Free text data regarding prescribing behaviors were collected 1, 2, and 4 months after starting their posts. A 94.1% response rate was achieved. Qualitative analysis of data was completed using the constant comparison method. Five initial categories were developed, and the researchers subsequently developed thematic indices according to their understanding of the emerging content of the data. Further data were collected through group interviews 8–9 months into the placement to ensure thematic saturation.Results: Six themes were established at the axial coding level, ie, contributors to inappropriate prescribing, contributors to appropriate prescribing, professional responsibility, prescribing error, current practices, and methods for improvement of prescribing. Utilizing appropriate theoretical elements, we describe how recent medical graduates employ situational and error awareness to guide risk assessment.Conclusion: We have modeled the human factors of prescribing behavior by recent medical graduates. As these factors are related to

  1. Compositional dynamics of the human intestinal microbiota with aging: implications for health.

    Science.gov (United States)

    Lakshminarayanan, B; Stanton, C; O'Toole, P W; Ross, R P

    2014-11-01

    The human gut contains trillions of microbes which form an essential part of the complex ecosystem of the host. This microbiota is relatively stable throughout adult life, but may fluctuate over time with aging and disease. The gut microbiota serves a number of functions including roles in energy provision, nutrition and also in the maintenance of host health such as protection against pathogens. This review summarizes the age-related changes in the microbiota of the gastrointestinal tract (GIT) and the link between the gut microbiota in health and disease. Understanding the composition and function of the gut microbiota along with the changes it undergoes overtime should aid the design of novel therapeutic strategies to counteract such alterations. These strategies include probiotic and prebiotic preparations as well as targeted nutrients, designed to enrich the gut microbiota of the aging population.

  2. Zone-dependent changes in human vertebral trabecular bone: clinical implications

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Ebbesen, Ebbe Nils; Mosekilde, Lis

    2002-01-01

    We have previously shown that there are pronounced age-related changes in human vertebral cancellous bone density and microarchitecture. However, the magnitude of these changes seemed to be dependent on zone location in the vertebral body-the central third vs. the areas adjacent to the endplates....... The aim of the present study was, therefore, to investigate whether such zone-specific differences could be identified by static histomorphometric measures. The material comprised 48 individuals (24 women aged 19-97 years, and 24 men aged 23-95 years). Three of the women had a known fracture of the L-2....... From each L-2, thick frontal sections of half of the vertebra were embedded undecalcified in methylmethacrylate, cut into 10-microm-thick sections, and stained with aniline blue. The sections were scanned into a computer, and classic static histomorphometry was performed on the images...

  3. Ages for the Middle Stone Age of southern Africa: implications for human behavior and dispersal.

    Science.gov (United States)

    Jacobs, Zenobia; Roberts, Richard G; Galbraith, Rex F; Deacon, Hilary J; Grün, Rainer; Mackay, Alex; Mitchell, Peter; Vogelsang, Ralf; Wadley, Lyn

    2008-10-31

    The expansion of modern human populations in Africa 80,000 to 60,000 years ago and their initial exodus out of Africa have been tentatively linked to two phases of technological and behavioral innovation within the Middle Stone Age of southern Africa-the Still Bay and Howieson's Poort industries-that are associated with early evidence for symbols and personal ornaments. Establishing the correct sequence of events, however, has been hampered by inadequate chronologies. We report ages for nine sites from varied climatic and ecological zones across southern Africa that show that both industries were short-lived (5000 years or less), separated by about 7000 years, and coeval with genetic estimates of population expansion and exit times. Comparison with climatic records shows that these bursts of innovative behavior cannot be explained by environmental factors alone.

  4. Human placental extract mediated inhibition of proteinase K: implications of heparin and glycoproteins in wound physiology.

    Science.gov (United States)

    Sharma, Kanika; Mukherjee, Chaitali; Roy, Siddhartha; De, Debashree; Bhattacharyya, Debasish

    2014-09-01

    Efficient debridement of the wound bed following the removal of microbial load prevents its progression into a chronic wound. Bacterial infection and excessive proteolysis characterize impaired healing and therefore, their inhibition might restore the disturbed equilibrium in the healing process. Human placental extract exhibits reversible, non-competitive inhibition towards Proteinase K, a microbial protease, by stabilizing it against auto-digestion. Scattering and fluorescence studies followed by biochemical analysis indicated the involvement of a glycan moiety. Surface plasmon resonance demonstrated specific interaction of heparin with Proteinase K having Kd in μM range. Further, Proteinase K contains sequence motifs similar to other heparin-binding proteins. Molecular docking revealed presence of clefts suitable for binding of heparin-derived oligosaccharides. Comprehensive analysis of this inhibitory property of placental extract partly explains its efficacy in curing wounds with common bacterial infections.

  5. Salmonellae in food stuffs of plant origin and their implications on human health.

    Science.gov (United States)

    Krtinić, G; Durić, P; Ilić, S

    2010-11-01

    Salmonella enterica is one of the most common causes of food-borne infection in human beings. Cases of Salmonella infection have been decreasing in Europe in the last ten years, yet, Salmonella infections are still the main cause of acute diarrhea syndrome. Globalization has caused the international food industry to increase the production of collective nutrition produce and products. This has intensified the need for authorized and accredited laboratories to monitor microbiological food safety. All parameters indicate the necessity of a multi-sector approach to this problem. Food safety supervision involves the analysis and identification of risk management, as well as the monitoring, evaluating, and regulating of crop irrigation. We can be more certain with a multi-sector approach that the number of Salmonella infections caused by plant-originated food stuffs will not increase in the future.

  6. Human physiological adaptation to extended Space Flight and its implications for Space Station

    Science.gov (United States)

    Kutyna, F. A.; Shumate, W. H.

    1985-01-01

    Current work evaluating short-term space flight physiological data on the homeostatic changes due to weightlessness is presented as a means of anticipating Space Station long-term effects. An integrated systems analysis of current data shows a vestibulo-sensory adaptation within days; a loss of body mass, fluids, and electrolytes, stabilizing in a month; and a loss in red cell mass over a month. But bone demineralization which did not level off is seen as the biggest concern. Computer algorithms have been developed to simulate the human adaptation to weightlessness. So far these paradigms have been backed up by flight data and it is hoped that they will provide valuable information for future Space Station design. A series of explanatory schematics is attached.

  7. Comparative modelling of human β tubulin isotypes and implications for drug binding

    Science.gov (United States)

    Torin Huzil, J.; Ludueña, Richard F.; Tuszynski, Jack

    2006-02-01

    The protein tubulin is a target for several anti-mitotic drugs, which affect microtubule dynamics, ultimately leading to cell cycle arrest and apoptosis. Many of these drugs, including the taxanes and Vinca alkaloids, are currently used clinically in the treatment of several types of cancer. Another tubulin binding drug, colchicine, although too toxic to be used as a chemotherapeutic agent, is commonly used for the treatment of gout. The main disadvantage that all of these drugs share is that they bind tubulin indiscriminately, leading to the death of both cancerous and healthy cells. However, the broad cellular distribution of several tubulin isotypes provides a platform upon which to construct novel chemotherapeutic drugs that could differentiate between different cell types, reducing the undesirable side effects associated with current chemotherapeutic treatments. Here, we report an analysis of ten human β tubulin isotypes and discuss differences within each of the previously characterized paclitaxel, colchicine and vinblastine binding sites.

  8. Implication of HLA-C and KIR alleles in human papillomavirus infection and associated cervical lesions.

    Science.gov (United States)

    Rizzo, Roberta; Gentili, Valentina; Rotola, Antonella; Bortolotti, Daria; Cassai, Enzo; Di Luca, Dario

    2014-11-01

    Human papillomavirus (HPV) regulation of host immune response leads to cervical lesions. In particular, natural killer (NK) cells are crucial for HPV control. Since specific HLA-I/KIR interactions modify NK cell activation, we analyzed HLA-C and KIR alleles in HPV infection and lesion development in 150 controls, 33 condyloma acuminatum, and 111 invasive cervical cancer (ICC) patients. We showed an increase in HLA-C1/KIR2DL2 and HLA-C1/KIR2DL3 pairs in HPV high-risk infected patients (OR 3.05, 3.24) with ICC (OR 1.33, 3.68). These data suggest HLA-C and KIR typing as risk marker for HPV infection and lesion evolution.

  9. Seagrass meadows globally as a coupled social-ecological system: implications for human wellbeing.

    Science.gov (United States)

    Cullen-Unsworth, Leanne C; Nordlund, Lina Mtwana; Paddock, Jessica; Baker, Susan; McKenzie, Len J; Unsworth, Richard K F

    2014-06-30

    Seagrass ecosystems are diminishing worldwide and repeated studies confirm a lack of appreciation for the value of these systems. In order to highlight their value we provide the first discussion of seagrass meadows as a coupled social-ecological system on a global scale. We consider the impact of a declining resource on people, including those for whom seagrass meadows are utilised for income generation and a source of food security through fisheries support. Case studies from across the globe are used to demonstrate the intricate relationship between seagrass meadows and people that highlight the multi-functional role of seagrasses in human wellbeing. While each case underscores unique issues, these examples simultaneously reveal social-ecological coupling that transcends cultural and geographical boundaries. We conclude that understanding seagrass meadows as a coupled social-ecological system is crucial in carving pathways for social and ecological resilience in light of current patterns of local to global environmental change.

  10. ECONOMIC IMPLICATIONS OF CHURCHES IN THE DEVELOPMENT OF HUMAN SETTLEMETS. STUDY CASE: IASI CITY

    Directory of Open Access Journals (Sweden)

    Alexandra Georgiana PARASCA

    2014-12-01

    Full Text Available It is not wrong said that monasteries and churches were one of the elements that led to the development of human settlements in Iasi, especially the city of Iasi. Most churches/monasteries from the feudal period, received from princes / noblemen vast areas of land in order to develop economically, so buildings can survive in time, but also the administrators. Gradually, this lands got to be populated by those who worked and eventually they built houses to live closer to the land they worked on. Subsequently, these small settlements led to the formation of rural settlements and with time they gained an urban character. Today, we have reached the stage where these religious buildings have grown importance in the development of tourism, attracting tourists from around the country and abroad.

  11. Expression of Adiponectin Receptors in Human Placenta and Its Possible Implication in Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Naglaa F. Al Husseini

    2010-01-01

    Full Text Available Problem statement: Similar to obese patients and type 2 diabetic patients, adiponectin levels are reduced in former Gestational Diabetes Mellitus (GDM patients and are lower in GDM women during late pregnancy compared with pregnant control subjects matched for BMI. Diabetic insult at later stages in gestation, such as may occur in gestational diabetes, will foremost lead to short-term changes in a variety of molecules for key functions including gene expression in the placenta. Approach: In this study we assessed the expression of adiponectin receptors in human placenta to identify the site (s of expression and to clarify the effect of gestational diabetes in this expression. This study was carried on 10 normoglycemic pregnant women and 20 GDM women. The placental tissue was collected immediately after delivery and tissue biopsies were taken from both fetal and maternal sides of each placenta. One step-RT-PCR for ADIPOR1 and ADIPOR2 was done by Real Time PCR using Syber Green technique. Relative quantification of mRNA of the ADIPOR1 and ADIPOR2 genes was measured using ABI7900 Real Time machine. Results: Both types of Adiponectin Receptors (ADIPOR1 and ADIPOR2 are expressed in human placenta. ADIPOR1 is more highly expressed than ADIPOR2 in both fetal and maternal sides of GDM cases and normal pregnant women. ADIPOR1 mRNA expression was significantly up regulated in GDM women compared to normal pregnant women, whereas no significant difference in the expression of ADIPOR2 was detected between the two groups. There was no evidence of maternal-fetal side difference in the expression of adiponectin receptors in GDM cases but in normal pregnant women there is a statistically significant difference between both sides in the expression of both ADIPOR1 and ADIPOR2. Conclusion: We concluded that adiponectin plays an important role in mediation the glucose metabolism in fetal tissues through its receptors, mainly Adiponectin Receptor 1 (ADIPOR1.

  12. Collagen in Human Tissues: Structure, Function, and Biomedical Implications from a Tissue Engineering Perspective

    Science.gov (United States)

    Balasubramanian, Preethi; Prabhakaran, Molamma P.; Sireesha, Merum; Ramakrishna, Seeram

    The extracellular matrix is a complex biological structure encoded with various proteins, among which the collagen family is the most significant and abundant of all, contributing 30-35% of the whole-body protein. "Collagen" is a generic term for proteins that forms a triple-helical structure with three polypeptide chains, and around 29 types of collagen have been identified up to now. Although most of the members of the collagen family form such supramolecular structures, extensive diversity exists between each type of collagen. The diversity is not only based on the molecular assembly and supramolecular structures of collagen types but is also observed within its tissue distribution, function, and pathology. Collagens possess complex hierarchical structures and are present in various forms such as collagen fibrils (1.5-3.5 nm wide), collagen fibers (50-70 nm wide), and collagen bundles (150-250 nm wide), with distinct properties characteristic of each tissue providing elasticity to skin, softness of the cartilage, stiffness of the bone and tendon, transparency of the cornea, opaqueness of the sclera, etc. There exists an exclusive relation between the structural features of collagen in human tissues (such as the collagen composition, collagen fibril length and diameter, collagen distribution, and collagen fiber orientation) and its tissue-specific mechanical properties. In bone, a transverse collagen fiber orientation prevails in regions of higher compressive stress whereas longitudinally oriented collagen fibers correlate to higher tensile stress. The immense versatility of collagen compels a thorough understanding of the collagen types and this review discusses the major types of collagen found in different human tissues, highlighting their tissue-specific uniqueness based on their structure and mechanical function. The changes in collagen during a specific tissue damage or injury are discussed further, focusing on the many tissue engineering applications for

  13. Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases

    Directory of Open Access Journals (Sweden)

    Adil Aldhahrani

    2017-03-01

    Full Text Available Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B. The immortalised human bronchial epithelial cell line (BEAS-2B was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

  14. Radiotherapy infrastructure and human resources in Europe - present status and its implications for 2020.

    Science.gov (United States)

    Datta, Niloy Ranjan; Samiei, Massoud; Bodis, Stephan

    2014-10-01

    Radiotherapy (RT) is required for nearly half of the newly diagnosed cancer patients. To optimise the quality and availability of RT, guidelines have been proposed by European Society for Radiotherapy and Oncology-QUAntification of Radiation Therapy Infrastructure And Staffing Needs (ESTRO-QUARTS) and the International Atomic Energy Agency (IAEA). This study evaluates the present status of RT capacity in Europe and the projected needs by 2020 as per these recommendations. Thirty-nine of the 53 countries, listed in Europe by the UN Statistical Division, whose cancer incidences, teletherapy and human resources were available in the Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN), International Agency for Research on Cancer (IARC) and DIrectory of RAdiotherapy Centres (DIRAC) (IAEA) databases were evaluated. A total of 3550 teletherapy units (TRT), 7017 radiation oncologists (RO), 3685 medical physicists (MP) and 12,788 radiotherapy technologists (RTT) are presently available for the 3.44 million new cancer cases reported annually in these countries. The present infrastructure and human resources in RT are estimated to provide RT access to 74.3% of the patients requiring RT. The current capacity in TRT, RO, MP and RTT when compared with recommended guidelines has a deficit of 25.6%, 18.3%, 22.7% and 10.6%, respectively. Thus, to respond to requirements by 2020, the existing capacity needs to be augmented by an additional 1698 TRTs, 2429 ROs, 1563 MPs and 2956 RTTs. With an imminent rise in cancer incidence, multifaceted strategic planning at national and international levels within a coordinated comprehensive cancer control programme is highly desirable to give adequate access to all patients who require radiotherapy across Europe. Specific steps to address this issue at national and continental levels involving all major stakeholders are proposed.

  15. Urinary concentrations of parabens in Chinese young adults: implications for human exposure.

    Science.gov (United States)

    Ma, Wan-Li; Wang, Lei; Guo, Ying; Liu, Li-Yan; Qi, Hong; Zhu, Ning-Zheng; Gao, Chong-Jing; Li, Yi-Fan; Kannan, Kurunthachalam

    2013-10-01

    Parabens are widely used as preservatives in foods, cosmetics, and pharmaceuticals. However, recent studies have indicated that high and systemic exposure to parabens can be harmful to human health. Although a few studies have reported urinary paraben levels in western countries, studies on paraben exposure in the Chinese population are limited. China is currently a major producer of parabens in the world. In this study, 109 urine samples collected from Chinese young adults (approximately 20 years old) were analyzed for five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens) by high-performance liquid chromatography-tandem mass spectrometry. Methyl-, propyl-, and ethyl-parabens were the three major paraben analogues found in all (100%) samples. The concentration of the sum of the five parabens ranged from 0.82 to 728 ng/mL with a geometric mean value of 17.4 ng/mL. Urinary concentration of parabens was 2-fold greater in females than in males. Based on the measured urinary concentrations, daily intake of parabens by the Chinese young adults was estimated and compared with those reported for United States adults. The estimated daily intakes (EDIurine) of parabens were 18.4 and 40.8 μg/kg bw/day for Chinese males and females, respectively, values that were lower than those reported for United States adults (74.7 μg/kg bw/day). Based on the reported concentrations of parabens in foods from China and the United States, the contribution of dietary intake to EDIurine was estimated to be 5.5, 2.6, and 0.42% for Chinese males, Chinese females, and United States adults, respectively, which indicates the significance of nondietary sources of parabens to human exposures.

  16. The primate vaginal microbiome: comparative context and implications for human health and disease.

    Science.gov (United States)

    Stumpf, Rebecca M; Wilson, Brenda A; Rivera, Angel; Yildirim, Suleyman; Yeoman, Carl J; Polk, John D; White, Bryan A; Leigh, Steven R

    2013-12-01

    The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host-microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive-age humans show distinct microbial communities, generally dominated by Lactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host-microbe coevolution and adaptation.

  17. Human-use antibacterial residues in the natural environment of China: implication for ecopharmacovigilance.

    Science.gov (United States)

    Wang, Jun; He, Bingshu; Hu, Xiamin

    2015-06-01

    Antibacterial residues in the natural environment have been of increasing concern due to their impact on bacteria resistance development and toxicity to natural communities and ultimately to public health. China is a large country with high production and consumption of antibacterials for its population growth and economic development in recent years. In this article, we summarized the current situation of human-use antibacterial pollution in Chinese water (wastewaters, natural and drinking waters) and solid matrices (sludge, sediment, and soil) reported in 33 peer-reviewed papers. We found that, although there are adequate wastewater treatment systems in China, human-use antibacterial residues in the natural environment were reported almost throughout the whole country. Three most frequently prescribed classes of antibacterials in China, including quinolones, macrolides, and β-lactam, were also the predominant classes of residues in Chinese environment, manifested as the high concentration and detection frequency. In view of this alarming situation, we have presented that ecopharmacovigilance (EPV) might be implemented in the antibacterial drug administration of China, as the active participation of the pharmaceutical industry and drug regulatory authorities from the diffuse source of antibacterial pollution. Considering EPV experience of developed countries together with the actual conditions of China, we have identified some approaches that can be taken, including:• Focus on education;• Further strengthening and persevering the antibacterial stewardship strategies and pharmaceutical take-back programs in China;• Designing greener antibacterials with better degradability in the environment;• Implementing environmental risk assessment prior to launch of new drugs;• Strengthening collaboration in EPV-related areas.

  18. The vascular anatomy of the human temporalis muscle: implications for surgical splitting techniques.

    Science.gov (United States)

    Cheung, L K

    1996-12-01

    Despite the wide application of the temporalis muscle flap and its modifications, understanding of the vascular pattern and territories within the muscle remains poor. This study aimed to evaluate the vascular architecture in the human temporalis muscle for surgical application. The material comprised 15 fresh cadavers (30 muscle specimens), which were divided into three groups for vascular infusion by either Indian ink solution, lead oxide solution, or methylmethacrylate resin. The vascular network in the temporalis muscle was analyzed by stereomicroscopy, radiography, and scanning electron microscopy. The human temporalis muscle was found to have vascular supply from three primary arteries: the anterior deep temporal artery (ADTA), the posterior deep temporal artery (PDTA), and the middle temporal artery (MTA). Each primary artery branched into the secondary arterioles and then the terminal arterioles. The venous network accompanied the arteries, and double veins pairing one artery was a common finding. The capillaries formed a dense, interlacing network with orientation along the muscle fibres. Arteriovenous anastomosis was absent. In the coronal plane, the vessels were located mainly on the lateral and medial aspects of the muscle with a significantly lower vascular density in the midline. Morphometric analysis of the arterial network showed that the PDTA was larger in size at primary and secondary branching levels than the ADTA and the MTA, whereas no differences were present at the terminal arteriolar levels. The distribution of the arterial territories was as follows: the ADTA occupied 21% anteriorly, the PDTA occupied 41% in the middle region, and the MTA occupied 38% in the posterior region. This improved understanding of the vascular architecture within the temporalis muscle complements the anatomic basis of the flap-splitting technique and increases the safety of its application.

  19. Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine.

    Science.gov (United States)

    May, A; Shepheard, S L; Knorr, M; Effert, R; Wessing, A; Hargreaves, R J; Goadsby, P J; Diener, H C

    1998-07-01

    High-intensity electrical stimulation of the trigeminal ganglion is accompanied by mast cell degranulation, vasodilatation, increased endothelial permeability and leakage of albumin from postcapillary venules within the dura mater. Overall, the histological appearance suggests an evolving sterile inflammatory response. This neurogenic inflammation within the meninges has been suggested as a model to explain the pain in migraine and cluster headache, and has been used to characterize the pharmacology of anti-migraine compounds. Using the rat model of neurogenic inflammation, the albumin extravasation ratio (stimulated : unstimulated side) in vehicle-treated animals in the dura and retina was 1.60 +/- 0.11 and 1.76 +/- 0.18, respectively (n = 10; values are mean +/- SEM). Pretreatment with sumatriptan (n = 9) produced a highly significant reduction in the ratio of extravasation within the dura to 1.10 +/- 0.06 (P = 0.002) and in the retina to 0.96 +/- 0.06 (P = 0.001), as did the neurokinin-1 receptor antagonist RP 67580 (n = 12) in the dura (1.04 +/- 0.11, P = 0.002) and retina (1.08 +/- 0.06, P = 0.001). These data demonstrate increased endothelial permeability and leakage of albumin not only in the dura but also in the retina. In a second stage we investigated possible extravasation in the human retina in acute migraine (n = 8) and cluster headache (n = 5) using fluorescein or indocyanine angiography. No increased endothelial permeability or leakage of dye could be found in the human retinal or choroidal vessels during headache attacks or in the headache-free interval in persons suffering from both migraine and cluster headache. These data raise the possibility that neurogenic inflammation is not a major factor in headache attacks in migraine or cluster headache.

  20. Implications of Vertebrate Craniodental Evo-Devo for Human Oral Health.

    Science.gov (United States)

    Boughner, Julia C

    2017-06-01

    Highly processed diets eaten by postindustrial modern human populations coincide with higher frequencies of third molar impaction, malocclusion, and temporomandibular joint disorders that affect millions of people worldwide each year. Current treatments address symptoms, not causes, because the multifactorial etiologies of these three concerns mask which factors incline certain people to malocclusion, impaction, and/or joint issues. Deep scientific curiosity about the origins of jaws and dentitions continues to yield rich insights about the developmental genetic mechanisms that underpin healthy craniodental morphogenesis and integration. Mounting evidence from evolution and development (Evo-Devo) studies suggests that function is another mechanism important to healthy craniodental integration and fit. Starting as early as weaning, softer diets and thus lower bite forces appear to relax or disrupt integration of oral tissues, alter development and growth, and catalyze impaction, malocclusion, and jaw joint disorders. How developing oral tissues respond to bite forces remains poorly understood, but biomechanical feedback seems to alter balances of local bone resorption and deposition at the tooth-bone interface as well as affect tempos and amounts of facial outgrowth. Also, behavioral changes in jaw function and parafunction contribute to degeneration and pain in joint articular cartilages and masticatory muscles. The developmental genetic contribution to craniodental misfits and disorders is undeniable but still unclear; however, at present, human diet and jaw function remain important and much more actionable clinical targets. New Evo-Devo studies are needed to explain how function interfaces with craniodental phenotypic plasticity, variation, and evolvability to yield a spectrum of healthy and mismatched dentitions and jaws. © 2017 Wiley Periodicals, Inc.

  1. Occurrence and profiles of phthalates in foodstuffs from China and their implications for human exposure.

    Science.gov (United States)

    Guo, Ying; Zhang, Zifeng; Liu, Liyan; Li, Yifan; Ren, Nanqi; Kannan, Kurunthachalam

    2012-07-11

    Phthalate esters are used in a wide variety of consumer products, and human exposure to this class of compounds is widespread. Nevertheless, studies on dietary exposure of humans to phthalates are limited. In this study, nine phthalate esters were analyzed in eight categories of foodstuffs (n = 78) collected from Harbin and Shanghai, China, in 2011. Dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), benzyl butyl phthalate (BzBP), and diethylhexyl phthalate (DEHP) were frequently detected in food samples. DEHP was the major compound found in most of the food samples, with concentrations that ranged from below the limit of quantification (LOQ) to 762 ng/g wet weight (wt). The concentrations of phthalates in food samples from China were comparable to concentrations reported for several other countries, but the profiles were different; DMP was found more frequently in Chinese foods than in foods from other countries. The estimated daily dietary intake of phthalates (EDIdiet) was calculated based on the concentrations measured and the daily ingestion rates of food items. The EDIdiet values for DMP, DEP, DIBP, DBP, BzBP, and DEHP (based on mean concentrations) were 0.092, 0.051, 0.505, 0.703, 0.022, and 1.60 μg/kg-bw/d, respectively, for Chinese adults. The EDIdiet values calculated for phthalates were below the reference doses suggested by the United States Environmental Protection Agency (EPA). Comparison of total daily intakes, reported previously based on a biomonitoring study, with the current dietary intake estimates suggests that diet is the main source of DEHP exposure in China. Nevertheless, diet accounted for only phthalates.

  2. Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment.

    Directory of Open Access Journals (Sweden)

    David Gallego-Ortega

    Full Text Available BACKGROUND: The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKalpha and ChoKbeta isoforms, the first one with two different variants of splicing. Recently ChoKalpha has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKbeta in carcinogenesis has been reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we compare the in vitro and in vivo properties of ChoKalpha1 and ChoKbeta in lipid metabolism, and their potential role in carcinogenesis. Both ChoKalpha1 and ChoKbeta showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKbeta display an ethanolamine kinase role, ChoKalpha1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKalpha1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKbeta overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKalpha1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKbeta mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKalpha1 than ChoKbeta. CONCLUSION/SIGNIFICANCE: This study represents the first evidence of the distinct metabolic role of ChoKalpha and ChoKbeta isoforms, suggesting different physiological roles and implications in human

  3. Distinct biochemical properties of human serine hydroxymethyltransferase compared with the Plasmodium enzyme: implications for selective inhibition.

    Science.gov (United States)

    Pinthong, Chatchadaporn; Maenpuen, Somchart; Amornwatcharapong, Watcharee; Yuthavong, Yongyuth; Leartsakulpanich, Ubolsree; Chaiyen, Pimchai

    2014-06-01

    Serine hydroxymethyltransferase (SHMT) catalyzes the transfer of a hydroxymethyl group from l-serine to tetrahydrofolate to yield glycine and 5,10-methylenetetrahydrofolate. Our previous investigations have shown that SHMTs from Plasmodium spp. (P. falciparum, Pf; P. vivax, Pv) are different from the enzyme from rabbit liver in that Plasmodium SHMT can use d-serine as a substrate. In this report, the biochemical and biophysical properties of the Plasmodium and the human cytosolic form (hcSHMT) enzymes including ligand binding and kinetics were investigated. The data indicate that, similar to Plasmodium enzymes, hcSHMT can use d-serine as a substrate. However, hcSHMT displays many properties that are different from those of the Plasmodium enzymes. The molar absorption coefficient of hcSHMT-bound pyridoxal-5'-phosphate (PLP) is much greater than PvSHMT-bound or PfSHMT-bound PLP. The binding interactions of hcSHMT and Plasmodium SHMT with d-serine are different, as only the Plasmodium enzyme undergoes formation of a quinonoid-like species upon binding to d-serine. Furthermore, it has been noted that hcSHMT displays strong substrate inhibition by tetrahydrofolate (THF) (at THF > 40 μm), compared with SHMTs from Plasmodium and other species. The pH-activity profile of hcSHMT shows higher activities at lower pH values corresponding to a pKa value of 7.8 ± 0.1. Thiosemicarbazide reacts with hcSHMT following a one-step model [k1 of 12 ± 0.6 m(-1) ·s(-1) and k-1 of (1.0 ± 0.6) × 10(-3) s(-1) ], while the same reaction with PfSHMT involves at least three steps. All data indicated that the ligand binding environment of SHMT from human and Plasmodium are different, indicating that it should be possible to develop species-selective inhibitors in future studies. serine hydroxymethyltransferase, EC 2.1.2.1; 5,10-methylenetetrahydrofolate dehydrogenase, EC 1.5.1.5. © 2014 FEBS.

  4. Implication of Human Hair in Regaining Spilled Oil Further Creating A Production Rise in Oyster Mushrooms

    Science.gov (United States)

    Pandey, A.; Srivastava, P.; Singh, U.

    2016-12-01

    It is estimated that 4.9 million liters of petroleum are spilled into U.S. waters from vessels and pipelines in a typical year. Oil spill may be as huge as of 8 million barrels (The Persian Gulf oil spill of 1991). Oil-water separation processes using polymeric or inorganic membranes have been proposed as effective and cost competitive technologies but in present the commercial use of membrane in treatment of spilled oil is currently limited by their low efficiency as well as high capital and operating cost. Indian hair-market is a billion-dollar industry yearly exporting thousands of tones of thick and dark hairs. Hairs contain keratin, a family of fibrous structural proteins been proved to adsorb oils. Laboratory results conclude that one gram of human hair can selectively adsorb about 15.5301 grams of crude oil over water, following Frendlich's isotherm. We seek hair mats made up of hairs of size ≤5 inches, costing 37/ton from selected parts of Indian hair market. With a known adsorbing efficiency of 95% towards crude oil, an estimated desorption efficiency of 70% oil worth 0.8M per year can be regained in crude form from U.S. waters only. To ensure solid waste management of hairs, hair mats left with 30% of adsorbed oil can be utilized in the cultivation of oyster mushrooms, a 20-34/kg crop that grows best in 20-25°C ,80-90% relative humidity and oily conditions. This will reduce the growing period of crop ensuring yearly profit of $6.06M in U.S. only engaging variety of stakeholders over borders. Results thus obtained in this study present an economic, safer and sustainable technique to minimize oil loss due to oil spill in waters further ensuring a low labor-low cost technique of waste management that enhances the growth of an in-demand crop. Keywords: Oil Spill, Human Hair Mats, Adsorb, Oyster Mushrooms

  5. Public perceptions of snakes and snakebite management: implications for conservation and human health in southern Nepal.

    Science.gov (United States)

    Pandey, Deb Prasad; Subedi Pandey, Gita; Devkota, Kamal; Goode, Matt

    2016-06-02

    Venomous snakebite and its effects are a source of fear for people living in southern Nepal. As a result, people have developed a negative attitude towards snakes, which can lead to human-snake conflicts that result in killing of snakes. Attempting to kill snakes increases the risk of snakebite, and actual killing of snakes contributes to loss of biodiversity. Currently, snake populations in southern Nepal are thought to be declining, but more research is needed to evaluate the conservation status of snakes. Therefore, we assessed attitudes, knowledge, and awareness of snakes and snakebite by Chitwan National Park's (CNP) buffer zone (BZ) inhabitants in an effort to better understand challenges to snake conservation and snakebite management. The results of this study have the potential to promote biodiversity conservation and increase human health in southern Nepal and beyond. We carried out face-to-face interviews of 150 randomly selected CNP BZ inhabitants, adopting a cross-sectional mixed research design and structured and semi-structured questionnaires from January-February 2013. Results indicated that 43 % of respondents disliked snakes, 49 % would exterminate all venomous snakes, and 86 % feared snakes. Farmers were the most negative and teachers were the most ambivalent towards snakes. Respondents were generally unable to identify different snake species, and were almost completely unaware of the need of conserve snakes and how to prevent snakebites. Belief in a snake god, and the ability of snakes to absorb poisonous gases from the atmosphere were among many superstitions that appeared to predispose negativity towards snakes of BZ residents. People with predisposed negativity towards snakes were not proponents of snake conservation. Fear, negativity, ambivalence towards, and ignorance about, snakes and the need for snake conservation were strong indicators of the propensity to harm or kill snakes. It seems that if wanton killing of snakes continues

  6. The TCD[sub 50] and regrowth delay assay in human tumor xenografts: Differences and implications

    Energy Technology Data Exchange (ETDEWEB)

    Budach, W.; Budach, V.; Stuschke, M.; Dinges, S.; Sack, H. (Univ. of Essen (Germany))

    1993-01-15

    The response to irradiation of five human xenograft cell lines - a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma - were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120 mm[sup 3] under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD[sub 50]) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD[sub 50] was used in order to compare the data to previously published data from spheroids. The lowest TCD[sub 50] was found in the lymphoma with 24.9 Gy, whereas the TCD[sub 50] of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD[sub 50] was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD[sub 50] values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD[sub 50] and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size.

  7. SEASONAL MORTALITY PATTERNS IN NON-HUMAN PRIMATES: IMPLICATIONS FOR VARIATION IN SELECTION PRESSURES ACROSS ENVIRONMENTS

    Science.gov (United States)

    Gogarten, Jan F.; Brown, Leone M.; Chapman, Colin A.; Cords, Marina; Doran-Sheehy, Diane; Fedigan, Linda M.; Grine, Frederick E.; Perry, Susan; Pusey, Anne E.; Sterck, Elisabeth H. M.; Wich, Serge A.; Wright, Patricia C.

    2014-01-01

    Examining seasonal mortality patterns can yield insights into the drivers of mortality and thus potential selection pressures acting on individuals in different environments. We compiled adult and juvenile mortality data from nine wild non-human primate taxa to investigate the role of seasonality in patterns of mortality and address the following questions: Is mortality highly seasonal across species? Does greater environmental seasonality lead to more seasonal mortality patterns? If mortality is seasonal, is it higher during wet seasons or during periods of food scarcity? and Do folivores show less seasonal mortality than frugivores? We found seasonal mortality patterns in five of nine taxa, and mortality was more often tied to wet seasons than food-scarce periods, a relationship that may be driven by disease. Controlling for phylogeny, we found a positive relationship between the degree of environmental seasonality and mortality, with folivores exhibiting more seasonal mortality than frugivores. These results suggest that mortality patterns are influenced both by diet and degree of environmental seasonality. Applied to a wider array of taxa, analyses of seasonal mortality patterns may aid understanding of life-history evolution and selection pressures acting across a broad spectrum of environments and spatial and temporal scales. PMID:23025613

  8. International service trade and its implications for human resources for health: a case study of Thailand.

    Science.gov (United States)

    Wibulpolprasert, Suwit; Pachanee, Cha-Aim; Pitayarangsarit, Siriwan; Hempisut, Pintusorn

    2004-06-29

    This study aims at analysing the impact of international service trade on the health care system, particularly in terms of human resources for health (HRH), using Thailand as a case study. Information was gathered through a literature review and interviews of relevant experts, as well as a brainstorming session.It was found that international service trade has greatly affected the Thai health care system and its HRH. From 1965 to 1975 there was massive emigration of physicians from Thailand in response to increasing demand in the United States of America. The country lost about 1,500 physicians, 20% of its total number, during that period.External migration of health professionals occurred without relation to agreements on trade in services. It was also found that free trade in service sectors other than health could seriously affect the health care system and HRH. Free trade in financial services with free flow of low-interest foreign loans, which started in 1993 in Thailand, resulted in the mushrooming of urban private hospitals between 1994 and 1997. This was followed by intensive internal migration of health professionals from rural public to urban private hospitals.After the economic crisis in 1997, with the resulting downturn of the private health sector, reverse brain drain was evident. At the same time, foreign investors started to invest in the bankrupt private hospitals. Since 2001, the return of economic growth and the influx of foreign patients have started another round of internal brain drain.

  9. International service trade and its implications for human resources for health: a case study of Thailand

    Directory of Open Access Journals (Sweden)

    Pitayarangsarit Siriwan

    2004-06-01

    Full Text Available Abstract This study aims at analysing the impact of international service trade on the health care system, particularly in terms of human resources for health (HRH, using Thailand as a case study. Information was gathered through a literature review and interviews of relevant experts, as well as a brainstorming session. It was found that international service trade has greatly affected the Thai health care system and its HRH. From 1965 to 1975 there was massive emigration of physicians from Thailand in response to increasing demand in the United States of America. The country lost about 1,500 physicians, 20% of its total number, during that period. External migration of health professionals occurred without relation to agreements on trade in services. It was also found that free trade in service sectors other than health could seriously affect the health care system and HRH. Free trade in financial services with free flow of low-interest foreign loans, which started in 1993 in Thailand, resulted in the mushrooming of urban private hospitals between 1994 and 1997. This was followed by intensive internal migration of health professionals from rural public to urban private hospitals. After the economic crisis in 1997, with the resulting downturn of the private health sector, reverse brain drain was evident. At the same time, foreign investors started to invest in the bankrupt private hospitals. Since 2001, the return of economic growth and the influx of foreign patients have started another round of internal brain drain.

  10. Sonic Hedgehog activation is implicated in diosgenin-induced megakaryocytic differentiation of human erythroleukemia cells.

    Science.gov (United States)

    Ghezali, Lamia; Liagre, Bertrand; Limami, Youness; Beneytout, Jean-Louis; Leger, David Yannick

    2014-01-01

    Differentiation therapy is a means to treat cancer and is induced by different agents with low toxicity and more specificity than traditional ones. Diosgenin, a plant steroid, is able to induce megakaryocytic differentiation or apoptosis in human HEL erythroleukemia cells in a dose-dependent manner. However, the exact mechanism by which diosgenin induces megakaryocytic differentiation has not been elucidated. In this study, we studied the involvement of Sonic Hedgehog in megakaryocytic differentiation induced by diosgenin in HEL cells. First, we showed that different elements of the Hedgehog pathway are expressed in our model by qRT-PCR. Then, we focused our interest on key elements in the Sonic Hedgehog pathway: Smoothened receptor, GLI transcription factor and the ligand Sonic Hedgehog. We showed that Smoothened and Sonic Hedgehog were overexpressed in disogenin-treated cells and that GLI transcription factors were activated. Then, we showed that SMO inhibition using siSMO or the GLI antagonist GANT-61, blocked megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, we demonstrated that Sonic Hedgehog pathway inhibition led to inhibition of ERK1/2 activation, a major physiological pathway involved in megakaryocytic differentiation. In conclusion, our study reports, for the first time, a crucial role for the Sonic Hedgehog pathway in diosgenin-induced megakaryocytic differentiation in HEL cells.

  11. The hubs of the human connectome are generally implicated in the anatomy of brain disorders.

    Science.gov (United States)

    Crossley, Nicolas A; Mechelli, Andrea; Scott, Jessica; Carletti, Francesco; Fox, Peter T; McGuire, Philip; Bullmore, Edward T

    2014-08-01

    Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P brain disorders had lesions that were significantly more likely to be located in hubs (P human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

  12. In silico characterisation and chromosomal localisation of human RRH (peropsin – implications for opsin evolution

    Directory of Open Access Journals (Sweden)

    Foster Russell G

    2003-01-01

    Full Text Available Abstract Background The vertebrate opsins are proteins which utilise a retinaldehyde chromophore in their photosensory or photoisomerase roles in the visual/irradiance detection cycle. The majority of the opsins, such as rod and cone opsins, have a very highly conserved gene structure suggesting a common lineage. Exceptions to this are RGR-opsin and melanopsin, whose genes have very different intron insertion positions. The gene structure of another opsin, peropsin (retinal pigment epithelium-derived rhodopsin homologue, RRH is unknown. Results By in silico analysis of the GenBank database we have determined that the human RRH comprises 7 exons spanning approximately 16.5 kb and is localised to chromosome 4q25 in the following gene sequence: cen-EGF-RRH-IF-qter – a position that excludes this gene as a candidate for the RP29 autosomal recessive retinitis pigmentosa locus. A comparison of opsin gene structures reveals that RRH and RGR share two common intron (introns 1 and 4 insertion positions which may reflect a shared ancestral gene. Conclusion The opsins comprise a diverse group of genes which appear to have arisen from three different lineages. These lineages comprise the "classical opsin superfamily" which includes the rod and cone opsins, pinopsin, VA-opsin, parapinopsin and encephalopsin; the RRH and RGR group; and the melanopsin line. A common lineage for RRH and RGR, together with their sites of expression in the RPE, indicates that peropsin may act as a retinal isomerase.

  13. Emergence and evolutionary analysis of the human DDR network: implications in comparative genomics and downstream analyses.

    Science.gov (United States)

    Arcas, Aida; Fernández-Capetillo, Oscar; Cases, Ildefonso; Rojas, Ana M

    2014-04-01

    The DNA damage response (DDR) is a crucial signaling network that preserves the integrity of the genome. This network is an ensemble of distinct but often overlapping subnetworks, where different components fulfill distinct functions in precise spatial and temporal scenarios. To understand how these elements have been assembled together in humans, we performed comparative genomic analyses in 47 selected species to trace back their emergence using systematic phylogenetic analyses and estimated gene ages. The emergence of the contribution of posttranslational modifications to the complex regulation of DDR was also investigated. This is the first time a systematic analysis has focused on the evolution of DDR subnetworks as a whole. Our results indicate that a DDR core, mostly constructed around metabolic activities, appeared soon after the emergence of eukaryotes, and that additional regulatory capacities appeared later through complex evolutionary process. Potential key posttranslational modifications were also in place then, with interacting pairs preferentially appearing at the same evolutionary time, although modifications often led to the subsequent acquisition of new targets afterwards. We also found extensive gene loss in essential modules of the regulatory network in fungi, plants, and arthropods, important for their validation as model organisms for DDR studies.

  14. Human imprinting anomalies in fetal and childhood growth disorders: clinical implications and molecular mechanisms.

    Science.gov (United States)

    Azzi, Salah; Brioude, Fréderic; Le Bouc, Yves; Netchine, Irène

    2014-01-01

    Genomic imprinting is among the most important epigenetic mechanisms whereby expression of a subset of genes is restricted to a single parental allele. Loss of imprinting (LOI) through hypo or hyper methylation is involved in various human syndromes. These LOI occur early during development and usually impair growth. Some imprinting syndromes are the consequences of genetic anomalies, such as uniparental disomies (UPD) or copy number variations (deletion or duplications) involving the imprinted domains; others are due to LOI at the imprinting control regions (ICR) regulating each domain. Imprinting disorders are phenotypically heterogeneous, although some share various common clinical features such that diagnosis may be difficult. Multilocus imprinting defects associated with several syndromes have been increasingly reported in recent years, although there are no obvious clinical differences between monolocus and multilocus LOI patients. Subsequently, some rare mutations of transacting factors have been identified in patients with multilocus imprinting defects but they do not explain the majority of the cases; this therefore implies that other factors are involved. By contrast, no mutation of a transacting factor has yet been identified in monolocus LOI. The effect of the environment on the regulation of imprinting is clearly illustrated by studies of assisted reproductive technology (ART). The regulation of imprinting is complex and involves a huge range of genetic and environmental factors; the identification of these factors will undoubtedly help to elucidate the regulation of imprinting and contribute to the understanding of imprinting disorders. This would be beneficial for diagnostics, clinical follow up and the development of treatment guidelines.

  15. Redox proteomics identification of oxidatively modified myocardial proteins in human heart failure: implications for protein function.

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    Maura Brioschi

    Full Text Available Increased oxidative stress in a failing heart may contribute to the pathogenesis of heart failure (HF. The aim of this study was to identify the oxidised proteins in the myocardium of HF patients and analyse the consequences of oxidation on protein function. The carbonylated proteins in left ventricular tissue from failing (n = 14 and non-failing human hearts (n = 13 were measured by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated in the presence of stimuli relevant for HF in order to assess the generation of reactive oxygen species (ROS, the induction of protein carbonylation, and its consequences on protein function. The levels of carbonylated proteins were significantly higher in the HF patients than in the controls (p<0.01. We identified two proteins that mainly underwent carbonylation: M-type creatine kinase (M-CK, whose activity is impaired, and, to a lesser extent, α-cardiac actin. Exposure of cardiomyocytes to angiotensin II and norepinephrine led to ROS generation and M-CK carbonylation with loss of its enzymatic activity. Our findings indicate that protein carbonylation is increased in the myocardium during HF and that these oxidative changes may help to explain the decreased CK activity and consequent defects in energy metabolism observed in HF.

  16. Redox proteomics identification of oxidatively modified myocardial proteins in human heart failure: implications for protein function.

    Science.gov (United States)

    Brioschi, Maura; Polvani, Gianluca; Fratto, Pasquale; Parolari, Alessandro; Agostoni, Piergiuseppe; Tremoli, Elena; Banfi, Cristina

    2012-01-01

    Increased oxidative stress in a failing heart may contribute to the pathogenesis of heart failure (HF). The aim of this study was to identify the oxidised proteins in the myocardium of HF patients and analyse the consequences of oxidation on protein function. The carbonylated proteins in left ventricular tissue from failing (n = 14) and non-failing human hearts (n = 13) were measured by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated in the presence of stimuli relevant for HF in order to assess the generation of reactive oxygen species (ROS), the induction of protein carbonylation, and its consequences on protein function. The levels of carbonylated proteins were significantly higher in the HF patients than in the controls (p<0.01). We identified two proteins that mainly underwent carbonylation: M-type creatine kinase (M-CK), whose activity is impaired, and, to a lesser extent, α-cardiac actin. Exposure of cardiomyocytes to angiotensin II and norepinephrine led to ROS generation and M-CK carbonylation with loss of its enzymatic activity. Our findings indicate that protein carbonylation is increased in the myocardium during HF and that these oxidative changes may help to explain the decreased CK activity and consequent defects in energy metabolism observed in HF.

  17. Superficial aponeurosis of human gastrocnemius is elongated during contraction: implications for modeling muscle-tendon unit.

    Science.gov (United States)

    Muramatsu, Tadashi; Muraoka, Tetsuro; Kawakami, Yasuo; Fukunaga, Tetsuo

    2002-02-01

    Two questions were addressed in this study: (1) how much strain of the superficial aponeurosis of the human medial gastrocnemius muscle (MG) was obtained during voluntary isometric contractions in vivo, (2) whether there existed inhomogeneity of the strain along the superficial aponeurosis. Seven male subjects, whose knees were extended and ankles were flexed at right angle, performed isometric plantar flexion while elongation of superficial aponeurosis of MG was determined from the movements of the intersections made by the superficial aponeurosis and fascicles using ultrasonography. The strain of the superficial aponeurosis at the maximum voluntary contraction, estimated from the elongation and length data, was 5.6+/-1.2%. There was no significant difference in strain between the proximal and distal parts of the superficial aponeurosis. Based on the present result and that of our previous study for the same subjects (J. Appl. Physiol 90 (2001) 1671), a model was formulated for a contracting uni-pennate muscle-tendon unit. This model, which could be applied to isometric contractions at other angles and therefore of wide use, showed that similar strain between superficial and deep aponeuroses of MG contributed to homogeneous fascicle length change within MG during contractions. These findings would contribute to clarifying the functions of the superficial aponeurosis and the effects of the superficial aponeurosis elongation on the whole muscle behavior.

  18. Heavy Metal Distribution in Street Dust from Traditional Markets and the Human Health Implications.

    Science.gov (United States)

    Kim, Jin Ah; Park, Jin Hee; Hwang, Won Ju

    2016-08-13

    Street dust is a hazard for workers in traditional markets. Exposure time is longer than for other people, making them vulnerable to heavy metals in street dust. This study investigated heavy metal concentrations in street dust samples collected from different types of markets. It compared the results with heavy metal concentrations in heavy traffic and rural areas. Street dust was significantly enriched with most heavy metals in a heavy traffic area while street dust from a fish market was contaminated with cupper (Cu), lead (Pb) and zinc (Zn). Street dust from medicinal herb and fruit markets, and rural areas were not contaminated. Principal component and cluster analyses indicated heavy metals in heavy traffic road and fish market dust had different sources. Relatively high heavy metal concentration in street dust from the fish market may negatively affect worker's mental health, as depression levels were higher compared with workers in other markets. Therefore, intensive investigation of the relationship between heavy metal concentrations in street dust and worker's health in traditional marketplaces should be conducted to elucidate the effect of heavy metals on psychological health in humans.

  19. Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

    Science.gov (United States)

    Corbalan, J Jose; Medina, Carlos; Jacoby, Adam; Malinski, Tadeusz; Radomski, Marek W

    2012-01-01

    Background Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased number of studies indicate that this exposure may result in cardiovascular inflammation and damage. A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO−]) is crucial for cardiovascular homeostasis and platelet hemostasis. Therefore, we studied the influence of SiNP on the platelet [NO]/[ONOO−] balance and platelet aggregation. Methods Nanoparticle–platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO− released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy. Results Amorphous SiNP induced NO release from platelets followed by a massive stimulation of ONOO− leading to an unfavorably low [NO]/[ONOO−] ratio. In addition, SiNP induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size. Conclusions The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO−] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets. PMID:22334785

  20. Functional organization and its implication in evolution of the human protein-protein interaction network

    Directory of Open Access Journals (Sweden)

    Zhao Yiqiang

    2012-04-01

    Full Text Available Abstract Background Based on the distinguishing properties of protein-protein interaction networks such as power-law degree distribution and modularity structure, several stochastic models for the evolution of these networks have been purposed, motivated by the idea that a validated model should reproduce similar topological properties of the empirical network. However, being able to capture topological properties does not necessarily mean it correctly reproduces how networks emerge and evolve. More importantly, there is already evidence suggesting functional organization and significance of these networks. The current stochastic models of evolution, however, grow the network without consideration for biological function and natural selection. Results To test whether protein interaction networks are functionally organized and their impacts on the evolution of these networks, we analyzed their evolution at both the topological and functional level. We find that the human network is shown to be functionally organized, and its function evolves with the topological properties of the network. Our analysis suggests that function most likely affects local modularity of the network. Consistently, we further found that the topological unit is also the functional unit of the network. Conclusion We have demonstrated functional organization of a protein interaction network. Given our observations, we suggest that its significance should not be overlooked when studying network evolution.

  1. ELSI Bibliography: Ethical, legal and social implications of the Human Genome Project. 1994 Supplement

    Energy Technology Data Exchange (ETDEWEB)

    Yesley, M.S.; Ossorio, P.N. [comps.

    1994-09-01

    This report updates and expands the second edition of the ELSI Bibliography, published in 1993. The Bibliography and Supplement provides a comprehensive resource for identifying publications on the major topics related to the ethical, legal and social issues (ELSI) of the Human Genome Project. The Bibliography and Supplement are extracted from a database compiled at Los Alamos National Laboratory with the support of the Office of Energy Research, US Department of Energy. The second edition of the ELSI Bibliography was dated May 1993 but included publications added to the database until fall 1993. This Supplement reflects approximately 1,000 entries added to the database during the past year, bringing the total to approximately 7,000 entries. More than half of the new entries were published in the last year, and the remainder are earlier publications not previously included in the database. Most of the new entries were published in the academic and professional literature. The remainder are press reports from newspapers of record and scientific journals. The topical listing of the second edition has been followed in the Supplement, with a few changes. The topics of Cystic Fibrosis, Huntington`s Disease, and Sickle Cell Anemia have been combined in a single topic, Disorders. Also, all the entries published in the past year are included in a new topic, Publications: September 1993--September 1994, which provides a comprehensive view of recent reporting and commentary on the science and ELSI of genetics.

  2. Dietary Fiber Analysis of Four Pulses Using AOAC 2011.25: Implications for Human Health.

    Science.gov (United States)

    Chen, Yiran; McGee, Rebecca; Vandemark, George; Brick, Mark; Thompson, Henry J

    2016-12-21

    Chickpeas, common beans, dry peas, and lentils are pulse crops that have been a cornerstone of the human diet since the inception of agriculture. However, the displacement of pulses from the diet by low fiber protein alternatives has resulted in a pervasive deficiency referred to as the dietary fiber gap. Using an analytical method American Association of Analytical Chemists (AOAC) 2011.25 that conforms to the Codex Alimentarius Commission consensus definition for dietary fiber, the fiber content of these pulse crops was evaluated in seed types used for commercial production. These pulse crops have 2 to 3 times more fiber per 100 g edible portion than other dietary staples. Moreover, there is marked variation in fiber content among cultivars of the same crop. We conclude that pulse crop consumption should be emphasized in efforts to close the dietary fiber gap. The substantial differences in fiber content among currently available cultivars within a crop can be used to further improve gains in fiber intake without the need to change dietary habits. This provides a rationale for cultivar-based food labeling.

  3. Dietary Fiber Analysis of Four Pulses Using AOAC 2011.25: Implications for Human Health

    Directory of Open Access Journals (Sweden)

    Yiran Chen

    2016-12-01

    Full Text Available Chickpeas, common beans, dry peas, and lentils are pulse crops that have been a cornerstone of the human diet since the inception of agriculture. However, the displacement of pulses from the diet by low fiber protein alternatives has resulted in a pervasive deficiency referred to as the dietary fiber gap. Using an analytical method American Association of Analytical Chemists (AOAC 2011.25 that conforms to the Codex Alimentarius Commission consensus definition for dietary fiber, the fiber content of these pulse crops was evaluated in seed types used for commercial production. These pulse crops have 2 to 3 times more fiber per 100 g edible portion than other dietary staples. Moreover, there is marked variation in fiber content among cultivars of the same crop. We conclude that pulse crop consumption should be emphasized in efforts to close the dietary fiber gap. The substantial differences in fiber content among currently available cultivars within a crop can be used to further improve gains in fiber intake without the need to change dietary habits. This provides a rationale for cultivar-based food labeling.

  4. The impact of climate change and emissions control on future ozone levels: Implications for human health.

    Science.gov (United States)

    Stowell, Jennifer D; Kim, Young-Min; Gao, Yang; Fu, Joshua S; Chang, Howard H; Liu, Yang

    2017-11-01

    Overwhelming evidence has shown that, from the Industrial Revolution to the present, human activities influence ground-level ozone (O3) concentrations. Past studies demonstrate links between O3 exposure and health. However, knowledge gaps remain in our understanding concerning the impacts of climate change mitigation policies on O3 concentrations and health. Using a hybrid downscaling approach, we evaluated the separate impact of climate change and emission control policies on O3 levels and associated excess mortality in the US in the 2050s under two Representative Concentration Pathways (RCPs). We show that, by the 2050s, under RCP4.5, increased O3 levels due to combined climate change and emission control policies, could contribute to an increase of approximately 50 premature deaths annually nationwide in the US. The biggest impact, however, is seen under RCP8.5, where rises in O3 concentrations are expected to result in over 2,200 additional premature deaths annually. The largest increases in O3 are seen in RCP8.5 in the Northeast, the Southeast, the Central, and the West regions of the US. Additionally, when O3 increases are examined by climate change and emissions contributions separately, the benefits of emissions mitigation efforts may significantly outweigh the effects of climate change mitigation policies on O3-related mortality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Aberrant Phenotype in Human Endothelial Cells of Diabetic Origin: Implications for Saphenous Vein Graft Failure?

    Directory of Open Access Journals (Sweden)

    Anna C. Roberts

    2015-01-01

    Full Text Available Type 2 diabetes (T2DM confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC cultured from T2DM and nondiabetic (ND patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV- EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (~30% and angiogenesis (~40% compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp., effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium.

  6. Aberrant phenotype in human endothelial cells of diabetic origin: implications for saphenous vein graft failure?

    Science.gov (United States)

    Roberts, Anna C; Gohil, Jai; Hudson, Laura; Connolly, Kyle; Warburton, Philip; Suman, Rakesh; O'Toole, Peter; O'Regan, David J; Turner, Neil A; Riches, Kirsten; Porter, Karen E

    2015-01-01

    Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (~30%) and angiogenesis (~40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium.

  7. Sonic Hedgehog activation is implicated in diosgenin-induced megakaryocytic differentiation of human erythroleukemia cells.

    Directory of Open Access Journals (Sweden)

    Lamia Ghezali

    Full Text Available Differentiation therapy is a means to treat cancer and is induced by different agents with low toxicity and more specificity than traditional ones. Diosgenin, a plant steroid, is able to induce megakaryocytic differentiation or apoptosis in human HEL erythroleukemia cells in a dose-dependent manner. However, the exact mechanism by which diosgenin induces megakaryocytic differentiation has not been elucidated. In this study, we studied the involvement of Sonic Hedgehog in megakaryocytic differentiation induced by diosgenin in HEL cells. First, we showed that different elements of the Hedgehog pathway are expressed in our model by qRT-PCR. Then, we focused our interest on key elements in the Sonic Hedgehog pathway: Smoothened receptor, GLI transcription factor and the ligand Sonic Hedgehog. We showed that Smoothened and Sonic Hedgehog were overexpressed in disogenin-treated cells and that GLI transcription factors were activated. Then, we showed that SMO inhibition using siSMO or the GLI antagonist GANT-61, blocked megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, we demonstrated that Sonic Hedgehog pathway inhibition led to inhibition of ERK1/2 activation, a major physiological pathway involved in megakaryocytic differentiation. In conclusion, our study reports, for the first time, a crucial role for the Sonic Hedgehog pathway in diosgenin-induced megakaryocytic differentiation in HEL cells.

  8. CLINICAL IMPACT AND IMPLICATION OF HUMAN PAPILLOMAVIRUS (HPV IN CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Lilian Pustan

    2007-12-01

    Full Text Available The social and economic evolution of the world’s population in the last years has brought changes also in the prevalence of some diseases. Lately, viral infections have attracted specialists’ interest due to the unexpected complications they cause. Until not so long ago incriminated only for the development of warts, the Human papillomavirus infections have been found also to induce cellular abnormalities, such as the koilocytes, which in their turn indicate low grade squamous intraepithelial lesions (HSIL. According to the latest assessments worldwide, the HPV is responsible for 70% of the cervical cancer cases. The extensive research studies conducted by specialists came to know success when the HPV vaccines were launched on the market. In the summer of 2006, the first vaccine able to stop the expansion of HPV-induced cervical cancer came out, GARDASILTM, produced by Merck and Co., Whitehouse Station, New Jersey. It is a tetravalent vaccine (generates immunity against the oncogenic viral types 16 and 18, and the nononcogenic types 6 and 11. In our drugstores, one can find SILGARD, efficient and safe, providing 5-year protection, but not eradicating the effects of the viral infections acquired prior to vaccination. Apparition of the vaccine does not exclude cytological screening, which remains the most effective way to detect early a potential cancer of the cervix.

  9. Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress.

    Science.gov (United States)

    Wosu, Adaeze C; Valdimarsdóttir, Unnur; Shields, Alexandra E; Williams, David R; Williams, Michelle A

    2013-12-01

    Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis, and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, "cortisol," "hair," "confounders," "chronic," "stress," and "correlates." Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., post-traumatic stress disorder), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome), and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear not to be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies.

  10. Copy number polymorphism of the salivary amylase gene: implications in human nutrition research.

    Science.gov (United States)

    Santos, J L; Saus, E; Smalley, S V; Cataldo, L R; Alberti, G; Parada, J; Gratacòs, M; Estivill, X

    2012-01-01

    The salivary α-amylase is a calcium-binding enzyme that initiates starch digestion in the oral cavity. The α-amylase genes are located in a cluster on the chromosome that includes salivary amylase genes (AMY1), two pancreatic α-amylase genes (AMY2A and AMY2B) and a related pseudogene. The AMY1 genes show extensive copy number variation which is directly proportional to the salivary α-amylase content in saliva. The α-amylase amount in saliva is also influenced by other factors, such as hydration status, psychosocial stress level, and short-term dietary habits. It has been shown that the average copy number of AMY1 gene is higher in populations that evolved under high-starch diets versus low-starch diets, reflecting an intense positive selection imposed by diet on amylase copy number during evolution. In this context, a number of different aspects can be considered in evaluating the possible impact of copy number variation of the AMY1 gene on nutrition research, such as issues related to human diet gene evolution, action on starch digestion, effect on glycemic response after starch consumption, modulation of the action of α-amylases inhibitors, effect on taste perception and satiety, influence on psychosocial stress and relation to oral health.

  11. Morphological differentiation of aboriginal human populations from Tierra del Fuego (Patagonia): implications for South American peopling.

    Science.gov (United States)

    Perez, S Ivan; Bernal, Valeria; Gonzalez, Paula N

    2007-08-01

    This study aims to integrate the craniofacial morphological variation of southern South American populations with the results of mtDNA haplogroup variation, to discuss the South America peopling. Because the causes of morphological differentiation of Fueguian populations are still a controversial subject, the comparison with neutral variation could contribute to elucidate them. Samples of human remains from South America regions were used to analyze the evolutionary relationships. Several craniofacial traits observed in frontal and lateral view were analyzed by means of geometric morphometrics techniques, and the evolutionary relationships based on morphological and molecular data were established in base to ordination analyses. The results from the facial skeleton agree with those obtained from mtDNA haplogroup frequencies, with La Pampa/Chaco samples detached from the Patagonian samples. Hence, the same mechanism that accounts for the pattern of frequency of haplogroups could explain the variation found in facial skeleton among the samples. It is suggested that such geographic pattern of craniofacial and molecular diversity may reflect the effect of genetic drift that occurred in the small founding populations isolated by distance or geographic barriers. Conversely, the results obtained using the traits from the lateral view slightly differ from the molecular results, showing differences between southernmost Patagonian and the other samples. Therefore, mechanisms other than genetic drift (e.g., natural selection) could have acted to shape the pattern observed in some craniofacial structures present in the lateral view, characterized by the fact that the southernmost Patagonian samples display the most robust and dolichocephalic crania.

  12. The detection of cortisol in human sweat: implications for measurement of cortisol in hair.

    Science.gov (United States)

    Russell, Evan; Koren, Gideon; Rieder, Michael; Van Uum, Stan H M

    2014-02-01

    Hair cortisol analysis has been shown to be an effective measure of chronic stress. Cortisol is assumed to incorporate into hair via serum, sebum, and sweat sources; however, the extent to which sweat contributes to hair cortisol content is unknown. Sweat and saliva samples were collected from 17 subjects after a period of intensive exercise and analyzed by salivary enzyme-linked immunosorbent assay (ELISA). Subsequently, an in vitro test on exposure of hair to hydrocortisone was conducted. Residual hair samples were immersed in a 50-ng/mL hydrocortisone solution for periods lasting 15 minutes to 24 hours, followed by a wash or no-wash condition. Hair cortisol content was determined using our modified protocol for a salivary ELISA. Postexercise control sweat cortisol concentrations ranged from 8.16 to 141.7 ng/mL and correlated significantly with the log-transformed time of day. Sweat cortisol levels significantly correlated with salivary cortisol concentrations. In vitro hair exposure to a 50-ng/mL hydrocortisone solution (mimicking sweat) for 60 minutes or more resulted in significantly increased hair cortisol concentrations. Washing with isopropanol did not affect immersion-increased hair cortisol concentrations. Human sweat contains cortisol in concentrations comparable with salivary cortisol levels. This study suggests that perfuse sweating after intense exercise may increase cortisol concentrations detected in hair. This increase likely cannot be effectively decreased with conventional washing procedures and should be considered carefully in studies using hair cortisol as a biomarker of chronic stress.

  13. Correlates of Cortisol in Human Hair: Implications for Epidemiologic Studies on Health Effects of Chronic Stress

    Science.gov (United States)

    Wosu, Adaeze C.; Valdimarsdóttir, Unnur; Shields, Alexandra E.; Williams, David R.; Williams, Michelle A.

    2013-01-01

    Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, “cortisol” “hair” “confounders” “chronic” “stress” and “correlates.” Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., PTSD), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing´s syndrome) and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear to not be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies. PMID:24184029

  14. Effect of maternal diet on the epigenome: implications for human metabolic disease.

    Science.gov (United States)

    Lillycrop, Karen A

    2011-02-01

    The rapid increase in the incidence of chronic non-communicable diseases over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now considerable evidence that the fetal and early postnatal environment also strongly influences the risk of developing such diseases in later life. Human studies have shown that low birth weight is associated with an increased risk of CVD, type II diabetes, obesity and hypertension, although recent studies have shown that over-nutrition in early life can also increase susceptibility to future metabolic disease. These findings have been replicated in a variety of animal models, which have shown that both maternal under- and over-nutrition can induce persistent changes in gene expression and metabolism within the offspring. The mechanism by which the maternal nutritional environment induces such changes is beginning to be understood and involves the altered epigenetic regulation of specific genes. The demonstration of a role for altered epigenetic regulation of genes in the developmental induction of chronic diseases raises the possibility that nutritional or pharmaceutical interventions may be used to modify long-term cardio-metabolic disease risk and combat this rapid rise in chronic non-communicable diseases.

  15. Human Sperm Cryopreservation: Update on Techniques, Effect on DNA Integrity, and Implications for ART

    Directory of Open Access Journals (Sweden)

    Marlea Di Santo

    2012-01-01

    Full Text Available Cryopreservation of human spermatozoa—introduced in the 1960's—has been recognized as an efficient procedure for management of male fertility before therapy for malignant diseases, vasectomy or surgical infertility treatments, to store donor and partner spermatozoa before assisted reproduction treatments and to ensure the recovery of a small number of spermatozoa in severe male factor infertility. Despite the usefulness of it, cryopreservation may lead to deleterious changes of sperm structure and function: while the effects of cryopreservation on cells are well documented, to date there is no agreement in the literature on whether or not cryopreservation affects sperm chromatin integrity or on the use of a unique and functional protocol for the freezing-thawing procedure. Therefore, sperm cryopreservation is an important component of fertility management and much of its successful application seems to affect the reproductive outcome of assisted reproduction technologies (ART: appropriate use of cryoprotectants before and sperm selection technologies after cryopreservation seem to have the greatest impact on preventing DNA fragmentation, thus improving sperm cryosurvival rates.

  16. Assortative social learning and its implications for human (and animal?) societies.

    Science.gov (United States)

    Katsnelson, Edith; Lotem, Arnon; Feldman, Marcus W

    2014-07-01

    Choosing from whom to learn is an important element of social learning. It affects learner success and the profile of behaviors in the population. Because individuals often differ in their traits and capabilities, their benefits from different behaviors may also vary. Homophily, or assortment, the tendency of individuals to interact with other individuals with similar traits, is known to affect the spread of behaviors in humans. We introduce models to study the evolution of assortative social learning (ASL), where assorting on a trait acts as an individual-specific mechanism for filtering relevant models from which to learn when that trait varies. We show that when the trait is polymorphic, ASL may maintain a stable behavioral polymorphism within a population (independently of coexistence with individual learning in a population). We explore the evolution of ASL when assortment is based on a nonheritable or partially heritable trait, and when ASL competes with different non-ASL strategies: oblique (learning from the parental generation) and vertical (learning from the parent). We suggest that the tendency to assort may be advantageous in the context of social learning, and that ASL might be an important concept for the evolutionary theory of social learning.

  17. Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Gabriela Vilema-Enríquez

    2016-01-01

    Full Text Available Lung cancer has a very high mortality-to-incidence ratio, representing one of the main causes of cancer mortality worldwide. Therefore, new treatment strategies are urgently needed. Several diseases including lung cancer have been associated with the action of reactive oxygen species (ROS from which hydrogen peroxide (H2O2 is one of the most studied. Despite the fact that H2O2 may have opposite effects on cell proliferation depending on the concentration and cell type, it triggers several antiproliferative responses. H2O2 produces both nuclear and mitochondrial DNA lesions, increases the expression of cell adhesion molecules, and increases p53 activity and other transcription factors orchestrating cancer cell death. In addition, H2O2 facilitates the endocytosis of oligonucleotides, affects membrane proteins, induces calcium release, and decreases cancer cell migration and invasion. Furthermore, the MAPK pathway and the expression of genes related to inflammation including interleukins, TNF-α, and NF-κB are also affected by H2O2. Herein, we will summarize the main effects of hydrogen peroxide on human lung cancer leading to suggesting it as a potential therapeutic tool to fight this disease. Because of the multimechanistic nature of this molecule, novel therapeutic approaches for lung cancer based on the use of H2O2 may help to decrease the mortality from this malignancy.

  18. Human Development XIII: The Connection Between the Structure of the Overtone System and the Tone Language of Music. Some Implications for Our Understanding of the Human Brain

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2008-01-01

    Full Text Available The functioning brain behaves like one highly-structured, coherent, informational field. It can be popularly described as a “coherent ball of energy”, making the idea of a local highly-structured quantum field that carries the consciousness very appealing. If that is so, the structure of the experience of music might be a quite unique window into a hidden quantum reality of the brain, and even of life itself. The structure of music is then a mirror of a much more complex, but similar, structure of the energetic field of the working brain. This paper discusses how the perception of music is organized in the human brain with respect to the known tone scales of major and minor. The patterns used by the brain seem to be similar to the overtones of vibrating matter, giving a positive experience of harmonies in major. However, we also like the minor scale, which can explain brain patterns as fractal-like, giving a symmetric “downward reflection” of the major scale into the minor scale. We analyze the implication of beautiful and ugly tones and harmonies for the model. We conclude that when it comes to simple perception of harmonies, the most simple is the most beautiful and the most complex is the most ugly, but in music, even the most disharmonic harmony can be beautiful, if experienced as a part of a dynamic release of musical tension. This can be taken as a general metaphor of painful, yet meaningful, and developing experiences in human life.

  19. Ectoparasites and endoparasites of peridomestic house-rats in ile-ife, Nigeria and implication on human health.

    Directory of Open Access Journals (Sweden)

    Titus Ogunniyi

    2014-03-01

    Full Text Available There has never been a single case report of any parasitic zoonosis in Ile-Ife while just a case of human Acanthocephalan infection in Nigeria is available.Fifty (house-rats Rattus rattus (Linnaeus, 1758 were caught in houses and raw food sellers' stalls in a market in Ile-Ife. A caught rat was removed from the cage and sacrificed by cervical jerking. A rat was weighed, measured, quickly following which thick and thin blood films on microscope slides were made from blood collected from the tail vein. The rat was examined for ectoparasites then dissected to check for endoparasites.Two ectoparasites (Xenopsylla cheopis and Laelaptid mite were recovered from 19 (38.0% of the rats. Five genera of helminthes (Moniliformis, Hymenolepis, Taenia, Trichuris and Trichinella were recovered from 29 (58.0% of the rats while seven genera of protozoa organisms (Amoeba, Dientamoeba, Entamoeba, Retortamonas, Trichomonas, Chilomastix and Trypanosoma were recovered from 48 (96.0% of them. There was no correlation (Spearman's correlation coefficient = -0.111 between the weight of the individual rat and the total number of alimentary canal acquired parasites.In relation to human health, implications of the rats serving as reservoir hosts for the different pathogens are highlighted. In view of the possibility of unexpected zoonosis arising from the parasites found in the peridomestic rats in this investigation and others not found, and in view of the difficulties that may be associated with diagnosing such ailment, especially by a clinician who trained locally, this report should be like raising awareness to these salient facts.

  20. Infant formula and infant nutrition: bioactive proteins of human milk and implications for composition of infant formulas.

    Science.gov (United States)

    Lönnerdal, Bo

    2014-03-01

    Human milk contains an abundance of biologically active components that are highly likely to contribute to the short- and long-term benefits of breastfeeding. Many of these components are proteins; this article describes some of these proteins, such as α-lactalbumin, lactoferrin, osteopontin, and milk fat globule membrane proteins. The possibility of adding their bovine counterparts to infant formula is discussed as well as the implications for infant health and development. An important consideration when adding bioactive proteins to infant formula is that the total protein content of formula needs to be reduced, because formula-fed infants have significantly higher concentrations of serum amino acids, insulin, and blood urea nitrogen than do breastfed infants. When reducing the protein content of formula, the amino acid composition of the formula protein becomes important because serum concentrations of the essential amino acids should not be lower than those in breastfed infants. Both the supply of essential amino acids and the bioactivities of milk proteins are dependent on their digestibility: some proteins act only in intact form, others act in the form of larger or small peptides formed during digestion, and some are completely digested and serve as a source of amino acids. The purity of the proteins or protein fractions, potential contaminants of the proteins (such as lipopolysaccharide), as well as the degree of heat processing used during their isolation also need to be considered. It is likely that there will be more bioactive components added to infant formulas in the near future, but guidelines on how to assess their bioactivities in vitro, in animal models, and in clinical studies need to be established. The extent of testing needed is likely going to depend on the degree of complexity of the components and their bioequivalence with the human compounds whose effects they are intended to mimic.

  1. Molecular biology of human herpesvirus 8: novel functions and virus-host interactions implicated in viral pathogenesis and replication.

    Science.gov (United States)

    Cousins, Emily; Nicholas, John

    2014-01-01

    Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman's disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of "accessory" genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus-host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein-coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.

  2. Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals.

    Science.gov (United States)

    Jadcherla, Sudarshan R; Parks, Vanessa N; Peng, Juan; Dzodzomenyo, Samuel; Fernandez, Soledad; Shaker, Reza; Splaingard, Mark

    2012-01-01

    Electrocortical arousal (ECA) as an effect of visceral provocation or of its temporal relationships with aerodigestive reflexes in premature neonates is not known. We tested the hypothesis that esophageal provocation results in both esophageal reflex responses and ECAs during sleep and that ECAs are dependent on the frequency characteristics of esophageal neuromotor responses. We defined the spatiotemporal relationship of ECAs in relation to 1) spontaneous pharyngoesophageal swallow sequences and gastroesophageal reflux (GER) events and 2) sensory-motor characteristics of esophageal reflexes. Sixteen healthy premature neonates born at 27.9 ± 3.4 wk were tested at 36.8 ± 1.9 wk postmenstrual age. Ninety-five midesophageal and 31 sham stimuli were given in sleep during concurrent manometry and videopolysomnography. With stimulus onset as reference point, we scored the response latency, frequency occurrence and duration of arousals, peristaltic reflex, and upper esophageal sphincter contractile reflex (UESCR). Changes in polysomnography-respiratory patterns and esophageal sensory-motor parameters were scored by blinded observers. Significantly (for each characteristic listed, P reflexes or clearance, sleep state modification, and prolonged respiratory arousal. Midesophageal stimuli (54%) provoked arousals and were associated with increased frequency, prolonged latency, prolonged response duration of peristaltic reflexes and UESCR, and increased frequency of sleep state changes and respiratory arousals. In human neonates, ECAs are provoked upon esophageal stimulation; the sensory-motor characteristics of esophageal reflexes are distinct when accompanied by arousals. Aerodigestive homeostasis is defended by multiple tiers of aerodigestive safety mechanisms, and when esophageal reflexes are delayed, cortical hypervigilance (ECAs) occurs.

  3. Occurrence of parabens in foodstuffs from China and its implications for human dietary exposure.

    Science.gov (United States)

    Liao, Chunyang; Chen, Lingxin; Kannan, Kurunthachalam

    2013-07-01

    Parabens are alkyl esters of p-hydroxybenzoic acid and are used as antimicrobial preservatives in a range of consumer products, including cosmetics, pharmaceuticals, and foodstuffs. Despite their widespread use, prior to this study, paraben concentrations in foodstuffs from China and human dietary exposure to these chemicals have been unknown. In this study, concentrations of six parabens were determined in 13 categories of food samples (n=282), including cereals and cereal products, meat, fish and seafood, eggs, dairy products, bean products, fruits, vegetables, cookies, beverages, cooking oils, condiments, and others, collected from nine cities in China. Almost all (detection rate: 99%) food samples contained at least one of the parabens analyzed, and the total concentrations (ΣParabens; sum of six parabens) ranged from below limit of quantification (LOQ) to 2530ng/g fresh weight, with an overall mean value of 39.3ng/g. Methyl paraben (MeP), ethyl paraben (EtP), and propyl paraben (PrP) were the major paraben analogs found in foodstuffs, and these compounds accounted for 59%, 24%, and 10%, respectively, of ΣParaben concentrations. Although the mean concentrations of ΣParabens varied among different categories of food items (from 0.839ng/g in beverages to 100ng/g in vegetables), the concentrations were not statistically significant among the 13 food categories, including canned foodstuffs. Estimated daily intake (EDI) of parabens was based on the measured concentrations in foods and the corresponding daily food ingestion rates. The mean and 95th percentile values for EDI were 1010 and 3040ng/kg body weight (bw)/day for adult men and 1060 and 3170ng/kg bw/day for adult women, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

    2010-12-01

    Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [{sup 11}C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight {approx}1246 g), liver (23%; weight {approx}1677 g) and intermediate in brain (10%; weight {approx}1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [{sup 11}C]d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

  5. Human Enteroviruses isolated during acute flaccid paralysis surveillance in Ghana: implications for the post eradication era.

    Science.gov (United States)

    Odoom, John Kofi; Obodai, Evangeline; Barnor, Jacob Samson; Ashun, Miriam; Arthur-Quarm, Jacob; Osei-Kwasi, Mubarak

    2012-01-01

    Surveillance of acute flaccid surveillance (AFP) has been used world-wide to monitor the control and eradication of circulating wild polioviruses. The Polio Laboratory since its accreditation in 1996 has supported the Disease Surveillance Department for AFP surveillance. This study aims to isolate and characterize human enteroviruses from patients with AFP in Ghana. Stool suspension was prepared from 308 samples received in 2009 from the surveillance activities throughout the country and inoculated on both RD and L20B cell lines. Isolates that showed growth on L20B were selected for real-time RT-PCR using degenerate and non-degenerate primers and probes. RD isolates were however characterized by microneutralisation technique with antisera pools from RIVM, The Netherlands and viruses that were untypable subjected to neutralization assay using antibodies specific for E71. Of the 308 samples processed, 17 (5.5%) grew on both L20B and RD cells while 32 (10.4%) grew on RD only. All 28 isolates from L20B were characterized by rRT-PCR as Sabin-like polioviruses. No wild poliovirus or VDPV was found. However from the microneutralisation assay, six different enteroviruses were characterized. Among these, Coxsackie B viruses were most predominant followed by Echovirus. Three children from whom non-polio enteroviruses were isolated had residual paralysis while one child with VAPP found. The non-polio enteroviruses circulated throughout the country with the majority (20.7%) from Ashanti region. This study showed the absence of wild or vaccine-derived poliovirus circulation in the country. However, the detection of three non-polio enteroviruses and one Sabin-like poliovirus with residual paralysis call for continuous surveillance even in the post polio eradication era.

  6. Air Quality, Human Health and Climate Implications of China's Synthetic Natural Gas Development

    Science.gov (United States)

    Qin, Y.; Mauzerall, D. L.; Wagner, F.; Smith, K. R.; Peng, W.; Yang, J.; Zhu, T.

    2016-12-01

    Facing severe air pollution and growing dependence on natural gas imports, the Chinese government is planning an enormous increase in synthetic natural gas (SNG) production. Although displacement of coal with SNG benefits air quality, it increases carbon dioxide (CO2) emissions and thus worsens climate change. Primarily due to variation in air pollutant and CO2 emission factors as well as energy efficiencies across sectors and regions, the replacement of coal with SNG results in varying degrees of air quality and adverse climate impacts. Here we conduct an integrated assessment to estimate the air quality, human health, and adverse climate impacts of various sectoral and regional SNG substitution strategies for coal in China in 2020. We find that using all planned production of SNG in the residential sector results in an annual decrease of approximately 43,000 (22,000 to 63,000) outdoor-air-pollution-associated Chinese premature mortalities, with ranges determined by the low and high estimates of relative risks. If changes in indoor/household air pollution were also included the decrease would be larger. By comparison, this is a 10 and 60 times greater reduction in premature mortalities than obtained when the SNG displaces coal in the industrial or power sectors, respectively. Deploying SNG as a coal replacement in the industrial or power sectors also has a 4-5 times higher carbon penalty than utilization in the residential sector due to inefficiencies in current household coal use. If carbon capture and storage (CCS) is used in SNG production, substituting SNG for coal can provide both air quality and climate co-benefits in all scenarios. However, even with CCS, SNG emits 22-40% (depending on end-use) more CO2 than the same amount of conventional gas. For existing SNG projects, we find displacing coal with SNG in the residential sector provides the largest air quality and health benefits with the smallest carbon penalties of deployment in any sector.

  7. Multifunctional liposomes interact with Abeta in human biological fluids: Therapeutic implications for Alzheimer's disease.

    Science.gov (United States)

    Conti, Elisa; Gregori, Maria; Radice, Isabella; Da Re, Fulvio; Grana, Denise; Re, Francesca; Salvati, Elisa; Masserini, Massimo; Ferrarese, Carlo; Zoia, Chiara Paola; Tremolizzo, Lucio

    2017-02-23

    The accumulation of extracellular amyloid beta (Abeta42) both in brain and in cerebral vessels characterizes Alzheimer's disease (AD) pathogenesis. Recently, the possibility to functionalize nanoparticles (NPs) surface with Abeta42 binding molecules, making them suitable tools for reducing Abeta42 burden has been shown effective in models of AD. Aim of this work consisted in proving that NPs might be effective in sequestering Abeta42 in biological fluids, such as CSF and plasma. This demonstration is extremely important considering that these Abeta42 pools are in continuum with the brain parenchyma with drainage of Abeta from interstitial brain tissue to blood vessel and plasma. In this work, liposomes (LIP) were functionalized as previously shown in order to promote high-affinity Abeta binding, i.e., either with, phosphatidic acid (PA), or a modified Apolipoprotein E-derived peptide (mApo), or with a curcumin derivative (TREG); Abeta42 levels were determined by ELISA in CSF and plasma samples. mApo-PA-LIP (25 and 250 μM) mildly albeit significantly sequestered Abeta42 proteins in CSF samples obtained from healthy subjects (p < 0.01). Analogously a significant binding (∼20%) of Abeta42 (p < 0.001) was demonstrated following exposure to all functionalized liposomes in plasma samples obtained from selected AD or Down's syndrome patients expressing high levels of Abeta42. The same results were obtained by quantifying Abeta42 content after removal of liposome-bound Abeta by using gel filtration chromatography or ultracentrifugation on a discontinuous sucrose density gradient. In conclusion, we demonstrate that functionalized liposomes significantly sequester Abeta42 in human biological fluids. These data may be critical for future in vivo administration tests using NPs for promoting sink effect.

  8. [Effects of lead exposure on the human body and health implications].

    Science.gov (United States)

    Moreira, Fátima Ramos; Moreira, Josino Costa

    2004-02-01

    To review the literature concerning the risks associated with exposure to lead and lead compounds, especially in children and in populations that are occupationally exposed. Using "chumbo" [lead] and "efeitos" [effects] as search terms, two large databases, namely PubMed (United States National Library of Medicine) and LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde [Latin American and Caribbean Literature in the Health Sciences]), were searched for studies on lead toxicity from 1988 to 2002. Other sources used to conduct the search include the web page of the United States Agency for Toxic Substances and Disease Registry, in Atlanta, Georgia, and the library of the Toxicology Laboratory of the Center for Workers' Health and Human Ecology at the National School of Public Health [Centro de Estudos da Saúde de Trabalhador e Ecologia Humana, Escola Nacional de Saúde Pública], Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. The toxic effects of lead and lead compounds have been extensively studied for over a century. In recent years, epidemiologic studies have focused primarily on the neurotoxic effects of lead on children, particularly in terms of impaired intellectual ability and behavioral problems. However, there is still insufficient information on the mechanisms of action that account for such toxicity. More in-depth studies are also needed on the effects of lead exposure on bone, the central nervous system, the cardiovascular system, the kidneys, the liver, the male and female reproductive systems, and the endocrine system. The potential teratogenicity and carcinogenicity of lead, as well as its effect on pregnancy outcomes and neonatal growth and development, also require further study.

  9. Investigation of the mechanical properties of the human crural fascia and their possible clinical implications.

    Science.gov (United States)

    Stecco, Carla; Pavan, Piero; Pachera, Paola; De Caro, Raffaele; Natali, Arturo

    2014-01-01

    The mechanical properties of deep fasciae strongly affect muscular actions, development of pathologies, such as acute and chronic compartment syndromes, and the choice of the various fascial flaps. Actually, a clear knowledge of the mechanical characterization of these tissues still lacks. This study focuses attention on experimental tests of different regions of human crural fascia taken from an adult frozen donor. Tensile tests along proximal-distal and medial-lateral direction at a strain rate of 120 %/s were performed at the purpose of evaluating elastic properties. Viscous phenomena were investigated by applying incremental relaxation tests at total strain of 7, 9 and 11 % and observing stress decay for a time interval of 240 s. The elastic response showed that the fascia in the anterior compartment is stiffer than in the posterior compartment, both along the proximal-distal and medial-lateral directions. This result can explain why the compartment syndromes are more frequent in this compartment with respect to posterior one. Furthermore, the fascia is stiffer along the proximal-distal than along medial-lateral direction. This means that the crural fascia can adapt to the muscular variation of volume in a transversal direction, while along the main axis it could be considered as a structure that contributes to transmitting the muscular forces at a distance and connecting the different segments of the limb. The stress relaxation tests showed that the crural fascia needs 120 s to decrease stress of 40 %, suggesting a similar time also in the living so that the static stretching could have an effect on the fascia.

  10. Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells.

    Science.gov (United States)

    Cailleteau, C; Liagre, B; Battu, S; Jayat-Vignoles, C; Beneytout, J L

    2008-09-01

    Differentiation induction as a therapeutic strategy has, so far, the greatest impact in hematopoietic malignancies, most notably leukemia. Diosgenin is a very interesting natural product because, depending on the specific dose used, its biological effect is very different in HEL (human erythroleukemia) cells. For example, at 10 microM, diosgenin induced megakaryocytic differentiation, in contrast to 40 microM diosgenin, which induced apoptosis in HEL cells previously demonstrated using sedimentation field-flow fractionation (SdFFF). The goal of this work focused on the correlation between cyclooxygenase-2 (COX-2) and thromboxane synthase (TxS) and megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, the technique of SdFFF, having been validated in our models, was used in this new study as an analytical tool that provided us with more or less enriched differentiated cell fractions that could then be used for further analyses of enzyme protein expression and activity for the first time. In our study, we showed the implication of COX-2 and TxS in diosgenin-induced megakaryocytic differentiation in HEL cells. Furthermore, we showed that the analytical technique of SdFFF may be used as a tool to confirm our results as a function of the degree of cell differentiation.

  11. Implication of limonene and linalyl acetate in cytotoxicity induced by bergamot essential oil in human neuroblastoma cells.

    Science.gov (United States)

    Russo, Rossella; Ciociaro, Antonella; Berliocchi, Laura; Cassiano, Maria Gilda Valentina; Rombolà, Laura; Ragusa, Salvatore; Bagetta, Giacinto; Blandini, Fabio; Corasaniti, Maria Tiziana

    2013-09-01

    Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a widely used plant extract showing anxiolytic, analgesic and neuroprotective effects in rodents; also, BEO activates multiple death pathways in cancer cells. Despite detailed knowledge of its chemical composition, the constituent/s responsible for these pharmacological activities remain largely unknown. Aim of the present study was to identify the components of BEO implicated in cell death. To this end, limonene, linalyl acetate, linalool, γ-terpinene, β-pinene and bergapten were individually tested in human SH-SY5Y neuroblastoma cultures at concentrations comparable with those found in cytotoxic dilutions of BEO. None of the tested compounds elicited cell death. However, significant cytotoxicity was observed when cells were cotreated with limonene and linalyl acetate whereas no other associations were effective. Only cotreatment, but not the single exposure to limonene and linalyl acetate, replicated distinctive morphological and biochemical changes induced by BEO, including caspase-3 activation, PARP cleavage, DNA fragmentation, cell shrinkage, cytoskeletal alterations, together with necrotic and apoptotic cell death. Collectively, our findings suggest a major role for a combined action of these monoterpenes in cancer cell death induced by BEO.

  12. Combining spatial distribution with oral bioaccessibility of metals in smelter-impacted soils: implications for human health risk assessment.

    Science.gov (United States)

    Pelfrêne, Aurélie; Détriché, Sébastien; Douay, Francis

    2015-02-01

    Geostatistical analysis and GIS-based spatial mapping have been widely used for risk assessment of environmental pollution. The objectives of this study were to: (1) investigate the spatial variability of pseudototal concentrations of Cd, Pb, and Zn; (2) estimate the degree of contamination on the basis of pollution indexes; and (3) combine geostatistical analysis with oral bioaccessibility to better assess the population's exposure to metals in smelter-impacted soils. Implications for human health risks were assessed by considering soil as a contaminant source, a release mechanism of contaminated soil to the hands, ingestion as an exposure route, and metal bioaccessibility. The bioaccessibility data in the gastric (G) and gastrointestinal (GI) phases were integrated into the standard hazard quotient-based risk assessment method. Using pollution indices showed that the entire area studied was highly polluted in terms of soil metal concentrations. However, the spatial pattern of health risk levels did not coincide with the spatial distribution of the degree of soil contamination. Introducing the bioaccessible fraction of metals from soils into the exposure calculations resulted in a substantial decrease in calculated risk (HI, hazard inde