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Sample records for human septins implications

  1. A draft of the human septin interactome.

    Directory of Open Access Journals (Sweden)

    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. The septins

    National Research Council Canada - National Science Library

    Hall, Peter A; Russell, S.E. Hilary; Pringle, John R

    2008-01-01

    ... and Caenorhabditis elegans Christine M. Field, Amy Shaub Maddox, John R. Pringle and Karen Oegema 147 Section III Septins in mammals 169 Chapter 7 The genomics and regulation of the human septin genes S.E....

  3. Crystallization and preliminary crystallographic studies of human septin 1 with site-directed mutations

    International Nuclear Information System (INIS)

    Hu, Hao; Yu, Wen-bo; Li, Shu-xing; Ding, Xiang-ming; Yu, Long; Bi, Ru-Chang

    2006-01-01

    The homogeneity of septin 1 has been improved by site-directed mutation of serine residues and only a small alteration in the secondary structure is observed to arise from the mutations. Crystals of the septin 1 mutant were grown and diffraction data were collected to 2.5 Å resolution. Septin 1 is a member of an evolutionarily conserved family of GTP-binding and filament-forming proteins named septins, which function in diverse processes including cytokinasis, vesicle trafficking, apoptosis, remodelling of the cytoskeleton, infection, neurodegeneration and neoplasia. Human septin 1 has been expressed and purified, but suffers from severe aggregation. Studies have shown that septin 1 with site-directed mutations of five serine residues (Ser19, Ser206, Ser307, Ser312 and Ser315) has a much lower degree of aggregation and better structural homogeneity and that the mutations cause only slight perturbations in the secondary structure of septin 1. This septin 1 mutant was crystallized and diffraction data were collected to 2.5 Å resolution. The space group is P422, with unit-cell parameters a = b = 106.028, c = 137.852 Å

  4. Crystallization and preliminary crystallographic studies of human septin 1 with site-directed mutations

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    Hu, Hao [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Yu, Wen-bo [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433 (China); Li, Shu-xing [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Ding, Xiang-ming; Yu, Long [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433 (China); Bi, Ru-Chang [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2006-02-01

    The homogeneity of septin 1 has been improved by site-directed mutation of serine residues and only a small alteration in the secondary structure is observed to arise from the mutations. Crystals of the septin 1 mutant were grown and diffraction data were collected to 2.5 Å resolution. Septin 1 is a member of an evolutionarily conserved family of GTP-binding and filament-forming proteins named septins, which function in diverse processes including cytokinasis, vesicle trafficking, apoptosis, remodelling of the cytoskeleton, infection, neurodegeneration and neoplasia. Human septin 1 has been expressed and purified, but suffers from severe aggregation. Studies have shown that septin 1 with site-directed mutations of five serine residues (Ser19, Ser206, Ser307, Ser312 and Ser315) has a much lower degree of aggregation and better structural homogeneity and that the mutations cause only slight perturbations in the secondary structure of septin 1. This septin 1 mutant was crystallized and diffraction data were collected to 2.5 Å resolution. The space group is P422, with unit-cell parameters a = b = 106.028, c = 137.852 Å.

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

    International Nuclear Information System (INIS)

    Juvvadi, Praveen Rao; Belina, Detti; Soderblom, Erik J.; Moseley, M. Arthur; Steinbach, William J.

    2013-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-15

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

  7. Septin functions in organ system physiology and pathology.

    Science.gov (United States)

    Dolat, Lee; Hu, Qicong; Spiliotis, Elias T

    2014-02-01

    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.

  8. Single-nucleotide polymorphisms in the SEPTIN12 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

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    Miyakawa, Hiroe; Miyamoto, Toshinobu; Koh, Eitetsu; Tsujimura, Akira; Miyagawa, Yasushi; Saijo, Yasuaki; Namiki, Mikio; Sengoku, Kazuo

    2012-01-01

    Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis, including human SEPTIN12, were identified by expression microarray analysis of human testicular tissue. Septin12 is a member of the septin family of conserved cytoskeletal GTPases that form heteropolymeric filamentous structures in interphase cells. It is expressed specifically in the testis. Therefore, we hypothesized that mutation or polymorphisms of SEPTIN12 participate in male infertility, especially Sertoli cell-only syndrome (SCOS). To investigate whether SEPTIN12 gene defects are associated with azoospermia caused by SCOS, mutational analysis was performed in 100 Japanese patients by direct sequencing of coding regions. Statistical analysis was performed in patients with SCOS and in 140 healthy control men. No mutations were found in SEPTIN12 ; however, 8 coding single-nucleotide polymorphisms (SNP1-SNP8) could be detected in the patients with SCOS. The genotype and allele frequencies in SNP3, SNP4, and SNP6 were notably higher in the SCOS group than in the control group (P < .001). These results suggest that SEPTIN12 might play a critical role in human spermatogenesis.

  9. Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast.

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    Johnson, Courtney R; Weems, Andrew D; Brewer, Jennifer M; Thorner, Jeremy; McMurray, Michael A

    2015-04-01

    Septin hetero-oligomers polymerize into cytoskeletal filaments with essential functions in many eukaryotic cell types. Mutations within the oligomerization interface that encompasses the GTP-binding pocket of a septin (its "G interface") cause thermoinstability of yeast septin hetero-oligomer assembly, and human disease. When coexpressed with its wild-type counterpart, a G interface mutant is excluded from septin filaments, even at moderate temperatures. We show that this quality control mechanism is specific to G interface mutants, operates during de novo septin hetero-oligomer assembly, and requires specific cytosolic chaperones. Chaperone overexpression lowers the temperature permissive for proliferation of cells expressing a G interface mutant as the sole source of a given septin. Mutations that perturb the septin G interface retard release from these chaperones, imposing a kinetic delay on the availability of nascent septin molecules for higher-order assembly. Un-expectedly, the disaggregase Hsp104 contributes to this delay in a manner that does not require its "unfoldase" activity, indicating a latent "holdase" activity toward mutant septins. These findings provide new roles for chaperone-mediated kinetic partitioning of non-native proteins and may help explain the etiology of septin-linked human diseases. © 2015 Johnson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

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

    African Journals Online (AJOL)

    Purpose: To examine septin 9 gene-promoter methylation content in colorectal cancer and establish its significance in cancer progression and chemoresistance. Methods: Patient samples and colorectal cancer cell lines (CRC) were evaluated for septin 9 expression and promoter hypermethylation content. Septin 9 ...

  11. Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

    Energy Technology Data Exchange (ETDEWEB)

    Wasik, Anita A.; Dumont, Vincent [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Tienari, Jukka [Department of Pathology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, 05850 Hyvinkää (Finland); Nyman, Tuula A. [Institute of Biotechnology, University of Helsinki, 00014 Helsinki (Finland); Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Lehtonen, Eero [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland); Laboratory Animal Centre, University of Helsinki, 00014 Helsinki (Finland); Groop, Per-Henrik [Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki (Finland); Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 000290 Helsinki (Finland); Diabetes& Obesity Research Program, Research Program´s Unit, 00014 University of Helsinki (Finland); Baker IDI Heart & Diabetes Institute, 3004 Melbourne (Australia); Lehtonen, Sanna, E-mail: sanna.h.lehtonen@helsinki.fi [Department of Pathology, University of Helsinki, 00014 Helsinki (Finland)

    2017-01-15

    Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

  12. Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

    International Nuclear Information System (INIS)

    Wasik, Anita A.; Dumont, Vincent; Tienari, Jukka; Nyman, Tuula A.; Fogarty, Christopher L.; Forsblom, Carol; Lehto, Markku; Lehtonen, Eero; Groop, Per-Henrik; Lehtonen, Sanna

    2017-01-01

    Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.

  13. 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.

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

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    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.

  15. Regulation of calretinin in malignant mesothelioma is mediated by septin 7 binding to the CALB2 promoter.

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    Blum, Walter; Pecze, László; Rodriguez, Janine Wörthmüller; Steinauer, Martine; Schwaller, Beat

    2018-04-27

    revealed this co-localization to be the result of a direct interaction between calretinin and septin 7. Our results demonstrate septin 7 not only serving as a "cytoskeletal" protein, but also as a transcription factor repressing calretinin expression. The negative regulation of calretinin by septin 7 and vice versa sheds new light on mechanisms possibly implicated in MM formation and identifies these proteins as transcriptional regulators and putative targets for MM therapy.

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

    African Journals Online (AJOL)

    radiotherapy and chemotherapy are widely used but its outcomes are ... Multiple studies have shown that septin 9 gene spanning a region of 219 kb in the genome and encoding different ... suggested a tumor-suppressor role [10]. Despite.

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

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    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.

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

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    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. A Septin-Dependent Diffusion Barrier at Dendritic Spine Necks.

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    Helge Ewers

    Full Text Available Excitatory glutamatergic synapses at dendritic spines exchange and modulate their receptor content via lateral membrane diffusion. Several studies have shown that the thin spine neck impedes the access of membrane and solute molecules to the spine head. However, it is unclear whether the spine neck geometry alone restricts access to dendritic spines or if a physical barrier to the diffusion of molecules exists. Here, we investigated whether a complex of septin cytoskeletal GTPases localized at the base of the spine neck regulates diffusion across the spine neck. We found that, during development, a marker of the septin complex, Septin7 (Sept7, becomes localized to the spine neck where it forms a stable structure underneath the plasma membrane. We show that diffusion of receptors and bulk membrane, but not cytoplasmic proteins, is slower in spines bearing Sept7 at their neck. Finally, when Sept7 expression was suppressed by RNA interference, membrane molecules explored larger membrane areas. Our findings indicate that Sept7 regulates membrane protein access to spines.

  20. 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.

  1. The step-wise pathway of septin hetero-octamer assembly in budding yeast.

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    Weems, Andrew; McMurray, Michael

    2017-05-25

    Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended Cdc3 N terminus autoinhibits Cdc3 association with Cdc10 homodimers until prior Cdc3-Cdc12 interaction. Slow hydrolysis by monomeric Cdc12 and specific affinity of Cdc11 for transient Cdc12•GTP drive assembly of distinct trimers, Cdc11-Cdc12-Cdc3 or Shs1-Cdc12-Cdc3. Decreasing the cytosolic GTP:GDP ratio increases the incorporation of Shs1 vs Cdc11, which alters the curvature of filamentous septin rings. Our findings explain how GTP hydrolysis controls septin assembly, and uncover mechanisms by which cells construct defined septin complexes.

  2. Sep(t)arate or not – how some cells take septin-independent routes through cytokinesis.

    Science.gov (United States)

    Menon, Manoj B; Gaestel, Matthias

    2015-05-15

    Cytokinesis is the final step of cell division, and is a process that requires a precisely coordinated molecular machinery to fully separate the cytoplasm of the parent cell and to establish the intact outer cell barrier of the daughter cells. Among various cytoskeletal proteins involved, septins are known to be essential mediators of cytokinesis. In this Commentary, we present recent observations that specific cell divisions can proceed in the absence of the core mammalian septin SEPT7 and its Drosophila homolog Peanut (Pnut) and that thus challenge the view that septins have an essential role in cytokinesis. In the pnut mutant neuroepithelium, orthogonal cell divisions are successfully completed. Similarly, in the mouse, Sept7-null mutant early embryonic cells and, more importantly, planktonically growing adult hematopoietic cells undergo productive proliferation. Hence, as discussed here, mechanisms must exist that compensate for the lack of SEPT7 and the other core septins in a cell-type-specific manner. Despite there being crucial non-canonical immune-relevant functions of septins, septin depletion is well tolerated by the hematopoietic system. Thus differential targeting of cytokinesis could form the basis for more specific anti-proliferative therapies to combat malignancies arising from cell types that require septins for cytokinesis, such as carcinomas and sarcomas, without impairing hematopoiesis that is less dependent on septin. © 2015. Published by The Company of Biologists Ltd.

  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...

  4. Implications of human tissue studies

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1986-10-01

    Through radiochemical analysis of voluntary tissue donations, the United States Transuranium and Uranium Registries are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole body contributions to the Transuranium Registry revealed an inverse proportionality between actinide concentration and bone ash fraction. The analysis of a whole body with a documented 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies of the Registries are designed to evaluate in vivo estimates of actinide deposition with those derived from postmortem tissue analysis, compare results of animal experiments with human data, and reviw histopathologic slides for tissue toxicity that might be attributable to exposure to uranium and the transuranic elements. The implications of these recent findings and other work of the Registries are discussed from the standpoint of their potential impact on biokinetic modeling, internal dose assessment, safety standards, and operational health physics practices

  5. Single nucleotide polymorphisms in the SEPTIN12 gene may be associated with azoospermia by meiotic arrest in Japanese men.

    Science.gov (United States)

    Miyamoto, Toshinobu; Tsujimura, Akira; Miyagawa, Yasushi; Koh, Eitetsu; Namiki, Mikio; Horikawa, Michiharu; Saijo, Yasuaki; Sengoku, Kazuo

    2012-01-01

    To investigate the association between SEPTIN12 gene variants and the risk of azoospermia caused by meiotic arrest. Mutational analysis of the SEPTIN12 gene was performed using DNA from 30 Japanese patients with azoospermia by meiotic arrest and 140 fertile male controls. The frequencies of the c.204G>C (Gln38His) allele and the CC genotype were significantly higher in patients than in fertile controls (p C (Gln38His) variant in the SEPTIN12 gene was associated with increased susceptibility to azoospermia caused by meiotic arrest.

  6. 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. © 2014 AWHONN.

  7. Forging the ring: from fungal septins' divergent roles in morphology, septation and virulence to factors contributing to their assembly into higher order structures.

    Science.gov (United States)

    Vargas-Muñiz, Jose M; Juvvadi, Praveen R; Steinbach, William J

    2016-09-01

    Septins are a conserved family of GTP-binding proteins that are distributed across different lineages of the eukaryotes, with the exception of plants. Septins perform a myriad of functions in fungal cells, ranging from controlling morphogenetic events to contributing to host tissue invasion and virulence. One key attribute of the septins is their ability to assemble into heterooligomeric complexes that organizse into higher order structures. In addition to the established role of septins in the model budding yeast, Saccharomyces cerevisiae, their importance in other fungi recently emerges. While newer roles for septins are being uncovered in these fungi, the mechanism of how septins assemble into a complex and their regulation is only beginning to be comprehended. In this review, we summarize recent findings on the role of septins in different fungi and focus on how the septin complexes of different fungi are organized in vitro and in vivo. Furthermore, we discuss on how phosphorylation/dephosphorylation can serve as an important mechanism of septin complex assembly and regulation.

  8. Cultural Implications of Human Resource Development.

    Science.gov (United States)

    Hiranpruk, Chaiskran

    A discussion of the cultural effects of economic and, by extension, human resource development in Southeast Asia looks at short- and long-term implications. It is suggested that in the short term, increased competition will affect distribution of wealth, which can promote materialism and corruption. The introduction of labor-saving technology may…

  9. Septin-Containing Barriers Control the Differential Inheritance of Cytoplasmic Elements

    Directory of Open Access Journals (Sweden)

    Alan Michael Tartakoff

    2013-01-01

    Full Text Available Fusion of haploid cells of Saccharomyces cerevisiae generates zygotes. We observe that the zygote midzone includes a septin annulus and differentially affects redistribution of supramolecular complexes and organelles. Redistribution across the midzone of supramolecular complexes (polysomes and Sup35p-GFP [PSI+] is unexpectedly delayed relative to soluble proteins; however, in [psi-] × [PSI+] crosses, all buds eventually receive Sup35p-GFP [PSI+]. Encounter between parental mitochondria is further delayed until septins relocate to the bud site, where they are required for repolarization of the actin cytoskeleton. This delay allows rationalization of the longstanding observation that terminal zygotic buds preferentially inherit a single mitochondrial genotype. The rate of redistribution of complexes and organelles determines whether their inheritance will be uniform.

  10. 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.

  11. 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.

  12. Implications of global warming on human health

    International Nuclear Information System (INIS)

    Singh, R.K.; Syam, P.V.S.

    1997-01-01

    Due to the build up of green house gases in atmosphere, less heat escapes through the atmosphere promoting global warming. This may result in world wide droughts, sea-level rise inundating islands and coastal countries, cataclysmic hurricanes etc. Human health as a result of these changes, will be affected both physiologically and psychologically. Physiological effects may be more pronounced in cases occurring due to changes in rainfall and temperature patterns, food production amounts, water availability, etc. Psychological impact may be more in cases of catastrophes like floods, hurricanes or famine. In this paper, an attempt has been made to highlight the implications of global warming on human health due to temperature change. Food production changes and ultra-violet radiation effects and cataclysmic disaster effects. (author)

  13. Human Nature and its Implications for the Legal System | Obioha ...

    African Journals Online (AJOL)

    This paper examines the implications the various conceptions of human nature hold for the legal system. No doubt, there are various and conflicting theories of human nature such that the concept of human nature seems to have remained elusive and pervasive. Some conceive man as nothing but matter pure and simple; ...

  14. Introducing change in organization: implication for human resource ...

    African Journals Online (AJOL)

    Introducing change in organization: implication for human resource ... that one of the most obvious and urgent problems at management level in organizations is ... to change their attitude and behavior as rapidly as their organization requires.

  15. Implications of interaction between Humans and Structures

    DEFF Research Database (Denmark)

    Pedersen, Lars

    2015-01-01

    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 a...

  16. Human-structure Interaction and Implications

    DEFF Research Database (Denmark)

    Pedersen, Lars

    2016-01-01

    On civil engineering structures human occupancy is often modeled as a static load. Modeling humans as a static load is a simplification of matters, as will be demonstrated in the paper. The paper addresses the complexity of having both passive humans (sitting or standing) as well as active humans...

  17. Therapeutic implications of recombinant human erythropoietin in ...

    African Journals Online (AJOL)

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... quence of both, RHUEPO has achieved the highest annual sales ... analysis of the US Medicare database (Ma et al., 1999) ... blood transfusions and improves quality of life (Eschbach, ... Large doses of EPO results increase in blood pressure .... human erythropoietin was obtained from human genomic.

  18. Human rights: implications for patients and staff.

    Science.gov (United States)

    Dreezen, I; Nys, H

    2003-01-01

    Originating from wider declarations of fundamental human rights, individual human rights in the field of health care, also called patients' rights, have been elaborated, developed and implemented by most international organisations, including the European Union and the World Health Organisation. The Council of Europe is however, particularly prominent in its work in the field of human rights, having drawn up a number of vital international treaties, among them and most importantly the Convention on Human Rights and Biomedicine, which strengthens internationally the legal position of the patient and the research subject in setting a minimum level of protection in respect of individual human rights and health and is binding upon the member states that have ratified it. Nonetheless, it needs to be examined to see if the European Union would be a better alternative to regulate these patients' rights.

  19. 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

  20. Helminth Genomics: The Implications for Human Health

    Science.gov (United States)

    Brindley, Paul J.; Mitreva, Makedonka; Ghedin, Elodie; Lustigman, Sara

    2009-01-01

    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. PMID:19855829

  1. Knowledge management: implications for human service organizations.

    Science.gov (United States)

    Austin, Michael J; Claassen, Jennette; Vu, Catherine M; Mizrahi, Paola

    2008-01-01

    Knowledge management has recently taken a more prominent role in the management of organizations as worker knowledge and intellectual capital are recognized as critical to organizational success. This analysis explores the literature of knowledge management including the individual level of tacit and explicit knowledge, the networks and social interactions utilized by workers to create and share new knowledge, and the multiple organizational and managerial factors associated with effective knowledge management systems. Based on the role of organizational culture, structure, leadership, and reward systems, six strategies are identified to assist human service organizations with implementing new knowledge management systems.

  2. Aberrant septin 9 DNA methylation in colorectal cancer is restricted to a single CpG island

    International Nuclear Information System (INIS)

    Wasserkort, Reinhold; Kalmar, Alexandra; Valcz, Gabor; Spisak, Sandor; Krispin, Manuel; Toth, Kinga; Tulassay, Zsolt; Sledziewski, Andrew Z; Molnar, Bela

    2013-01-01

    The septin 9 gene (SEPT9) codes for a GTP-binding protein associated with filamentous structures and cytoskeleton formation. SEPT9 plays a role in multiple cancers as either an oncogene or a tumor suppressor gene. Regulation of SEPT9 expression is complex and not well understood; however, hypermethylation of the gene was recently introduced as a biomarker for early detection of colorectal cancer (CRC) and has been linked to cancer of the breast and of the head and neck. Because the DNA methylation landscape of different regions of SEPT9 is poorly understood in cancer, we analyzed the methylation patterns of this gene in distinct cell populations from normal and diseased colon mucosa. Laser capture microdissection was performed to obtain homogeneous populations of epithelial and stromal cells from normal, adenomatous, and tumorous colon mucosa. Microdissected samples were analyzed using direct bisulfite sequencing to determine the DNA methylation status of eight regions within and near the SEPT9 gene. Septin-9 protein expression was assessed using immunohistochemistry (IHC). Regions analyzed in SEPT9 were unmethylated in normal tissue except for a methylation boundary detected downstream of the largest CpG island. In adenoma and tumor tissues, epithelial cells displayed markedly increased DNA methylation levels (>80%, p <0.0001) in only one of the CpG islands investigated. SEPT9 methylation in stromal cells increased in adenomatous and tumor tissues (≤50%, p <0.0001); however, methylation did not increase in stromal cells of normal tissue close to the tumor. IHC data indicated a significant decrease (p <0.01) in Septin-9 protein levels in epithelial cells derived from adenoma and tumor tissues; Septin-9 protein levels in stromal cells were low in all tissues. Hypermethylation of SEPT9 in adenoma and CRC specimens is confined to one of several CpG islands of this gene. Tumor-associated aberrant methylation originates in epithelial cells; stromal cells appear to

  3. Blastomyces dermatitidis septins CDC3, CDC10, and CDC12 impact the morphology of yeast and hyphae, but are not required for the phase transition.

    Science.gov (United States)

    Marty, Amber J; Gauthier, Gregory M

    2013-01-01

    Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in response to temperature. The contribution of structural proteins such as septins to this phase transition in these fungi remains poorly understood. Septins are GTPases that serve as a scaffold for proteins involved with cytokinesis, cell polarity, and cell morphology. In this study, we use a GFP sentinel RNA interference system to investigate the impact of CDC3, CDC10, CDC12, and ASPE on the morphology and phase transition of B. dermatitidis. Targeting CDC3, CDC10, and CDC12 by RNA interference resulted in yeast with aberrant morphology at 37°C with defects in cytokinesis. Downshifting the temperature to 22°C promoted the conversion to the mold phase, but did not abrogate the morphologic defects. CDC3, CDC10, and CDC12 knockdown strains grew as mold with curved, thickened hyphae. Knocking down ASPE transcript did not alter morphology of yeast at 37°C or mold at 22°C. Following an increase in temperature from 22°C to 37°C, all septin knockdown strains were able to revert to yeast. In conclusion, CDC3, CDC10, and CDC12 septin- encoding genes are required for proper morphology of yeast and hyphae, but are dispensable for the phase transition.

  4. 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.

  5. Medical humanities and their discontents: definitions, critiques, and implications.

    Science.gov (United States)

    Shapiro, Johanna; Coulehan, Jack; Wear, Delese; Montello, Martha

    2009-02-01

    The humanities offer great potential for enhancing professional and humanistic development in medical education. Yet, although many students report benefit from exposure to the humanities in their medical education, they also offer consistent complaints and skepticism. The authors offer a pedagogical definition of the medical humanities, linking it to medicine as a practice profession. They then explore three student critiques of medical humanities curricula: (1) the content critique, examining issues of perceived relevance and intellectual bait-and-switch, (2) the teaching critique, which examines instructor trustworthiness and perceived personal intrusiveness, and (3) the structural/placement critique, or how and when medical humanities appear in the curriculum. Next, ways are suggested to tailor medical humanities to better acknowledge and reframe the needs of medical students. These include ongoing cross-disciplinary reflective practices in which intellectual tools of the humanities are incorporated into educational activities to help students examine and, at times, contest the process, values, and goals of medical practice. This systematic, pervasive reflection will organically lead to meaningful contributions from the medical humanities in three specific areas of great interest to medical educators: professionalism, "narrativity," and educational competencies. Regarding pedagogy, the implications of this approach are an integrated required curriculum and innovative concepts such as "applied humanities scholars." In turn, systematic integration of humanities perspectives and ways of thinking into clinical training will usefully expand the range of metaphors and narratives available to reflect on medical practice and offer possibilities for deepening and strengthening professional education.

  6. 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…

  7. International Security Presence in Kosovo and its Human Rights Implications

    Directory of Open Access Journals (Sweden)

    Istrefi Remzije

    2017-11-01

    Full Text Available In this article I will examine the powers and activities of NATO-led Kosovo forces (KFOR and their impact on human rights protection in Kosovo. Through this examination, I seek to answer the following questions: which KFOR actions affected the human rights of Kosovars? Does KFOR carry out responsibilities and abide by the obligations normally imposed upon nation-states? And is there a solution available when the alleged violator is KFOR? KFOR is responsible for carrying out military tasks and for ‘shouldering’ UNMIK and local security forces in some civilian peace-building tasks. In the course of the exercise of its mandate, there were alleged complaints of human rights violations by KFOR. The legal implications of these alleged complaints against KFOR (inactions will also be discussed.

  8. The development of human visual cortex and clinical implications

    Directory of Open Access Journals (Sweden)

    Siu CR

    2018-04-01

    Full Text Available Caitlin R Siu,1 Kathryn M Murphy1,2 1McMaster Integrative Neuroscience Discovery and Study (MiNDS Program, McMaster University, Hamilton, ON, Canada; 2Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada Abstract: The primary visual cortex (V1 is the first cortical area that processes visual information. Normal development of V1 depends on binocular vision during the critical period, and age-related losses of vision are linked with neurobiological changes in V1. Animal studies have provided important details about the neurobiological mechanisms in V1 that support normal vision or are changed by visual diseases. There is very little information, however, about those neurobiological mechanisms in human V1. That lack of information has hampered the translation of biologically inspired treatments from preclinical models to effective clinical treatments. We have studied human V1 to characterize the expression of neurobiological mechanisms that regulate visual perception and neuroplasticity. We have identified five stages of development for human V1 that start in infancy and continue across the life span. Here, we describe these stages, compare them with visual and anatomical milestones, and discuss implications for translating treatments for visual disorders that depend on neuroplasticity of V1 function. Keywords: development, human visual cortex, amblyopia, synaptic plasticity, glutamatergic, GABAergic, receptors

  9. Strategic Implications of Human Exploration of Near-Earth Asteroids

    Science.gov (United States)

    Drake, Bret G.

    2011-01-01

    The current United States Space Policy [1] as articulated by the White House and later confirmed by the Congress [2] calls for [t]he extension of the human presence from low-Earth orbit to other regions of space beyond low-Earth orbit will enable missions to the surface of the Moon and missions to deep space destinations such as near-Earth asteroids and Mars. Human exploration of the Moon and Mars has been the focus of numerous exhaustive studies and planning, but missions to Near-Earth Asteroids (NEAs) has, by comparison, garnered relatively little attention in terms of mission and systems planning. This paper examines the strategic implications of human exploration of NEAs and how they can fit into the overall exploration strategy. This paper specifically addresses how accessible NEAs are in terms of mission duration, technologies required, and overall architecture construct. Example mission architectures utilizing different propulsion technologies such as chemical, nuclear thermal, and solar electric propulsion were formulated to determine resulting figures of merit including number of NEAs accessible, time of flight, mission mass, number of departure windows, and length of the launch windows. These data, in conjunction with what we currently know about these potential exploration targets (or need to know in the future), provide key insights necessary for future mission and strategic planning.

  10. International financial institutions and human rights: implications for public health.

    Science.gov (United States)

    Stubbs, Thomas; Kentikelenis, Alexander

    2017-01-01

    Serving as lender of last resort to countries experiencing unsustainable levels of public debt, international financial institutions have attracted intense controversy over the past decades, exemplified most recently by the popular discontent expressed in Eurozone countries following several rounds of austerity measures. In exchange for access to financial assistance, borrowing countries must settle on a list of often painful policy reforms that are aimed at balancing the budget. This practice has afforded international financial institutions substantial policy influence on governments throughout the world and in a wide array of policy areas of direct bearing on human rights. This article reviews the consequences of policy reforms mandated by international financial institutions on the enjoyment of human rights, focusing on the International Monetary Fund and World Bank. It finds that these reforms undermine the enjoyment of health rights, labour rights, and civil and political rights, all of which have deleterious implications for public health. The evidence suggests that for human rights commitments to be met, a fundamental reorientation of international financial institutions' activities will be necessary.

  11. 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.

  12. Social media: implications for everyday life, politics and human agency

    Directory of Open Access Journals (Sweden)

    André Jansson

    2013-11-01

    Full Text Available With the current saturation of digital devices in contemporary society, the boundaries between humans and machines have become increasingly blurred. This digitalization of everyday life both obscures and reminds us of the fact that identity, agency and power cannot be attributed to the individual or the machine alone: rather, they are the outcome of interactions and negotiations within a network of actors. Social media, such as Facebook, blogs, Twitter and YouTube, show clearly that the ‘meaning’ or ‘effect’ of digital technologies is formed through the practices in which they are used and the social relations and institutions that develop around them. This article presents views expressed during a panel discussion on the implications of social media for everyday life, politics and human agency at the Aboagora Symposium, held on 14th August 2013. The panel was organized as a dialogue between the participants and the discussion was structured around three questions, presented below. The participants in the panel were; Professor André Jansson (Karlstad University, Professor Susanna Paasonen (University of Turku and adjunct Professor Johanna Sumiala (University of Helsinki. The panel was chaired by Professor Mia Lövheim (Uppsala University.

  13. 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.

  14. The human genome as public: Justifications and implications.

    Science.gov (United States)

    Bayefsky, Michelle J

    2017-03-01

    Since the human genome was decoded, great emphasis has been placed on the unique, personal nature of the genome, along with the benefits that personalized medicine can bring to individuals and the importance of safeguarding genetic privacy. As a result, an equally important aspect of the human genome - its common nature - has been underappreciated and underrepresented in the ethics literature and policy dialogue surrounding genetics and genomics. This article will argue that, just as the personal nature of the genome has been used to reinforce individual rights and justify important privacy protections, so too the common nature of the genome can be employed to support protections of the genome at a population level and policies designed to promote the public's wellbeing. In order for public health officials to have the authority to develop genetics policies for the sake of the public good, the genome must have not only a common, but also a public, dimension. This article contends that DNA carries a public dimension through the use of two conceptual frameworks: the common heritage (CH) framework and the common resource (CR) framework. Both frameworks establish a public interest in the human genome, but the CH framework can be used to justify policies aimed at preserving and protecting the genome, while the CR framework can be employed to justify policies for utilizing the genome for the public benefit. A variety of possible policy implications are discussed, with special attention paid to the use of large-scale genomics databases for public health research. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  15. Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans

    Science.gov (United States)

    Varki, Ajit

    2004-06-01

    At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.

  16. Implications of human tissue studies for radiation protection

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1988-01-01

    Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238 Pu and 241 Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices

  17. Implications for human health of global atmospheric changes

    International Nuclear Information System (INIS)

    Guidotti, T.L.; Last, J.

    1991-01-01

    The possible impacts of the greenhouse effect, ozone depletion and ultraviolet irradiation, acid precipitation, and resulting demographic changes are reviewed, along with the implications of global ecological changes on society and sustainable development. Some manifestations of global warming caused by the greenhouse effect could include more frequently extreme weather conditions, rises in sea level, disruption of ocean currents, and changes in composition and distribution of vegetation. Consequences of these manifestations on human health include an increase in the frequency of droughts and heat waves, migration of disease carrying vectors to other areas, submergence of coastal areas and disruption of water supplies, destruction of tropical species potentially useful for medicinal purposes, and impaired production of crops leading to food shortages. Consequences of stratospheric ozone depletion due to chlorofluorocarbon pollution are thought to be a direct result of increased exposure to ultraviolet light; these consequences include higher risks of non-melanoma skin cancer. The effects of acid precipitation are thought to be primarily ecological and indirect. 61 refs,

  18. Implications of human tissue studies for radiation protection.

    Science.gov (United States)

    Kathren, R L

    1988-08-01

    Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238Pu and 241Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices.

  19. 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.

  20. Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health.

    Science.gov (United States)

    Xiang, Ping; Liu, Rong-Yan; Li, Chao; Gao, Peng; Cui, Xin-Yi; Ma, Lena Q

    2017-11-01

    Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC 50 at 202 μg/mL. A concentration-dependent apoptotic sign was observed in HCECs after exposing to ≥2 μg/mL TDCPP. Endoplasmic reticulum stress induction was evidenced by up-regulation of its biomarker genes (ATF-4, CHOP, BiP, and XBP1). Furthermore, alternation of Bcl-2/Bax expression, mitochondrial membrane potential loss, cellular ATP content decrease, and caspase-3 and -9 activity increase were observed after exposing to 2 or 20 μg/mL TDCPP. Taken together, the data implicated the involvement of endoplasmic reticulum stress in TDCPP-induced HCEC apoptosis, probably mediated by mitochondrial apoptotic pathway. Our findings showed TDCPP exposure induced toxicity to human cornea. Due to TDCPP's presence at high levels in indoor dust, further study is warranted to evaluate its health risk on human corneas. Published by Elsevier Ltd.

  1. 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

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

    International Nuclear Information System (INIS)

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-01

    Research highlights: → Primary keratinocytes express the steroid enzymes required for cortisol synthesis. → Normal primary human keratinocytes can synthesise cortisol. → Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. → StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3βHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7- 3 H]-pregnenolone through each steroid intermediate to [7- 3 H]-cortisol in cultured PHK. Trilostane (a 3βHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra

  3. Genomics and the human genome project: implications for psychiatry

    OpenAIRE

    Kelsoe, J R

    2004-01-01

    In the past decade the Human Genome Project has made extraordinary strides in understanding of fundamental human genetics. The complete human genetic sequence has been determined, and the chromosomal location of almost all human genes identified. Presently, a large international consortium, the HapMap Project, is working to identify a large portion of genetic variation in different human populations and the structure and relationship of these variants to each other. The Human Genome Project h...

  4. Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yuting, E-mail: wuyuting1302@sina.com; Bu, Fangtian; Yu, Haixia; Li, Wanxia; Huang, Cheng; Meng, Xiaoming; Zhang, Lei; Ma, Taotao; Li, Jun, E-mail: lj@ahmu.edu.cn

    2017-01-15

    Liver fibrosis, resulting from chronic and persistent injury to the liver, is a worldwide health problem. Advanced liver fibrosis results in cirrhosis, liver failure and even hepatocellular cancer (HCC), often eventually requiring liver transplantation, poses a huge health burden on the global community. However, the specific pathogenesis of liver fibrosis remains not fully understood. Numerous basic and clinical studies have provided evidence that epigenetic modifications, especially DNA methylation, might contribute to the activation of hepatic stellate cells (HSCs), the pivotal cell type responsible for the fibrous scar in liver. Here, reduced representation bisulfite sequencing (RRBS) and bisulfite pyrosequencing PCR (BSP) analysis identified hypermethylation status of Septin9 (Sept9) gene in liver fibrogenesis. Sept9 protein was dramatically decreased in livers of CCl4-treated mice and immortalized HSC-T6 cells exposed to TGF-β1. Nevertheless, the suppression of Sept9 could be blocked by DNMT3a-siRNA and DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-azadC). Overexpressed Sept9 attenuated TGF-β1-induced expression of myofibroblast markers α-SMA and Col1a1, accompanied by up-regulation of cell apoptosis-related proteins. Conversely, RNAi-mediated silencing of Sept9 enhanced accumulation of extracellular matrix. These observations suggested that Sept9 contributed to alleviate liver fibrosis might partially through promoting activated HSCs apoptosis and this anti-fibrogenesis effect might be blocked by DNMT-3a mediated methylation of Sept9. Therefore, pharmacological agents that inhibit Sept9 methylation and increase its expression could be considered as valuable treatments for liver fibrosis. - Highlights: • This is the first report of Sept9 methylation and function in liver fibrosis. • Ectopic expression of Sept9 could block the liver fibrogenesis. • DNMT3a might be responsible for the suppression of Sept9 in liver fibrosis.

  5. Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis

    International Nuclear Information System (INIS)

    Wu, Yuting; Bu, Fangtian; Yu, Haixia; Li, Wanxia; Huang, Cheng; Meng, Xiaoming; Zhang, Lei; Ma, Taotao; Li, Jun

    2017-01-01

    Liver fibrosis, resulting from chronic and persistent injury to the liver, is a worldwide health problem. Advanced liver fibrosis results in cirrhosis, liver failure and even hepatocellular cancer (HCC), often eventually requiring liver transplantation, poses a huge health burden on the global community. However, the specific pathogenesis of liver fibrosis remains not fully understood. Numerous basic and clinical studies have provided evidence that epigenetic modifications, especially DNA methylation, might contribute to the activation of hepatic stellate cells (HSCs), the pivotal cell type responsible for the fibrous scar in liver. Here, reduced representation bisulfite sequencing (RRBS) and bisulfite pyrosequencing PCR (BSP) analysis identified hypermethylation status of Septin9 (Sept9) gene in liver fibrogenesis. Sept9 protein was dramatically decreased in livers of CCl4-treated mice and immortalized HSC-T6 cells exposed to TGF-β1. Nevertheless, the suppression of Sept9 could be blocked by DNMT3a-siRNA and DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-azadC). Overexpressed Sept9 attenuated TGF-β1-induced expression of myofibroblast markers α-SMA and Col1a1, accompanied by up-regulation of cell apoptosis-related proteins. Conversely, RNAi-mediated silencing of Sept9 enhanced accumulation of extracellular matrix. These observations suggested that Sept9 contributed to alleviate liver fibrosis might partially through promoting activated HSCs apoptosis and this anti-fibrogenesis effect might be blocked by DNMT-3a mediated methylation of Sept9. Therefore, pharmacological agents that inhibit Sept9 methylation and increase its expression could be considered as valuable treatments for liver fibrosis. - Highlights: • This is the first report of Sept9 methylation and function in liver fibrosis. • Ectopic expression of Sept9 could block the liver fibrogenesis. • DNMT3a might be responsible for the suppression of Sept9 in liver fibrosis.

  6. 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

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

    Science.gov (United States)

    O'Mathúna, Dónal P

    2006-03-14

    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. 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. 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 era proved destructive to many humans. Their widespread

  8. 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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  9. Human right education and the Nigerian child: implications for ...

    African Journals Online (AJOL)

    This paper examines the concept of human right to education as listed in Article 26 of the United Nations Declaration of Human Rights of December 1948. Human right is viewed as natural or moral law which has the force of conscience. The declaration is directed at the right to formal Western education in Nigeria, rather ...

  10. Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elwafa Abdallah, Mohamed, E-mail: mae_abdallah@yahoo.co.uk [Division of Environmental Health and Risk Management, School of Geography, Earth, and Environmental Sciences, University of Birmingham, Birmingham B15 2TT (United Kingdom); Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut (Egypt); Pawar, Gopal; Harrad, Stuart [Division of Environmental Health and Risk Management, School of Geography, Earth, and Environmental Sciences, University of Birmingham, Birmingham B15 2TT (United Kingdom)

    2016-01-15

    Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm{sup 2}, finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPP and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K{sub p}, cm/h) showed a significant negative correlation with log K{sub ow} for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K{sub ow} of PFRs. • Skin washing reduced the overall dermal

  11. Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

    International Nuclear Information System (INIS)

    Abou-Elwafa Abdallah, Mohamed; Pawar, Gopal; Harrad, Stuart

    2016-01-01

    Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm 2 , finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPP and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K p , cm/h) showed a significant negative correlation with log K ow for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K ow of PFRs. • Skin washing reduced the overall dermal absorption of target PFRs

  12. 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.

  13. The human gut microbiota and virome: Potential therapeutic implications.

    Science.gov (United States)

    Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio

    2015-12-01

    Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  14. Xenophobia: A crime against humanity and its attendant implications ...

    African Journals Online (AJOL)

    ... and in conclusion, it puts forward amongst other recommendations that the provisions of Article 7 of the Rome Statute of the International Criminal Court should be enlarged to provide for xenophobia as a crime against humanity. Keywords: Xenophobia, Duty of State, Crime against Humanity, Migrants, Rights, Aliens ...

  15. 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…

  16. The Stool DNA Test is More Accurate than the Plasma Septin 9 Test in Detecting Colorectal Neoplasia

    Science.gov (United States)

    Ahlquist, David A.; Taylor, William R.; Mahoney, Douglas W.; Zou, Hongzhi; Domanico, Michael; Thibodeau, Stephen N.; Boardman, Lisa A.; Berger, Barry M.; Lidgard, Graham P.

    2014-01-01

    Background & Aims Several noninvasive tests have been developed for colorectal cancer (CRC) screening. We compared the sensitivities of a multi-marker test for stool DNA (sDNA) and a plasma test for methylated Septin 9 (SEPT9) in identifying patients with large adenomas or CRC. Methods We analyzed paired stool and plasma samples from 30 patients with CRC and 22 with large adenomas from Mayo Clinic archives. Stool (n=46) and plasma (n=49) samples from age- and sex-matched patients with normal colonoscopy results were used as controls. The sDNA test is an assay for methylated BMP3, NDRG4, vimentin, and TFPI2; mutant KRAS; the β-actin gene, and quantity of hemoglobin (by the porphyrin method). It was performed blindly at Exact Sciences (Madison WI); the test for SEPT9 was performed at ARUP Laboratories (Salt Lake City UT). Results were considered positive based on the manufacturer's specificity cutoff values of 90% and 89%, respectively. Results The sDNA test detected adenomas (median 2 cm, range 1–5 cm) with 82% sensitivity (95% confidence interval [CI], 60%–95%); SEPT9 had 14% sensitivity (95% CI, 3%–35%; P=.0001). The sDNA test identified patients with CRC with 87% sensitivity (95% CI, 69%–96%); SEPT9 had 60% sensitivity (95% CI, 41%–77%; P=.046). The sDNA test identified patients with stage I–III CRC with 91% sensitivity (95% CI, 71%–99%); SEPT9 had 50% sensitivity (95% CI, 28%–72%; P=.013); for stage IV CRC, sensitivity values were 75% (95% CI, 35%–97%) and 88% (95% CI, 47%–100%), respectively (P=.56). False-positive rates were 7% for the sDNA test and 27% for SEPT9. Conclusions Based on analyses of paired samples, the sDNA test detects non-metastatic CRC and large adenomas with significantly greater levels of sensitivity than the SEPT9 test. These findings might be used to modify approaches for CRC prevention and early detection. PMID:22019796

  17. Polar bear attacks on humans: Implications of a changing climate

    Science.gov (United States)

    Wilder, James; Vongraven, Dag; Atwood, Todd C.; Hansen, Bob; Jessen, Amalie; Kochnev, Anatoly A.; York, Geoff; Vallender, Rachel; Hedman, Daryll; Gibbons, Melissa

    2017-01-01

    Understanding causes of polar bear (Ursus maritimus) attacks on humans is critical to ensuring both human safety and polar bear conservation. Although considerable attention has been focused on understanding black (U. americanus) and grizzly (U. arctos) bear conflicts with humans, there have been few attempts to systematically collect, analyze, and interpret available information on human-polar bear conflicts across their range. To help fill this knowledge gap, a database was developed (Polar Bear-Human Information Management System [PBHIMS]) to facilitate the range-wide collection and analysis of human-polar bear conflict data. We populated the PBHIMS with data collected throughout the polar bear range, analyzed polar bear attacks on people, and found that reported attacks have been extremely rare. From 1870–2014, we documented 73 attacks by wild polar bears, distributed among the 5 polar bear Range States (Canada, Greenland, Norway, Russia, and United States), which resulted in 20 human fatalities and 63 human injuries. We found that nutritionally stressed adult male polar bears were the most likely to pose threats to human safety. Attacks by adult females were rare, and most were attributed to defense of cubs. We judged that bears acted as a predator in most attacks, and that nearly all attacks involved ≤2 people. Increased concern for both human and bear safety is warranted in light of predictions of increased numbers of nutritionally stressed bears spending longer amounts of time on land near people because of the loss of their sea ice habitat. Improved conflict investigation is needed to collect accurate and relevant data and communicate accurate bear safety messages and mitigation strategies to the public. With better information, people can take proactive measures in polar bear habitat to ensure their safety and prevent conflicts with polar bears. This work represents an important first step towards improving our understanding of factors influencing

  18. Ethical implications of implantable radiofrequency identification (RFID) tags in humans.

    Science.gov (United States)

    Foster, Kenneth R; Jaeger, Jan

    2008-08-01

    This article reviews the use of implantable radiofrequency identification (RFID) tags in humans, focusing on the VeriChip (VeriChip Corporation, Delray Beach, FL) and the associated VeriMed patient identification system. In addition, various nonmedical applications for implanted RFID tags in humans have been proposed. The technology offers important health and nonhealth benefits, but raises ethical concerns, including privacy and the potential for coercive implantation of RFID tags in individuals. A national discussion is needed to identify the limits of acceptable use of implantable RFID tags in humans before their use becomes widespread and it becomes too late to prevent misuse of this useful but ethically problematic technology.

  19. Nanotechnology in Medicine: Implications of converging technologies on humanity

    OpenAIRE

    Debra Bennett-Woods

    2006-01-01

    Nanotechnology holds great potential as an enabler of a wide range of biotechnologies that will change the face of medicine and may eventually alter the very definition of human health. Deb Bennett-Woods argues that these changes will also pose unprecedented challenges regarding access to health-related technologies, the meaning of consent, and the nature of human identity. Development (2006) 49, 54–59. doi:10.1057/palgrave.development.1100297

  20. International Security Presence in Kosovo and its Human Rights Implications

    OpenAIRE

    Istrefi, Remzije

    2017-01-01

    In this article I will examine the powers and activities of NATO-led Kosovo forces (KFOR) and their impact on human rights protection in Kosovo. Through this examination, I seek to answer the following questions: which KFOR actions affected the human rights of Kosovars? Does KFOR carry out responsibilities and abide by the obligations normally imposed upon nation-states? And is there a solution available when the alleged violator is KFOR? KFOR is responsible for carrying out military tasks an...

  1. 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.

  2. Evolution of Human Body Height and Its Implications in Ergonomics

    Directory of Open Access Journals (Sweden)

    İzzet DUYAR

    2009-06-01

    Full Text Available Body height is an crucial variable in the design and production of all physical spaces, primarily in the manifacturing of clothes and means of transportation. Having such an ergonomic significance, the height of the human being has constantly changed during the course of history. There exist strong data suggesting that this change is still continue. To find out stages of evolution of human height throughout the ages up to the present will help us to illuminate the human-environment relations, and to predict the possible changes that the human height might be subjected to in the future. In view of these reasons, the changes that has occured in human height from the period at which hominids appeared until humans’ transition into settled life have been closely examined. The study was carried out on the basis of the data obtained from the earlier studies in literature. These data, when considered as a whole, reveal that the human height did not continuously increase in a linear fashion in its evolutionary path but recorded some increases and decreases at different stages. The difference between males and females (sexual dimorphism has not shown a steady decrease either; instead, it has exhibited an oscillating pattern. The modern humans as a species is not unique in terms of their height; as a matter of fact, two million years ago hominids had existed at approximately the same height as the Homo sapiens. Although the average height had shown some decrease in Homo erectus, its distribution pattern was not much different than the one observed in the modern human societies. In the findings dated to the early stages of the Upper Paleolithic Age, height showed a tendency to increase again

  3. Soy and Gut Microbiota: Interaction and Implication for Human Health.

    Science.gov (United States)

    Huang, Haiqiu; Krishnan, Hari B; Pham, Quynhchi; Yu, Liangli Lucy; Wang, Thomas T Y

    2016-11-23

    Soy (Glycine max) is a major commodity in the United States, and soy foods are gaining popularity due to their reported health-promoting effects. In the past two decades, soy and soy bioactive components have been studied for their health-promoting/disease-preventing activities and potential mechanisms of action. Recent studies have identified gut microbiota as an important component in the human body ecosystem and possibly a critical modulator of human health. Soy foods' interaction with the gut microbiota may critically influence many aspects of human development, physiology, immunity, and nutrition at different stages of life. This review summarizes current knowledge on the effects of soy foods and soy components on gut microbiota population and composition. It was found, although results vary in different studies, in general, both animal and human studies have shown that consumption of soy foods can increase the levels of bifidobacteria and lactobacilli and alter the ratio between Firmicutes and Bacteroidetes. These changes in microbiota are consistent with reported reductions in pathogenic bacteria populations in the gut, thereby lowering the risk of diseases and leading to beneficial effects on human health.

  4. 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.

  5. Developing Entrepreneurial Resilience: Implications for Human Resource Development

    Science.gov (United States)

    Lee, Jin; Wang, Jia

    2017-01-01

    Purpose: Leadership development has attracted much research attention within the human resource development (HRD) community. However, little scholarly effort has been made to study a special group of leaders--entrepreneurs. This paper aims to fill in this knowledge gap by taking a close look at entrepreneurial resilience, a key ability of…

  6. 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.

  7. Gender inequality and domestic violence: implications for human ...

    African Journals Online (AJOL)

    Domestic violence and human immunodeficiency virus (HIV) infection are problems of great public health worldwide, especially sub-Saharan Africa and much of the developing countries. This is due to their far reaching social, economic and public health consequences. The two problems have gender inequality and gender ...

  8. Implication of human factors in terms of safety

    International Nuclear Information System (INIS)

    Furuta, Kazuo

    2001-01-01

    A critical accident of JCO occurred on September 30, 1999 gave a large impact not only to common society but also to nuclear energy field. This accident occurred by direct reason perfectly out of forecasting of the participants of nuclear energy, where a company made up a guideline violating from business allowance and safety rule and workmen also operated under a procedure out of the guideline. After the accident, a number of countermeasures on equipments, rules, and regulations were carried out, but discussion on software such as their operating methods, concrete regulation on business and authority of operators, and training of specialists seems to be much late. Safety is a problem on a complex system, containing not only hardware but also software such as human, organization, society, and so on. Then, here was discussed on a problem directly faced by conventional safety, engineering centering at hardware through thinking of a problem on human factors. (G.K.)

  9. Human health implications of organic food and organic agriculture

    DEFF Research Database (Denmark)

    Mie, Axel; Andersen, Helle Raun; Gunnarsson, Stefan

    2017-01-01

    . Organic food consumption may reduce the risk of allergic disease and of overweight and obesity, but the evidence is not conclusive due to likely residual confounding, as consumers of organic food tend to have healthier lifestyles overall. However, animal experiments suggest that identically composed feed...... benefits associated with organic food production, and application of such production methods is likely to be beneficial within conventional agriculture, e.g., in integrated pest management.......This review summarises existing evidence on the impact of organic food on human health. It compares organic vs. conventional food production with respect to parameters important to human health and discusses the potential impact of organic management practices with an emphasis on EU conditions...

  10. Nanotechnology: Societal Implications - I. Maximising Benefits for Humanity

    Science.gov (United States)

    Roco, Mihail C.; Bainbridge, William S.

    Advances in nanoscience and nanotechnology promise to have major impacts on human health, wealth, and peace in the coming decades. Among the expected breakthroughs are `designer' materials created from directed assembly of atoms and molecules, and the emergence of entirely new phenomena in chemistry and physics. This book includes a collection of essays by leading scientists, engineers, and social scientists reviewing the possible uses of these impending developments in various applications, and the corresponding issues that they raise.

  11. Architecture of the human renal inner medulla and functional implications.

    Science.gov (United States)

    Wei, Guojun; Rosen, Seymour; Dantzler, William H; Pannabecker, Thomas L

    2015-10-01

    The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. Copyright © 2015 the American Physiological Society.

  12. The human influence on seabird nesting success: Conservation implications

    Science.gov (United States)

    Anderson, D.W.; Keith, J.O.

    1980-01-01

    Based on studies of brown pelicans Pelecanus occidentalis californicus and Heermann's gulls Larus heermanni, disturbances by recreationists, educational groups, local fishermen and scientists alike can be seriously disruptive and damaging to breeding seabirds in the Gulf of California and off the west coast of Baja California. Similar instances have been identified throughout the world?the problem is not difficult to document, but it is difficult to eliminate. The increasing human-seabird contacts on islands in the Gulf of California and along the west coast of Baja California raise serious questions and immediate concern about the continued preservation of nesting colonies of marine birds in those areas. Conservation measures must consider the extreme sensitivity of many seabirds to the inter- and intraspecific behavioural imbalances created by human disturbances. In some cases, total exclusion of humans may be required; in others, limited access might be possible under closely managed conditions at certain times of the year. A symbiotic relationship between seabird conservation, legitimate research and tourism should be the desired goal.

  13. 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.

  14. 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

  15. Enhanced/Synthetic Vision Systems - Human factors research and implications for future systems

    Science.gov (United States)

    Foyle, David C.; Ahumada, Albert J.; Larimer, James; Sweet, Barbara T.

    1992-01-01

    This paper reviews recent human factors research studies conducted in the Aerospace Human Factors Research Division at NASA Ames Research Center related to the development and usage of Enhanced or Synthetic Vision Systems. Research discussed includes studies of field of view (FOV), representational differences of infrared (IR) imagery, head-up display (HUD) symbology, HUD advanced concept designs, sensor fusion, and sensor/database fusion and evaluation. Implications for the design and usage of Enhanced or Synthetic Vision Systems are discussed.

  16. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  18. Implications of human trafficking in Asia: a scoping review of aftercare initiatives centered on economic development.

    Science.gov (United States)

    Camp, Meghan A; Barner, John R; Okech, David

    2018-01-01

    The trafficking of persons is one of the most egregious violations of human rights in modern society. Given the disproportionate effects across demographic categories of age and gender, as well as concentrated impacts within the developing world, there is a strong need for research and literature on program effectiveness and appropriate aftercare efforts for those persons whose lives and livelihoods have been impacted by trafficking. The purpose of this article is to provide a scoping review of what is known about effectively helping survivors of human trafficking experiencing lack of economic opportunity and the implications for practice and future research regarding the absence of literature. From over 14,000 initial search results, this article focuses on those initiatives (N = 16) that support economic development of the individual or family after being trafficked. Implications arising from the review for trafficking policy, areas for further research, and implications for practitioners are highlighted and discussed.

  19. 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)

  20. Characterisation of recombinant human fatty aldehyde dehydrogenase: implications for Sjögren-Larsson syndrome

    NARCIS (Netherlands)

    Lloyd, Matthew D.; Boardman, Kieren D. E.; Smith, Andrew; van den Brink, Daan M.; Wanders, Ronald J. A.; Threadgill, Michael D.

    2007-01-01

    Fatty aldehyde dehydrogenase (FALDH) is an NAD+-dependent oxidoreductase involved in the metabolism of fatty alcohols. Enzyme activity has been implicated in the pathology of diabetes and cancer. Mutations in the human gene inactivate the enzyme and cause accumulation of fatty alcohols in

  1. 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

    leading to the disruption of cascade of events important in the regulation and control of cellular processes. Covalent binding of microcystins with phosphatases is thought to be responsible for the cytotoxic and genotoxic effects of microcystins. In addition, microcystins can trigger oxidative stress......Microcystins are cyclic heptapeptide toxins produced by a number of genera of cyanobacteria. They are ubiquitous in bodies of water worldwide and pose significant hazard to human, plant, and animal health. Microcystins are primarily hepatotoxins known to inhibit serine-threonine phosphatases...... harmful bloom events. Combination of conventional and advanced oxidation technologies can potentially remove 100% of microcystins in water even in turbid conditions. This review covers selected treatment technologies to degrade microcystins in water....

  2. Berry Phenolic Antioxidants – Implications for Human Health?

    Science.gov (United States)

    Olas, Beata

    2018-01-01

    Antioxidants present in the diet may have a significant effect on the prophylaxis and progression of various diseases associated with oxidative stress. Berries contain a range of chemical compounds with antioxidant properties, including phenolic compounds. The aim of this review article is to provide an overview of the current knowledge of such phenolic antioxidants, and to discuss whether these compounds may always be natural gifts for human health, based on both in vitro and in vivo studies. It describes the antioxidant properties of fresh berries (including aronia berries, grapes, blueberries, sea buckthorn berries, strawberries and other berries) and their various products, especially juices and wines. Some papers report that these phenolic compounds may sometimes behave like prooxidants, and sometimes demonstrate both antioxidant and prooxidant activity, while others note they do not behave the same way in vitro and in vivo. However, no unwanted or toxic effects (i.e., chemical, hematological or urinary effect) have been associated with the consumption of berries or berry juices or other extracts, especially aronia berries and aronia products in vivo, and in vitro, which may suggest that the phenolic antioxidants found in berries are natural gifts for human health. However, the phenolic compound content of berries and berry products is not always well described, and further studies are required to determine the therapeutic doses of different berry products for use in future clinical studies. Moreover, further experiments are needed to understand the beneficial effects reported so far from the mechanistic point of view. Therefore, greater attention should be paid to the development of well-controlled and high-quality clinical studies in this area. PMID:29662448

  3. Proline and hydroxyproline metabolism: implications for animal and human nutrition

    Science.gov (United States)

    Bazer, Fuller W.; Burghardt, Robert C.; Johnson, Gregory A.; Kim, Sung Woo; Knabe, Darrell A.; Li, Peng; Li, Xilong; McKnight, Jason R.; Satterfield, M. Carey; Spencer, Thomas E.

    2013-01-01

    Proline plays important roles in protein synthesis and structure, metabolism (particularly the synthesis of arginine, polyamines, and glutamate via pyrroline-5-carboxylate), and nutrition, as well as wound healing, antioxidative reactions, and immune responses. On a pergram basis, proline plus hydroxyproline are most abundant in collagen and milk proteins, and requirements of proline for whole-body protein synthesis are the greatest among all amino acids. Therefore, physiological needs for proline are particularly high during the life cycle. While most mammals (including humans and pigs) can synthesize proline from arginine and glutamine/glutamate, rates of endogenous synthesis are inadequate for neonates, birds, and fish. Thus, work with young pigs (a widely used animal model for studying infant nutrition) has shown that supplementing 0.0, 0.35, 0.7, 1.05, 1.4, and 2.1% proline to a proline-free chemically defined diet containing 0.48% arginine and 2% glutamate dose dependently improved daily growth rate and feed efficiency while reducing concentrations of urea in plasma. Additionally, maximal growth performance of chickens depended on at least 0.8% proline in the diet. Likewise, dietary supplementation with 0.07, 0.14, and 0.28% hydroxyproline (a metabolite of proline) to a plant protein-based diet enhanced weight gains of salmon. Based on its regulatory roles in cellular biochemistry, proline can be considered as a functional amino acid for mammalian, avian, and aquatic species. Further research is warranted to develop effective strategies of dietary supplementation with proline or hydroxyproline to benefit health, growth, and development of animals and humans. PMID:20697752

  4. Telomeres and genomic damage repair. Their implication in human pathology

    International Nuclear Information System (INIS)

    Perez, Maria del R.; Dubner, Diana; Michelin, Severino; Gisone, Pablo; Carosella, Edgardo D.

    2002-01-01

    Telomeres, functional complexed that protect eukaryotic chromosome ends, participate in the regulation of cell proliferation and could play a role in the stabilization of genomic regions in response to genotoxic stress. Their significance in human pathology becomes evident in several diseases sharing genomic instability as a common trait, in which alterations of the telomere metabolism have been demonstrated. Many of them are also associated with hypersensitivity to ionizing radiation and cancer susceptibility. Besides the specific proteins belonging to the telomeric complex, other proteins involved in the DNA repair machinery, such as ATM, BRCA1, BRCA2, PARP/tankyrase system, DNA-PK and RAD50-MRE11-NBS1 complexes, are closely related with the telomere. This suggests that the telomere sequesters DNA repair proteins for its own structure maintenance, with could also be released toward damaged sites in the genomic DNA. This communication describes essential aspects of telomere structure and function and their links with homologous recombination, non-homologous end-joining (NHEJ), V(D)J system and mismatch-repair (MMR). Several pathological conditions exhibiting alterations in some of these mechanisms are also considered. The cell response to ionizing radiation and its relationship with the telomeric metabolism is particularly taken into account as a model for studying genotoxicity. (author)

  5. [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. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  6. General Psychological Implications of the Human Capacity for Grief.

    Science.gov (United States)

    Brinkmann, Svend

    2018-06-01

    Much theorizing in psychology and related disciplines begins with a given model of the mind that is then applied in research projects to study concrete phenomena. Sometimes psychological research can be theory-driven in quite an explicit way, approaching the logic of the hypothetico-deductive method. Others reject this and prefer to work inductively, and, in the extreme case of positivism, perhaps try to avoid theorizing altogether. In this article I shall suggest another way to think of the relationship between psychological theories and psychological phenomena. My suggestion is not simply to replace the hypothetico-deductive model with an inductive one, but to argue that the most direct route to theories of the human mind that grasp its complexity is to begin with the Kantian question of transcendental philosophy: X exists - how is X possible? In the context of this article, I apply this questioning to the phenomenon of grief: Grief exists - what general psychological theory of the mind do we need in order to account for its possibility? I attempt to extract three general psychological points from the existence of grief, viz. (1) the deep relationality of the self, (2) the limitations of evolutionary accounts, and (3) the normativity of psychological phenomena. I shall argue that these are general psychological lessons to be learned from grief, although they could also be arrived at by considering several other significant psychological phenomena.

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

    OpenAIRE

    Marina Verga; Manuela Michelazzi

    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...

  8. Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

    Science.gov (United States)

    Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

    2013-01-01

    Abstract Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful. Antioxid. Redox Signal. 19, 192–208 PMID:23198849

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

    OpenAIRE

    Gawlik, Remigiusz; Jacobsen, Gorm

    2016-01-01

    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 se...

  10. Potential risks of nanotechnology to humans and environment: implications and response mechanisms in Africa

    CSIR Research Space (South Africa)

    Musee, N

    2011-11-01

    Full Text Available and Nanotechnology Summer School Pretoria, South Africa, 22nd NOV? 2nd DEC 2009 Potential risks of nanotechnology to humans and the environment: implications and response mechanisms in Africa Ndeke Musee, Lucky Sikhwivhilu, Nomakhwezi Nota, Lisa Schaefer... COVISET Conference, Johannesburg, South Africa, 22-25 Nov 2011? CSIR 2006 www.csir.co.za Effect of SWCNT on Eschericia coli (a) SEM image of E. Coli incubated without SWCNTs for 60 min. [Source: Kang et al. / Langmuir 2007, 23...

  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. The Human Rights Act: What are the implications for older people?

    Science.gov (United States)

    2001-06-01

    Help the Aged is launching a report outlining the terms of the Human Rights Act and its implications both for older people themselves and for public bodies responsible for providing services to them. Tessa Harding, head of policy at Help the Aged said: 'The Human Rights Act is an important turning point for older people. Not only does it establish key rights of individuals to freedom from inhuman and degrading treatment, to private and family life and so on; it also prohibits discrimination in accessing these rights.We expect older people and their advocates to use the Act to ensure greater fairness and equality in our society.'

  13. An examination of human factors in external beam radiation therapy: Findings and implications

    International Nuclear Information System (INIS)

    Henriksen, K.; Kaye, R.D.; Jones, R.E. Jr.; Morisseau, D.S.; Persensky, J.J.

    1994-01-01

    To better understand the contributing factors to human error in external beam radiation therapy, the US Nuclear Regulatory Commission has undertaken a series of human factors evaluations. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation technologists, conducted visits to 24 radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was initially performed to guide subsequent evaluations in the areas of human-system interfaces, procedures, training and qualifications, and organizational policies and practices. Representative findings and implications for improvement are discussed within the context of a dynamic model which holds that misadministration likely results from the unanticipated interaction of several necessary but singly insufficient conditions

  14. Differentiating human versus non-human bone by exploring the nutrient foramen: implications for forensic anthropology.

    Science.gov (United States)

    Johnson, Vail; Beckett, Sophie; Márquez-Grant, Nicholas

    2017-11-01

    One of the roles of a forensic anthropologist is to assist medico-legal investigations in the identification of human skeletal remains. In some instances, only small fragments of bone may be present. In this study, a non-destructive novel technique is presented to distinguish between human and non-human long bones. This technique is based on the macroscopic and computed tomography (CT) analysis of nutrient foramina. The nutrient foramen of long bone diaphyses transmits the nutrient artery which provides much of the oxygen and nutrients to the bone. The nutrient foramen and its canal were analysed in six femora and humeri of human, sheep (Ovies aries) and pig (Sus scrofa) species. The location, position and direction of the nutrient foramina were measured macroscopically. The length of the canal, angle of the canal, circumference and area of the entrance of the foramen were measured from CT images. Macroscopic analysis revealed the femora nutrient foramina are more proximal, whereas humeri foramina are more distal. The human bones and sheep humerus conform to the perceived directionality, but the pig bones and sheep femur do not. Amongst the parameters measured in the CT analysis, the angle of the canal had a discriminatory power. This study shows the potential of this technique to be used independently or complementary to other methods in distinguishing between human and non-human bone in forensic anthropology.

  15. Inactivation of high-risk human papillomaviruses by Holder pasteurization: implications for donor human milk banking.

    Science.gov (United States)

    Donalisio, Manuela; Cagno, Valeria; Vallino, Marta; Moro, Guido E; Arslanoglu, Sertac; Tonetto, Paola; Bertino, Enrico; Lembo, David

    2014-01-01

    Several studies have recently reported the detection of oncogenic human papillomaviruses (HPV) in human milk of a minority of lactating mothers. These findings raised safety concerns in the context of human donor milk banking given the potential risk of HPV transmission to recipient infants. The aim of this study was to investigate whether the Holder pasteurization, a procedure currently in use in human donor milk banks for milk pasteurization, completely inactivates high-risk and low-risk HPV. HPV pseudoviruses (PsV) were generated, spiked into cell culture medium or donor human milk and subjected to thermal inactivation. HPV PsV infectivity and morphological integrity was analyzed by cell-based assay and by electron microscopy, respectively. The Holder pasteurization completely inactivated the infectivity of high-risk (types 16 and 18) and low-risk (type 6) HPV both in cell culture medium and in human milk causing PsV particle disassembly. The results presented here indicate that the Holder pasteurization is an efficient procedure to inactivate high-risk and low-risk HPV thus preventing the potential risk of their transmission through human donor milk.

  16. 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.

  17. 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.

  18. Unpasteurized Shared Human Milk Use in Pediatric Inpatients: Health and Ethical Implications.

    Science.gov (United States)

    Barbas, Kimberly H; Sussman-Karten, Karen; Kamin, Daniel; Huh, Susanna Y

    2017-06-01

    Growing evidence supporting the health benefits of human milk, particularly in the preterm population, has led to rising demand for donor human milk in NICUs and pediatric hospitals. There are no previous reports describing the use of unpasteurized shared human milk (USHM) in the hospital setting, but the use of USHM solicited from community donors through social networks appears to be common. Many pediatric hospitals permit inpatients to receive breast milk that has been screened and pasteurized by a human milk banking organization and will provide pasteurized donor human milk (PDHM) only to infants who are preterm or have specific medical conditions. These policies are designed to minimize potential adverse effects from improperly handled or screened donor milk and to target patients who would experience the greatest benefit in health outcomes with donor milk use. We explore the ethical and health implications of 2 cases of medically complex infants who did not meet criteria in our tertiary care hospital for the use of PDHM from a regulated human milk bank and were incidentally found to be using USHM. These cases raise questions about how best to balance the ethical principles of beneficence, nonmaleficence, justice, and patient autonomy in the provision of PDHM, a limited resource. Health care staff should ask about USHM use to provide adequate counseling about the risks and benefits of various feeding options in the context of an infant's medical condition. Copyright © 2017 by the American Academy of Pediatrics.

  19. "implicate Order" and the Good Life: Applying David Bohm's Ontology in Human World

    Science.gov (United States)

    Ravn, Ib.

    In an attempt to formulate a coherent view of quantum reality, the theoretical physicist David Bohm has proposed a new concept of order to supplement the mechanistic Cartesian order of traditional physics. The "implicate" order is a subtler and deeper order that emphasizes "unbroken wholeness in flowing movement," in contrast to the coarser and more superficial, "explicate" Cartesian order of distinct phenomena. This dissertation attempts to develop a meaning for the idea of implicate order in the world of human experience. First is offered an account of some evolutionary episodes in terms of implicate and explicate order which draws on compatible work in cosmology, embryogenesis, visual perception, brain memory, decision making and phenomenology. Two important characteristics of the implicate order are then identified: in an implicate order, the whole is enfolded (or represented) in its parts; and all parts render different perspectives of the whole. Using arguments from decision making, the study of "flow" in human consciousness, and a model of skill acquisition, it is suggested that these characteristics manifest themselves in the human world as the "unity experience" and the "diversity experience," respectively. The former is the experience that a given part of one's life reveals a larger wholeness or unity; the subject-object distinction is transcended and one becomes absorbed in the flow of whatever activity is pursued. The latter is a deep appreciation of the diversity of ways in which people may seek the unity experience. These experiences are proposed as general values: social and psychological conditions ought to be such that these experiences are enhanced in all people. A two-by-two matrix of the two experiences demonstrates the danger of pursuing one to the exclusion of the other. The experience of unity without diversity turns into absolutism, the insistence that one's chosen activities or beliefs are the only right ones. The experience of diversity

  20. Glis family proteins are differentially implicated in the cellular reprogramming of human somatic cells.

    Science.gov (United States)

    Lee, Seo-Young; Noh, Hye Bin; Kim, Hyeong-Taek; Lee, Kang-In; Hwang, Dong-Youn

    2017-09-29

    The ground-breaking discovery of the reprogramming of somatic cells into pluripotent cells, termed induced pluripotent stem cells (iPSCs), was accomplished by delivering 4 transcription factors, Oct4, Sox2, Klf4, and c-Myc, into fibroblasts. Since then, several efforts have attempted to unveil other factors that are directly implicated in or might enhance reprogramming. Importantly, a number of transcription factors are reported to retain reprogramming activity. A previous study suggested Gli-similar 1 (Glis1) as a factor that enhances the reprogramming of fibroblasts during iPSC generation. However, the implication of other Glis members, including Glis2 and Glis3 (variants 1 and 2), in cellular reprogramming remains unknown. In this study, we investigated the potential involvement of human Glis family proteins, including hGlis1-3, in cellular reprogramming. Our results demonstrate that hGlis1, which is reported to reprogram human fibroblasts, promotes the reprogramming of human adipose-derived stromal cells (hADSCs), indicating that the reprogramming activity of Glis1 is not cell type-specific. Strikingly, hGlis3 promoted the reprogramming of hADSCs as efficiently as hGlis1. On the contrary, hGlis2 showed a strong negative effect on reprogramming. Together, our results reveal clear differences in the cellular reprogramming activity among Glis family members and provide valuable insight into the development of a new reprogramming strategy using Glis family proteins.

  1. 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

  2. Progress in understanding human ovarian folliculogenesis and its implications in assisted reproduction.

    Science.gov (United States)

    Yang, Dong Zi; Yang, Wan; Li, Yu; He, Zuanyu

    2013-02-01

    To highlight recent progress in understanding the pattern of follicular wave emergence of human menstrual cycle, providing a brief overview of the new options for human ovarian stimulation and oocyte retrieval by making full use of follicular physiological waves of the patients either with normal or abnormal ovarian reserve. Literature review and editorial commentary. There has been increasing evidence to suggest that multiple (two or three) antral follicular waves are recruited during human menstrual cycle. The treatment regimens designed based on the theory of follicular waves, to promote increased success with assisted reproduction technology (ART) and fertility preservation have been reported. These new options for human ovarian stimulation and oocyte retrieval by making full use of follicular waves of the patients either with normal or abnormal ovarian reserve lead to new thinking about the standard protocols in ART and challenge the traditional theory that a single wave of antral follicles grows only during the follicular phase of the menstrual cycle. The understanding of human ovarian folliculogenesis may have profound implications in ART and fertility preservation. Further studies are needed to evaluate the optimal regimens in ART based on the theory of follicular waves and to identify non-invasive markers for predicting the outcome and the potential utilities of follicles obtained from anovulatory follicular waves in ART.

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

    Directory of Open Access Journals (Sweden)

    Tom J Coulthard

    Full Text Available 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.

  4. 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...

  5. 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. © 2014 International Union of Psychological Science.

  6. 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.......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...

  7. Genetic testing and its implications: human genetics researchers grapple with ethical issues.

    Science.gov (United States)

    Rabino, Isaac

    2003-01-01

    To better understand ethical issues involved in the field of human genetics and promote debate within the scientific community, the author surveyed scientists who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. This study contributes systematic data on attitudes of scientific experts. The survey finds respondents are highly supportive of voluntary testing and the right to know one's genetic heritage. The majority consider in utero testing and consequent pregnancy termination acceptable for cases involving likelihood of serious disease but disapprove for genetic reasons they consider arbitrary, leaving a gray area of distinguishing between treatment of disorders and enhancement still to be resolved. While safeguarding patient confidentiality versus protecting at-risk third parties (kin, reproductive partners) presents a dilemma, preserving privacy from misuse by institutional third parties (employers, insurers) garners strong consensus for legislation against discrimination. Finally, a call is made for greater genetic literacy.

  8. 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.

  9. 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…

  10. Matrigel alters the pathophysiology of orthotopic human breast adenocarcinoma xenografts with implications for nanomedicine evaluation.

    Science.gov (United States)

    Shuhendler, Adam J; Prasad, Preethy; Cai, Ping; Hui, Kelvin K W; Henderson, Jeffrey T; Rauth, Andrew M; Wu, Xiao Yu

    2013-08-01

    Matrigel, a mouse sarcoma-derived basement membrane protein mixture, is frequently used to facilitate human tumor xenograft growth in rodents. Despite its known effects on tumor growth and metastasis, its impact on tumor pathophysiology and preclinical evaluation of nanomedicines in tumor xenografts has not been reported previously. Herein bilateral MDA435 tumors were established orthotopically with (Mat+) or without (Mat-) co-injection of Matrigel. Tumor perfusion, morphology and nanoparticle retention were evaluated. As compared to Mat- tumors, Mat+tumors exhibited enhanced vascular perfusion and lymphatic flow, greater blood vessel and lymphatic growth within the tumor core, and more deformation and collapse of lymphatics in tumor-associated lymph nodes. These changes were accompanied by reduced nanoparticle retention in Mat+tumors. The results suggest that Matrigel is not a passive medium for tumor growth, but rather significantly alters long-term tumor architecture. These findings have significant implications for the evaluation of therapeutic nanomedicine in xenograft mouse models. Matrigel is utilized in facilitating human tumor xenograft growth in rodents. The authors demonstrate that Matrigel is not a passive medium for tumor growth; instead it significantly alters long-term tumor architecture, with major implications in the evaluation of therapeutic nanomedicine in xenograft mouse models. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Variation in macronutrients in human bank milk: Influencing factors and implications for human milk banking

    DEFF Research Database (Denmark)

    Michaelsen, K F; Skafte, Ester Lis; Badsberg, Jens Henrik

    1990-01-01

    . There was a large variation in the concentration of energy-yielding macronutrients. The contents of P, F, C, and E in the samples with the highest values (97.5 percentile) were 2.3-, 4.8-, 1.2-, and 2.3-fold, respectively, above the contents in the samples with the lowest values (2.5 percentile). The P content...... decreased exponentially during the 1st 8 months, followed by an increase during the following months. The F content decreased during the 1st 4 months, followed by an almost linear increase. The possible influence of different maternal characteristics on the macronutrient content of the milk was examined...... 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...

  12. Implications of leading crop production practices on environmental quality and human health.

    Science.gov (United States)

    Udeigwe, Theophilus K; Teboh, Jasper M; Eze, Peter N; Stietiya, M Hashem; Kumar, Vipan; Hendrix, James; Mascagni, Henry J; Ying, Teng; Kandakji, Tarek

    2015-03-15

    Globally, much weight is currently being placed on agriculture to provide food for the growing population as well as feedstock for the bioenergy industry. Unfortunately, the intensification of agricultural operations to satisfy these growing needs has been associated with a number of environmental and human health risks. A review of publications on the subject was conducted and emphasis was placed on articles focusing on agriculture, environment, and public health as well as their interactions. Supporting information was also gathered from publications of various agricultural and environmental agencies. Agricultural practices with potential negative implications on the environment and human health were identified broadly as: (a) utilization of biosolids and animal manures, (b) use of agricultural chemicals, (c) management of post-harvest residue, (d) irrigation, and (e) tillage operations. Soil, water, and air contamination by nutrients, heavy metals, pathogens, and pesticides, as well as air contamination by particulate matters, noxious gases, and pathogens were among the leading environmental impacts. Some of the human-health impacts identified included neurological and reproductive defects, cardiovascular risks, cancers and other diseases (of kidney, liver, lung, and skin), skin allergies, gastroenteritis, and methemoglobinemia. Continual awareness on the impacts of the reviewed agricultural practices on environmental quality and human health and the implementation of experimentally-backed best management practices in agricultural systems remain indispensable. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Toxicological Implications and Inflammatory Response in Human Lymphocytes Challenged with Oxytetracycline.

    Science.gov (United States)

    Di Cerbo, A; Palatucci, A T; Rubino, V; Centenaro, S; Giovazzino, A; Fraccaroli, E; Cortese, L; Ruggiero, G; Guidetti, G; Canello, S; Terrazzano, G

    2016-04-01

    Antibiotics are widely used in zoo technical and veterinary practices as feed supplementation to ensure wellness of farmed animals and livestock. Several evidences have been suggesting both the toxic role for tetracyclines, particularly for oxytetracycline (OTC). This potential toxicity appears of great relevance for human nutrition and for domestic animals. This study aimed to extend the evaluation of such toxicity. The biologic impact of the drug was assessed by evaluating the proinflammatory effect of OTC and their bone residues on cytokine secretion by in vitro human peripheral blood lymphocytes. Our results showed that both OTC and OTC-bone residues significantly induced the T lymphocyte and non-T cell secretion of interferon (IFN)-γ, as cytokine involved in inflammatory responses in humans as well as in animals. These results may suggest a possible implication for new potential human and animal health risks depending on the entry of tetracyclines in the food-processing chain. © 2015 The Authors Journal of Biochemical and Molecular Toxicology Published Wiley Periodicals, Inc.

  14. 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.

  15. The western lowland gorilla diet has implications for the health of humans and other hominoids.

    Science.gov (United States)

    Popovich, D G; Jenkins, D J; Kendall, C W; Dierenfeld, E S; Carroll, R W; Tariq, N; Vidgen, E

    1997-10-01

    We studied the western lowland gorilla diet as a possible model for human nutrient requirements with implications for colonic function. Gorillas in the Central African Republic were identified as consuming over 200 species and varieties of plants and 100 species and varieties of fruit. Thirty-one of the most commonly consumed foods were collected and dried locally before shipping for macronutrient and fiber analysis. The mean macronutrient concentrations were (mean +/- SD, g/100 g dry basis) fat 0.5 +/- 0.4, protein 11.8 +/- 8.2, available carbohydrate 7.7 +/- 6.3 and dietary fiber 74.0 +/- 12.9. Assuming that the macronutrient profile of these foods was reflective of the whole gorilla diet and that dietary fiber contributed 6.28 kJ/g (1.5 kcal/g), then the gorilla diet would provide 810 kJ (194 kcal) metabolizable energy per 100 g dry weight. The macronutrient profile of this diet would be as follows: 2.5% energy as fat, 24.3% protein, 15.8% available carbohydrate, with potentially 57.3% of metabolizable energy from short-chain fatty acids (SCFA) derived from colonic fermentation of fiber. Gorillas would therefore obtain considerable energy through fiber fermentation. We suggest that humans also evolved consuming similar high foliage, high fiber diets, which were low in fat and dietary cholesterol. The macronutrient and fiber profile of the gorilla diet is one in which the colon is likely to play a major role in overall nutrition. Both the nutrient and fiber components of such a diet and the functional capacity of the hominoid colon may have important dietary implications for contemporary human health.

  16. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

    Science.gov (United States)

    Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

    2017-01-01

    The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  17. Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia.

    Science.gov (United States)

    Lunetti, Paola; Damiano, Fabrizio; De Benedetto, Giuseppe; Siculella, Luisa; Pennetta, Antonio; Muto, Luigina; Paradies, Eleonora; Marobbio, Carlo Marya Thomas; Dolce, Vincenza; Capobianco, Loredana

    2016-09-16

    Heme is an essential molecule in many biological processes, such as transport and storage of oxygen and electron transfer as well as a structural component of hemoproteins. Defects of heme biosynthesis in developing erythroblasts have profound medical implications, as represented by sideroblastic anemia. The synthesis of heme requires the uptake of glycine into the mitochondrial matrix where glycine is condensed with succinyl coenzyme A to yield δ-aminolevulinic acid. Herein we describe the biochemical and molecular characterization of yeast Hem25p and human SLC25A38, providing evidence that they are mitochondrial carriers for glycine. In particular, the hem25Δ mutant manifests a defect in the biosynthesis of δ-aminolevulinic acid and displays reduced levels of downstream heme and mitochondrial cytochromes. The observed defects are rescued by complementation with yeast HEM25 or human SLC25A38 genes. Our results identify new proteins in the heme biosynthetic pathway and demonstrate that Hem25p and its human orthologue SLC25A38 are the main mitochondrial glycine transporters required for heme synthesis, providing definitive evidence of their previously proposed glycine transport function. Furthermore, our work may suggest new therapeutic approaches for the treatment of congenital sideroblastic anemia. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  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. Land use change in China: implication for human-environmental interactions

    Science.gov (United States)

    cui, Xuefeng

    2013-04-01

    China's land use has undergone significant changes in history due to the continuous transformations caused by natural and human factors. This paper will review the history of land use changes in China during the past 300 years to identify the major transition periods and discuss the implications for environmental management. Population changes are found to be the primary driving factor in cropland expansion and deforestation in history for a long period. In 1950s, after the foundation of the Republic of China, all land use types experience a huge transition showing the determination of socio-economic policies in modern time after agricultural intensifications. Several current environmental policy in China will also be discussed to explore the effect of policy on land use changes.

  20. 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.

  1. A genetic comparison of human and wildlife isolates of Echinococcus granulosus in Queensland: public health implications.

    Science.gov (United States)

    Hope, M; Bowles, J; Prociv, P; McManus, D P

    1992-01-06

    To test the hypothesis that the hydatid parasite infecting macropods and dingoes in Queensland is a sylvatic strain of Echinococcus granulosus, distinct from the domestic strain which produces cysts in sheep and humans. Molecular biological techniques were used to compare DNA isolated from hydatid cysts from humans, local macropods and sheep from New South Wales and the United Kingdom, as well as from adult tapeworms in dingoes. The human cysts were surgically resected from two patients seen with hydatidosis in Brisbane teaching hospitals over a one-year period. Neither patient had had previous contact with sheep farms. Macropods and dingoes were shot randomly in the localities where the patients presumably acquired their infections. Sheep liver cysts were obtained from abattoirs. Studies comprised extraction of DNA from cysts, digestion by a series of restriction endonucleases, slab gel electrophoresis. Southern blotting and then hybridisation with defined DNA probes. Polymerase chain reaction, in combination with direct DNA sequencing, was used to compare DNA from cysts and adult worms from dingoes. The restriction fragment length polymorphism (RFLP) patterns of DNA from all cysts and a defined mitochondrial DNA sequence from all sources were indistinguishable. This finding is significant as both techniques can clearly distinguish between genetically distinct, well characterised strains of E. granulosus. Hydatid cysts are prevalent in some macropod populations and adult worms are common in dingoes. Since there are relatively few sheep-rearing areas in Queensland, contact with wild animals may be the main source of human hydatid infection in this State. The strain of E. granulosus in both patients was genetically indistinguishable from that found in macropods, dingoes and sheep from New South Wales and the United Kingdom. This strongly suggests that the domestic strain of E. granulosus, or a form very close genetically, freely infects Australian wildlife, and

  2. The quantitative assessment of epicardial fat distribution on human hearts: Implications for epicardial electrophysiology.

    Science.gov (United States)

    Mattson, Alexander R; Soto, Mario J; Iaizzo, Paul A

    2018-07-01

    Epicardial electrophysiological procedures rely on dependable interfacing with the myocardial tissue. For example, epicardial pacing systems must generate sustainable chronic pacing capture, while epicardial ablations must effectively deliver energy to the target hyper-excitable myocytes. The human heart has a significant adipose layer which may impede epicardial procedures. The objective of this study was to quantitatively assess the relative location of epicardial adipose on the human heart, to define locations where epicardial therapies might be performed successfully. We studied perfusion-fixed human hearts (n = 105) in multiple isolated planes including: left ventricular margin, diaphragmatic surface, and anterior right ventricle. Relative adipose distribution was quantitatively assessed via planar images, using a custom-generated image analysis algorithm. In these specimens, 76.7 ± 13.8% of the left ventricular margin, 72.7 ± 11.3% of the diaphragmatic surface, and 92.1 ± 8.7% of the anterior right margin were covered with superficial epicardial adipose layers. Percent adipose coverage significantly increased with age (P history of coronary artery disease (P history of hypertension, and/or history of congestive heart failure. Additionally, we describe two-dimensional probability distributions of epicardial adipose coverage for each of the three analysis planes. In this study, we detail the quantitative assessment and probabilistic mapping of the distribution of superficial epicardial adipose on the adult human heart. These findings have implications relative to performing epicardial procedures and/or designing procedures or tools to successfully perform such treatments. Clin. Anat. 31:661-666, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  3. 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.

  4. 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.

  5. 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.

  6. 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. Copyright © 2012 SETAC.

  7. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

    Directory of Open Access Journals (Sweden)

    Wen-Yang Tsai

    2017-07-01

    Full Text Available The four serotypes of dengue virus (DENV are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8% in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  8. Risk Assessment and Implication of Human Exposure to Road Dust Heavy Metals in Jeddah, Saudi Arabia.

    Science.gov (United States)

    Shabbaj, Ibrahim I; Alghamdi, Mansour A; Shamy, Magdy; Hassan, Salwa K; Alsharif, Musaab M; Khoder, Mamdouh I

    2017-12-26

    Data dealing with the assessment of heavy metal pollution in road dusts in Jeddah, Saudi Arabia and its implication to human health risk of human exposure to heavy metals, are scarce. Road dusts were collected from five different functional areas (traffic areas (TA), parking areas (PA), residential areas (RA), mixed residential commercial areas (MCRA) and suburban areas (SA)) in Jeddah and one in a rural area (RUA) in Hada Al Sham. We aimed to measure the pollution levels of heavy metals and estimate their health risk of human exposure applying risk assessment models described by United States Environmental Protection Agency (USEPA). Using geo-accumulation index (I geo ), the pollution level of heavy metals in urban road dusts was in the following order Cd > As > Pb > Zn > Cu > Ni > Cr > V > Mn > Co > Fe. Urban road dust was found to be moderately to heavily contaminated with As, Pb and Zn, and heavily to extremely contaminated with Cd. Calculation of enrichment factor (EF) revealed that heavy metals in TA had the highest values compared to that of the other functional areas. Cd, As, Pb, Zn and Cu were severely enriched, while Mn, V, Co, Ni and Cr were moderately enriched. Fe was considered as a natural element and consequently excluded. The concentrations of heavy metals in road dusts of functional areas were in the following order: TA > PA > MCRA > SA > RA > RUA. The study revealed that both children and adults in all studied areas having health quotient (HQ) exposure route was ingestion. The cancer risk for children and adults from exposure to Pb, Cd, Co, Ni, and Cr was found to be negligible (≤1 × 10 -6 ).

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

  12. Human papillomavirus vaccine and cervical cancer prevention: practice and policy implications for pharmacists.

    Science.gov (United States)

    McIntosh, Jennifer; Sturpe, Deborah A; Khanna, Niharika

    2008-01-01

    To review the epidemiology and natural history of human papillomavirus (HPV), summarize relevant clinical trials of the prophylactic HPV vaccines, and describe the practice and policy implications that HPV vaccine represents for pharmacists. Search of Medline through June 2007 using keywords human papillomavirus vaccine, Gardasil, and Cervarix; meeting abstracts; bibliographies from selected articles; and National Institutes of Health clinical trials registry. English language review articles, clinical trials, and published abstracts were considered for inclusion. HPV is a sexually transmitted infection that is necessary for the development of cervical cancer, and types 16 and 18 are associated with 70% of cases of invasive cervical cancer worldwide. A quadrivalent prophylactic vaccine against HPV-6, -11, -16, and -18 is currently available, and a bivalent vaccine targeting HPV-16 and -18 is under review by the Food and Drug Administration. Both are highly effective at preventing persistent HPV infection and precancerous lesions caused by vaccine-specific HPV. HPV vaccine is currently indicated for girls aged 9 to 26 years, but ongoing trials are evaluating the efficacy in other populations. Implementation of a vaccine administration program is an area of opportunity for new policies to include pharmacists in the administration of prophylactic HPV vaccines. Pharmacists are allowed to administer vaccinations in 46 states and can potentially play a role in HPV vaccine administration. For this to happen, however, multiple legal and regulatory changes must occur. Prophylactic HPV vaccines safely and effectively prevent HPV infection and precancerous lesions in the cervix. The availability of these vaccines also create new clinical opportunities for community pharmacists, provided needed legal, regulatory, and policy changes are made.

  13. UV-associated decline in systemic folate: implications for human nutrigenetics, health, and evolutionary processes.

    Science.gov (United States)

    Lucock, Mark; Beckett, Emma; Martin, Charlotte; Jones, Patrice; Furst, John; Yates, Zoe; Jablonski, Nina G; Chaplin, George; Veysey, Martin

    2017-03-01

    The purpose of this study was to examine whether UV exposure alters folate status according to C677T-MTHFR genotype, and to consider the relevance of this to human health and the evolutionary model of skin pigmentation. Total Ozone Mapping Spectrometer (TOMS) satellite data were used to examine surface UV-irradiance, as a marker of UV exposure, in a large (n = 649) Australian cross-sectional study population. PCR/RFLP analysis was used to genotype C677T-MTHFR. Overall, cumulative UV-irradiance (42 and 120 days pre-clinic) was significantly negatively related to red cell folate (RCF) levels. When the cohort was stratified by MTHFR-C677T genotype, the relationship between UV-irradiance (42 days pre-clinic) and RCF remained significant only in the cohorts containing carriers of the T allele. Statistically significant z-score statistics and interaction terms from genotype and UV-irradiance (p-interaction) demonstrated that genotype did modify the effect of UV-irradiance on RCF, with the largest effect of UV being demonstrated in the 677TT-MTHFR subjects. Data provide strong evidence that surface UV-irradiance reduces long-term systemic folate levels, and that this is influenced by the C677T-MTHFR gene variant. We speculate this effect may be due to 677TT-MTHFR individuals containing more 5,10CH 2 -H 4 PteGlu, and that this folate form may be particularly UV labile. Since UV-irradiance lowers RCF in an MTHFR genotype-specific way, there are likely implications for human health and the evolution of skin pigmentation. © 2016 Wiley Periodicals, Inc.

  14. 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.

  15. BIOETHICS METHODS IN THE ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS OF THE HUMAN GENOME PROJECT LITERATURE

    Science.gov (United States)

    Walker, Rebecca; Morrissey, Clair

    2013-01-01

    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 2003-2008 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). PMID:23796275

  16. Fungal spore germination into yeast or mycelium: possible implications of dimorphism in evolution and human pathogenesis

    Science.gov (United States)

    Ghormade, Vandana; Deshpande, M. V.

    The ability of dimorphism in fungi is conventionally regarded as a reversible change between the two vegetative forms, yeast and mycelium, in response to environmental change. A zygomycetous isolate, Benjaminiella poitrasii, exhibited yeast-mycelium transition in response to the change in temperature (37-28 °C) and decrease in glucose concentration. For the first time the presence of dimorphic response during asexual and sexual spore germination is reported under the dimorphism-triggering conditions in B. poitrasii. The zygospores germinated into budding yeast when subjected to yeast-form supporting conditions. The mycelium-form favoring conditions gave rise to true mycelium. Similarly, the asexual spores displayed a dimorphic response during germination. Our observations suggest that dimorphism is an intrinsic ability present in the vegetative, asexual, and sexual forms of the fungus. As dimorphic fungi are intermediate to the unicellular yeast and the filamentous forms, understanding of the dimorphic character could be useful to trace the evolutionary relationships among taxonomically different fungi. Moreover, the implications of spore germination during the onset of pathogenesis and in drug development for human health care are discussed.

  17. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. 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.

  19. PKCε promotes human Th17 differentiation: Implications in the pathophysiology of psoriasis.

    Science.gov (United States)

    Martini, Silvia; Pozzi, Giulia; Carubbi, Cecilia; Masselli, Elena; Galli, Daniela; Di Nuzzo, Sergio; Banchini, Antonio; Gobbi, Giuliana; Vitale, Marco; Mirandola, Prisco

    2018-04-01

    PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4 + -T cells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4 + -T cells from patients with psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4 + subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: (i) PKCε is overexpressed in CD4 + -T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4 + -T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Inhibition of human UDP-glucuronosyltransferase enzymes by lapatinib, pazopanib, regorafenib and sorafenib: Implications for hyperbilirubinemia.

    Science.gov (United States)

    Miners, John O; Chau, Nuy; Rowland, Andrew; Burns, Kushari; McKinnon, Ross A; Mackenzie, Peter I; Tucker, Geoffrey T; Knights, Kathleen M; Kichenadasse, Ganessan

    2017-04-01

    Kinase inhibitors (KIs) are a rapidly expanding class of drugs used primarily for the treatment of cancer. Data relating to the inhibition of UDP-glucuronosyltransferase (UGT) enzymes by KIs is sparse. However, lapatinib (LAP), pazopanib (PAZ), regorafenib (REG) and sorafenib (SOR) have been implicated in the development of hyperbilirubinemia in patients. This study aimed to characterise the role of UGT1A1 inhibition in hyperbilirubinemia and assess the broader potential of these drugs to perpetrate drug-drug interactions arising from UGT enzyme inhibition. Twelve recombinant human UGTs from subfamilies 1A and 2B were screened for inhibition by LAP, PAZ, REG and SOR. IC 50 values for the inhibition of all UGT1A enzymes, except UGT1A3 and UGT1A4, by the four KIs were enzyme identified to date. In vitro-in vivo extrapolation indicates that inhibition of UGT1A1 contributes significantly to the hyperbilirubinemia observed in patients treated with REG and SOR, but not with LAP and PAZ. Inhibition of other UGT1A1 substrates in vivo is likely. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Lead (Pb) in sheep exposed to mining pollution: implications for animal and human health.

    Science.gov (United States)

    Pareja-Carrera, Jennifer; Mateo, Rafael; Rodríguez-Estival, Jaime

    2014-10-01

    Livestock from the ancient mining area of Sierra Madrona and Alcudia Valley (Spain) is exposed to elevated levels of lead (Pb), as previous studies based on blood monitoring have revealed. Here we have studied blood, liver and muscle Pb levels in sheep in order to know if Pb exposure could represent a risk for human consumers of the meat and offal of these animals. A cross-sectional study was conducted with ≥4 years old (adults) ewes from the mining area (n=46) and a control area (n=21). Blood samples were taken before the sacrifice at the slaughterhouse, and liver and muscle samples were taken thereafter. At the same time, 2-3 year old rams (subadults, n=17) were blood sampled in the mining area. Blood, liver and muscle Pb levels were higher in the mining than in the control area. Blood Pb concentration in the mining area (n= 44, mean: 6.7μg/dl in ewes and 10.9μg/dl in rams) was above background levels (>6μg/dl) in 73.3 percent of animals. Liver Pb concentration in 68 percent of sheep from the mining area (n=32, mean: 6.16μg/g dry weight, d.w.) exceeded the minimum level associated with toxic exposure (5µg/g d.w.) and 87.5 percent of liver samples were above European Union Maximum Residue Levels (MRL) established for offal destined for human consumption (0.5µg/g w.w.~1.4µg/g d.w.). On the contrary, none of the muscle samples in ewes exceeded the EU MRL (0.1µg/g w.w.~0.34µg/g d.w.) established for meat, which may be related to the decline of blood Pb levels with age observed in the present study. These results suggest a potential health effect for sheep exposed to Pb pollution in this area and implications for food safety, but further research with lamb meat may be necessary to refine the risk assessment for human consumers. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Structural Basis for Escape of Human Astrovirus from Antibody Neutralization: Broad Implications for Rational Vaccine Design

    Energy Technology Data Exchange (ETDEWEB)

    Bogdanoff, Walter A.; Perez, Edmundo I.; López, Tomás; Arias, Carlos F.; DuBois, Rebecca M. (UNAM-Mexico); (UCSC)

    2017-10-25

    ABSTRACT

    Human astroviruses are recognized as a leading cause of viral diarrhea worldwide in children, immunocompromised patients, and the elderly. There are currently no vaccines available to prevent astrovirus infection; however, antibodies developed by healthy individuals during previous infection correlate with protection from reinfection, suggesting that an effective vaccine could be developed. In this study, we investigated the molecular mechanism by which several strains of human astrovirus serotype 2 (HAstV-2) are resistant to the potent HAstV-2-neutralizing monoclonal antibody PL-2 (MAb PL-2). Sequencing of the HAstV-2 capsid genes reveals mutations in the PL-2 epitope within the capsid's spike domain. To understand the molecular basis for resistance from MAb PL-2 neutralization, we determined the 1.35-Å-resolution crystal structure of the capsid spike from one of these HAstV-2 strains. Our structure reveals a dramatic conformational change in a loop within the PL-2 epitope due to a serine-to-proline mutation, locking the loop in a conformation that sterically blocks binding and neutralization by MAb PL-2. We show that mutation to serine permits loop flexibility and recovers MAb PL-2 binding. Importantly, we find that HAstV-2 capsid spike containing a serine in this loop is immunogenic and elicits antibodies that neutralize all HAstV-2 strains. Taken together, our results have broad implications for rational selection of vaccine strains that do not contain prolines in antigenic loops, so as to elicit antibodies against diverse loop conformations.

    IMPORTANCEHuman astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. In this study, we investigated how several strains of HAstV are resistant to a virus-neutralizing monoclonal antibody. We determined the crystal structure of the capsid protein spike domain from one of these HAstV strains and found that

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

    Science.gov (United States)

    2013-01-01

    Background 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). Methods 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. Results 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. Conclusions 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

  4. 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

  5. Human GH Receptor-IGF-1 Receptor Interaction: Implications for GH Signaling

    Science.gov (United States)

    Gan, Yujun; Buckels, Ashiya; Liu, Ying; Zhang, Yue; Paterson, Andrew J.; Jiang, Jing; Zinn, Kurt R.

    2014-01-01

    GH signaling yields multiple anabolic and metabolic effects. GH binds the transmembrane GH receptor (GHR) to activate the intracellular GHR-associated tyrosine kinase, Janus kinase 2 (JAK2), and downstream signals, including signal transducer and activator of transcription 5 (STAT5) activation and IGF-1 gene expression. Some GH effects are partly mediated by GH-induced IGF-1 via IGF-1 receptor (IGF-1R), a tyrosine kinase receptor. We previously demonstrated in non-human cells that GH causes formation of a GHR-JAK2-IGF-1R complex and that presence of IGF-1R (even without IGF-1 binding) augments proximal GH signaling. In this study, we use human LNCaP prostate cancer cells as a model system to further study the IGF-1R's role in GH signaling. GH promoted JAK2 and GHR tyrosine phosphorylation and STAT5 activation in LNCaP cells. By coimmunoprecipitation and a new split luciferase complementation assay, we find that GH augments GHR/IGF-1R complex formation, which is inhibited by a Fab of an antagonistic anti-GHR monoclonal antibody. Short hairpin RNA-mediated IGF-1R silencing in LNCaP cells reduced GH-induced GHR, JAK2, and STAT5 phosphorylation. Similarly, a soluble IGF-1R extracellular domain fragment (sol IGF-1R) interacts with GHR in response to GH and blunts GH signaling. Sol IGF-1R also markedly inhibits GH-induced IGF-1 gene expression in both LNCaP cells and mouse primary osteoblast cells. On the basis of these and other findings, we propose a model in which IGF-1R augments GH signaling by allowing a putative IGF-1R-associated molecule that regulates GH signaling to access the activated GHR/JAK2 complex and envision sol IGF-1R as a dominant-negative inhibitor of this IGF-1R-mediated augmentation. Physiological implications of this new model are discussed. PMID:25211187

  6. 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. © 2012 Diabetes Technology Society.

  7. 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…

  8. Human papilloma virus (HPV) prophylactic vaccination: challenges for public health and implications for screening.

    Science.gov (United States)

    Adams, M; Jasani, B; Fiander, A

    2007-04-20

    Prophylactic vaccination against high risk human papilloma virus (HPV) 16 and 18 represents an exciting means of protection against HPV related malignancy. However, this strategy alone, even if there is a level of cross protection against other oncogenic viruses, cannot completely prevent cervical cancer. In some developed countries cervical screening programmes have reduced the incidence of invasive cervical cancer by up to 80% although this decline has now reached a plateau with current cancers occurring in patients who have failed to attend for screening or where the sensitivity of the tests have proved inadequate. Cervical screening is inevitably associated with significant anxiety for the many women who require investigation and treatment following abnormal cervical cytology. However, it is vitally important to stress the need for continued cervical screening to complement vaccination in order to optimise prevention in vaccinees and prevent cervical cancer in older women where the value of vaccination is currently unclear. It is likely that vaccination will ultimately change the natural history of HPV disease by reducing the influence of the highly oncogenic types HPV 16 and 18. In the long term this is likely to lead to an increase in recommended screening intervals. HPV vaccination may also reduce the positive predictive value of cervical cytology by reducing the number of truly positive abnormal smears. Careful consideration is required to ensure vaccination occurs at an age when the vaccine is most effective immunologically and when uptake is likely to be high. Antibody titres following vaccination in girls 12-16 years have been shown to be significantly higher than in older women, favouring vaccination in early adolescence prior contact with the virus. Highest prevalence rates for HPV infection are seen following the onset of sexual activity and therefore vaccination would need to be given prior to sexual debut. Since 20% of adolescents are sexually

  9. 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.

  10. 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

  11. 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.

  12. The genetics of muscle atrophy and growth: the impact and implications of polymorphisms in animals and humans.

    Science.gov (United States)

    Gordon, Erynn S; Gordish Dressman, Heather A; Hoffman, Eric P

    2005-10-01

    Much of the vast diversity we see in animals and people is governed by genetic loci that have quantitative effects of phenotype (quantitative trait loci; QTLs). Here we review the current knowledge of the genetics of atrophy and hypertrophy in both animal husbandry (meat quantity and quality), and humans (muscle size and performance). The selective breeding of animals for meat has apparently led to a few genetic loci with strong effects, with different loci in different animals. In humans, muscle quantitative trait loci (QTLs) appear to be more complex, with few "major" loci identified to date, although this is likely to change in the near future. We describe how the same phenotypic traits we see as positive, greater lean muscle mass in cattle or a better exercise results in humans, can also have negative "side effects" given specific environmental challenges. We also discuss the strength and limitations of single nucleotide polymorphisms (SNP) association studies; what the reader should look for and expect in a published study. Lastly we discuss the ethical and societal implications of this genetic information. As more and more research into the genetic loci that dictate phenotypic traits become available, the ethical implications of testing for these loci become increasingly important. As a society, most accept testing for genetic diseases or susceptibility, but do we as easily accept testing to determine one's athletic potential to be an Olympic endurance runner, or quarterback on the high school football team.

  13. Using geographical information systems (GIS to examine sanitary implications of rubbish dump locations at human activity centres

    Directory of Open Access Journals (Sweden)

    Lenos Koku Ankrah

    2016-01-01

    Full Text Available This study sought to investigate health risks that refuse dump locations have on people. The global positioning systems (GPS were used to take location coordinates of 28 rubbish dump centers and human activity centers (clinics, restaurants, markets etc spread across a university campus in Ghana. The ArcGIS software was used to plot the coordinates and draw a buffer of 50 meters around the rubbish dump locations (RDL to show the closeness between the dump sites and the human activity centers (HAC, and the sanitary implications of the closeness. More than 90% of the HACs fell within the 50 meters buffer zone of the rubbish dump sites. The findings indicated that some sensitive HACs like food joints, laundries etc. were less than 15 meters from rubbish dump sites. The findings confirmed that the location of rubbish dump sites pose serious threat to the health of the human community in the university. The findings of this study can be used to make evidence- based decisions about possible relocation of rubbish dump containers in the university. This study is also an initiative to set the tone for more detailed research work on the health implications of rubbish disposal management on Ghanaians.

  14. Molecular Epidemiology of Nontyphoidal Salmonella in Poultry and Poultry Products in India: Implications for Human Health

    OpenAIRE

    Saravanan, Sellappan; Purushothaman, Venketaraman; Murthy, Thippichettypalayam Ramasamy Gopala Krishna; Sukumar, Kuppannan; Srinivasan, Palani; Gowthaman, Vasudevan; Balusamy, Mohan; Atterbury, Robert; Kuchipudi, Suresh V.

    2015-01-01

    Human infections with non-typhoidal Salmonella (NTS) serovars are increasingly becoming a threat to human health globally. While all motile Salmonellae have zoonotic potential, Salmonella Enteritidis and Salmonella Typhimurium are most commonly associated with human disease, for which poultry are a major source. Despite the increasing number of human NTS infections, the epidemiology of NTS in poultry in India has not been fully understood. Hence, as a first step, we carried out epidemiologica...

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

    Science.gov (United States)

    Miotto, Olivo; Heiny, A T; Albrecht, Randy; García-Sastre, Adolfo; Tan, Tin Wee; August, J Thomas; Brusic, Vladimir

    2010-02-03

    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. 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. 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 unusually high number of adaptive mutations. However, these mutations appear

  16. 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.

  17. 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...

  18. 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

  19. 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.

  20. Co-occurrence of citrinin and ochratoxin A in rice in Asia and its implications for human health.

    Science.gov (United States)

    Ali, Nurshad

    2018-04-01

    Citrinin (CIT) and ochratoxin A (OTA) are nephrotoxic mycotoxins, produced by several Aspergillus and Penicillium species and their co-occurrence in rice may cause health effects in humans. Rice is an important food crop worldwide and is a major staple food in Asia which may be invaded by CIT and OTA producing fungal spores in the field, during harvest and storage. Humans are exposed to these mycotoxins through ingestion of contaminated rice and other food commodities. Yet, data on the combined presence to these food contaminants are still insufficient to estimate human exposure in Asia. This review describes the prevalence of CIT and OTA in rice in Asia and its implications on human health, which may help in establishing and carrying out proper management strategies against mould development on rice. From the health point of view, combined exposition of CIT and OTA should be a public concern as both are nephrotoxic and long-term exposure can pose detrimental health effects. Thus, it is necessary for local farmers and food factories to implement strict measures and to improve methods for rice preservation during the distribution to consumers, particularly in the markets. Moreover, regular surveys for CIT and OTA occurrence in rice and human biomonitoring are recommended to reduce the health effects in Asian population. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  1. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  2. Pulmonary Inflammatory Responses to Acute Meteorite Dust Exposures - Implications for Human Space Exploration

    Science.gov (United States)

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

    2018-01-01

    New initiatives to send humans to Mars within the next few decades are illustrative of the resurgence of interest in space travel. However, as with all exploration, there are risks. 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.

  3. Human X chromosome inactivation and reactivation: implications for cell reprogramming and disease.

    Science.gov (United States)

    Cantone, Irene; Fisher, Amanda G

    2017-11-05

    X-chromosome inactivation (XCI) is an exemplar of epigenetic regulation that is set up as pluripotent cells differentiate. Once established, XCI is stably propagated, but can be reversed in vivo or by pluripotent reprogramming in vitro Although reprogramming provides a useful model for inactive X (Xi) reactivation in mouse, the relative instability and heterogeneity of human embryonic stem (ES) cells and induced pluripotent stem cells hampers comparable progress in human. Here we review studies aimed at reactivating the human Xi using different reprogramming strategies. We outline our recent results using mouse ES cells to reprogramme female human fibroblasts by cell-cell fusion. We show that pluripotent reprogramming induces widespread and rapid chromatin remodelling in which the human Xi loses XIST and H3K27m3 enrichment and selected Xi genes become reactivated, ahead of mitotic division. Using RNA sequencing to map the extent of human Xi reactivation, and chromatin-modifying drugs to potentiate reactivation, we outline how this approach could be used to better design strategies to re-express human X-linked loci. As cell fusion induces the expression of human pluripotency genes that represent both the 'primed' and 'naive' states, this approach may also offer a fresh opportunity to segregate human pluripotent states with distinct Xi expression profiles, using single-cell-based approaches.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'. © 2017 The Author(s).

  4. 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...

  5. 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.

  6. 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 < 0.05) in the concentration of total protein, lactoferrin, lysozyme, Immunoglobulin A, oligosaccharides and sodium in longitudinal samples of mother's 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. © 2016 John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

    Li, J.T.; Liao, B.; Lan, C.Y.; Qiu, J.W.; Shu, W.S.

    2007-01-01

    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

  8. 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.

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

    Science.gov (United States)

    Li, J T; Liao, B; Lan, C Y; Qiu, J W; Shu, W S

    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.

  10. Human resource management outsourcing in Spanish firms: Evolution over time and implication for devolution

    Directory of Open Access Journals (Sweden)

    Debora Gottardello

    2018-02-01

    Full Text Available Purpose: The paper aim to explore the evolution in the use of HRO in Spanish firms, and determine the differences in the degree of implementation of HRO since 1999 until 2014, and also analyze the relationship between HR outsourcing and devolution of HR responsibilities to line managers in Spanish organizations. Design/methodology/approach: This paper combines quantitative and qualitative methods. Namely the article is based on international Cranet HRM survey data collected from private and public organizations and also interviews with HR external providers. Findings: The analysis of developments, based on the Cranet surveys and interviews with HR external providers shows that during the past few years there has been an increasing use of HRO in parallel with the tendency to devolve more HR responsibility to line managers. Research limitations/implications: The main limitation of this research is the limitation of data about reasons for devolution that the CRANET questionnaire provides. However, the interviews carried out enrich the survey data with qualitative results. Practical implications: The findings can be used to guide management teams in outsourcing and devolution decisions to maximize benefits to their organizations. Originality/value: This paper is about the evolution of HRO in Spain as a European Union country where published research on HRO and also its implications is relatively limited. The originality of this paper is mainly the involvement of line manager in the outsourcing process which have been poorly analyzed until now.

  11. Advanced control rooms and crew performance issues: Implications for human reliability

    International Nuclear Information System (INIS)

    O'Hara, J.M.; Hall, R.E.

    1991-01-01

    Recent trends in advanced control room (ACR) design are considered with respect to their impact on human performance. It is concluded that potentially negative influences exist, however, a variety of factors make it difficult to model, analyze, and quantify these effects for human reliability analyses (HRAs)

  12. New Perspectives on the Brain Lesion Approach - Implications for Theoretical Models of Human Memory.

    NARCIS (Netherlands)

    Irish, Muireann; van Kesteren, M.T.R.

    2017-01-01

    Human lesion studies represent the cornerstone of modern day neuropsychology and provide an important adjunct to functional neuroimaging methods. The study of human lesion groups with damage to distinct regions of the brain permits the identification of underlying mechanisms and structures not only

  13. Natural law theory and its implications for human rights in Nigeria ...

    African Journals Online (AJOL)

    The work attributed the problem of human right violations in Nigeria to illiteracy, disregard for the rule of law, corruption, as well as the erroneous mindset that supposes that what is lawful is not necessarily moral. The work also argued that the latter mindset has culminated in some, thinking that human rights should mean ...

  14. Human tissues in a dish : The research and ethical implications of organoid technology

    NARCIS (Netherlands)

    Bredenoord, Annelien L.; Clevers, Hans; Knoblich, Juergen A.

    2017-01-01

    The ability to generate human tissues in vitro from stem cells has raised enormous expectations among the biomedical research community, patients, and the general public. These organoids enable studies of normal development and disease and allow the testing of compounds directly on human tissue.

  15. Fatty acid oxidation in the human fetus: implications for fetal and adult disease

    NARCIS (Netherlands)

    Oey, Nadia A.; Ruiter, Jos P. N.; Attié-Bitach, Tania; Ijlst, Lodewijk; Wanders, Ronald J. A.; Wijburg, Frits A.

    2006-01-01

    Studies in the last few years have shown a remarkably high activity of fatty acid oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression as well as enzymatic activity of long-chain FAO enzymes in the human embryo and fetus. In this study we show activity of the FAO enzymes

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

    Science.gov (United States)

    Chaminade, Thierry; Zecca, Massimiliano; Blakemore, Sarah-Jayne; Takanishi, Atsuo; Frith, Chris D; Micera, Silvestro; Dario, Paolo; Rizzolatti, Giacomo; Gallese, Vittorio; Umiltà, Maria Alessandra

    2010-07-21

    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. 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. 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. Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.

  17. 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…

  18. 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

  19. 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…

  20. Ethical and social implications of microdosing clinical trial (3). Radiological protection of human subjects in research

    International Nuclear Information System (INIS)

    Kurihara, Chieko

    2008-01-01

    Internal irradiation of human subjects in research is discussed. Radiological protection of human subjects in medical research in a framework of radiation protection is surveyed from a viewpoint of general life-ethics and research-ethics. A workshop 'On the internal irradiation of human subjects' to summarize special and systematic knowledge was organized by Research Center for Radiation Protection, National Institute of Radiological Sciences in the beginning of 2008. Activities of this workshop are introduced. Discussion covers also (1) Research ethics and radiation protection, (2) Fundamentals and applications of risk-benefit assessment, (3) Human subjects risk assessment in ICRP recommendation, (4) Mechanism of human subjects internal irradiation assessment, and (5) Present status and future prospects in Japan. (K.Y.)

  1. 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.

  2. Trophic transfer of microplastics and mixed contaminants in the marine food web and implications for human health.

    Science.gov (United States)

    Carbery, Maddison; O'Connor, Wayne; Palanisami, Thavamani

    2018-06-01

    Plastic litter has become one of the most serious threats to the marine environment. Over 690 marine species have been impacted by plastic debris with small plastic particles being observed in the digestive tract of organisms from different trophic levels. The physical and chemical properties of microplastics facilitate the sorption of contaminants to the particle surface, serving as a vector of contaminants to organisms following ingestion. Bioaccumulation factors for higher trophic organisms and impacts on wider marine food webs remain unknown. The main objectives of this review were to discuss the factors influencing microplastic ingestion; describe the biological impacts of associated chemical contaminants; highlight evidence for the trophic transfer of microplastics and contaminants within marine food webs and outline the future research priorities to address potential human health concerns. Controlled laboratory studies looking at the effects of microplastics and contaminants on model organisms employ nominal concentrations and consequently have little relevance to the real environment. Few studies have attempted to track the fate of microplastics and mixed contaminants through a complex marine food web using environmentally relevant concentrations to identify the real level of risk. To our knowledge, there has been no attempt to understand the transfer of microplastics and associated contaminants from seafood to humans and the implications for human health. Research is needed to determine bioaccumulation factors for popular seafood items in order to identify the potential impacts on human health. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. A comparison of antemortem tooth loss in human hunter-gatherers and non-human catarrhines: implications for the identification of behavioral evolution in the human fossil record.

    Science.gov (United States)

    Gilmore, Cassandra C

    2013-06-01

    Middle and Late Pleistocene fossil hominin specimens with severe antemortem tooth loss are often regarded as evidence for the precocious evolution of human-like behaviors, such as conspecific care or cooking, in ancient hominin species. The goal of this project was to ask whether the theoretical association between antemortem tooth loss and uniquely human behaviors is supported empirically in a large skeletal sample of human hunter-gatherers, chimpanzees, orangutans, and baboons. Binomial regression modeling in a Bayesian framework allows for the investigation of the effects of tooth class, genus, age, and sex on the likelihood of tooth loss. The results strongly suggest that modern humans experience more antemortem tooth loss than non-human primates and identify age in years as an important predictor. Once age is accounted for, the difference between the humans and the closest non-human genus (chimpanzees) is less pronounced; humans are still more likely on average to experience antemortem tooth loss though 95% uncertainty envelopes around the average prediction for each genus show some overlap. These analyses support theoretical links between antemortem tooth loss and modern human characteristics; humans' significantly longer life history and a positive correlation between age and antemortem tooth loss explain, in part, the reason why humans are more likely to experience tooth loss than non-human primates, but the results do not exclude behavioral differences as a contributing factor. Copyright © 2013 Wiley Periodicals, Inc.

  4. 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 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.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.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.

  5. 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.

  6. The cooperative economy of food: Implications for human life history and physiology.

    Science.gov (United States)

    Kramer, Karen L

    2018-04-06

    The human diet has undergone substantial modifications since the emergence of modern humans and varies considerably in today's traditional societies. Despite these changes and cross-cultural differences, the human diet can be characterized by several common elements. These include diverse, high quality foods, technological complexity to acquire and process food, and the establishment of home bases for storage, processing and consumption. Together these aspects of the human diet challenge any one individual to independently meet all of his or her daily caloric needs. Humans solve this challenge through food sharing, labor exchange and the division of labor. The cooperative nature of the human diet is associated with many downstream effects on our life history and physiology. This paper overviews the constellation of traits that likely led to a cooperative economy of food, and draws on ethnographic examples to illustrate its effects on human life history and physiology. Two detailed examples using body composition, time allocation and food acquisition data show how cooperation among Savanna Pumé hunter-gatherers affects activity levels, sexual dimorphism in body fat, maturational pace and age at first birth. Copyright © 2018. Published by Elsevier Inc.

  7. 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.

  8. 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.

  9. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    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

  11. Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

    Science.gov (United States)

    Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

    2014-01-01

    Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

  12. 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.

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

    Science.gov (United States)

    2017-01-01

    before such systems become part of large-scale operational environments. Effects of emotional response to autonomous systems, ethical software constraints...consolidation and software constructs to represent emotions and temperament to make the robotic agent more accessible to its human teammate (Kelley 2014...agent’s human-like qualities (Rao and Georgeff 1995; Chen and Barnes 2014). Two recent ARL-sponsored projects demonstrate progress toward more- mature

  14. Human impacts on 20th century fire dynamics and implications for global carbon and water trajectories

    Science.gov (United States)

    Li, Fang; Lawrence, David M.; Bond-Lamberty, Ben

    2018-03-01

    Fire is a fundamental Earth system process and the primary ecosystem disturbance on the global scale. It affects carbon and water cycles through changing terrestrial ecosystems, and at the same time, is regulated by weather and climate, vegetation characteristics, and, importantly, human ignitions and suppression (i.e., the direct human effect on fire). Here, we utilize the Community Land Model version 4.5 (CLM4.5) to quantify the impacts of changes in human ignition and suppression on fire dynamics and associated carbon and water cycles. We find that the impact is to significantly reduce the 20th century global burned area by a century average of 38 Mha/yr and by 103 Mha/yr at the end of the century. Land carbon gain is weakened by 17% over the 20th century, mainly due to increased human deforestation fires and associated escape fires (i.e., degradation fires) in the tropical humid forests, even though the decrease in burned area in many other regions due to human fire suppression acts to increase land carbon gain. The direct human effect on fire weakens the upward trend in global runoff throughout the century by 6% and enhances the upward trend in global evapotranspiration since 1945 by 7%. In addition, the above impacts in densely populated, highly developed (if population density > 0.1 person/km2), or moderately populated and developed regions are of opposite sign to those in other regions. Our study suggests that particular attention should be paid to human deforestation and degradation fires in the tropical humid forests when reconstructing and projecting fire carbon emissions and net atmosphere-land carbon exchange and estimating resultant impacts of direct human effect on fire.

  15. 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

  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

    2010-07-01

    Full Text Available 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.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.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.Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions.Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.

  17. Human impacts on 20th century fire dynamics and implications for global carbon and water trajectories

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fang; Lawrence, David M.; Bond-Lamberty, Ben

    2018-03-01

    Fire is a fundamental Earth system process and the primary ecosystem disturbance on the global scale. It affects carbon and water cycles through changing terrestrial ecosystems, and at the same time, is regulated by weather and climate, vegetation characteristics, and, importantly, human ignitions and suppression (i.e., the direct human effect on fire). Here, we utilize the Community Land Model version 4.5 (CLM4.5) to quantify the impacts of changes in human ignition and suppression on fire dynamics and associated carbon and water cycles. We find that the impact is to significantly reduce the 20th century global burned area by a century average of 38 Mha/yr and by 103 Mha/yr at the end of the century. Land carbon gain is weakened by 17% over the 20th century, mainly due to increased human deforestation fires and associated escape fires (i.e., degradation fires) in the tropical humid forests, even though the decrease in burned area in many other regions due to human fire suppression acts to increase land carbon gain. The direct human effect on fire weakens the upward trend in global runoff throughout the century by 6% and enhances the upward trend in global evapotranspiration since ~ 1945 by 7%. In addition, the above impacts in densely populated, highly developed (if population density > 0.1 person/km2), or moderately populated and developed regions are of opposite sign to those in other regions. Our study suggests that particular attention should be paid to human deforestation and degradation fires in the tropical humid forests when reconstructing and projecting fire carbon emissions and net atmosphere-land carbon exchange and estimating resultant impacts of direct human effect on fire.

  18. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 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.

  20. Physical interface dynamics alter how robotic exosuits augment human movement: implications for optimizing wearable assistive devices.

    Science.gov (United States)

    Yandell, Matthew B; Quinlivan, Brendan T; Popov, Dmitry; Walsh, Conor; Zelik, Karl E

    2017-05-18

    Wearable assistive devices have demonstrated the potential to improve mobility outcomes for individuals with disabilities, and to augment healthy human performance; however, these benefits depend on how effectively power is transmitted from the device to the human user. Quantifying and understanding this power transmission is challenging due to complex human-device interface dynamics that occur as biological tissues and physical interface materials deform and displace under load, absorbing and returning power. Here we introduce a new methodology for quickly estimating interface power dynamics during movement tasks using common motion capture and force measurements, and then apply this method to quantify how a soft robotic ankle exosuit interacts with and transfers power to the human body during walking. We partition exosuit end-effector power (i.e., power output from the device) into power that augments ankle plantarflexion (termed augmentation power) vs. power that goes into deformation and motion of interface materials and underlying soft tissues (termed interface power). We provide empirical evidence of how human-exosuit interfaces absorb and return energy, reshaping exosuit-to-human power flow and resulting in three key consequences: (i) During exosuit loading (as applied forces increased), about 55% of exosuit end-effector power was absorbed into the interfaces. (ii) However, during subsequent exosuit unloading (as applied forces decreased) most of the absorbed interface power was returned viscoelastically. Consequently, the majority (about 75%) of exosuit end-effector work over each stride contributed to augmenting ankle plantarflexion. (iii) Ankle augmentation power (and work) was delayed relative to exosuit end-effector power, due to these interface energy absorption and return dynamics. Our findings elucidate the complexities of human-exosuit interface dynamics during transmission of power from assistive devices to the human body, and provide insight into

  1. A human rights approach to the health implications of food and nutrition insecurity.

    Science.gov (United States)

    Ayala, Ana; Meier, Benjamin Mason

    2017-01-01

    Food and nutrition insecurity continues to pose a serious global challenge, reflecting government shortcomings in meeting international obligations to ensure the availability, accessibility, and quality of food and to ensure the highest attainable standard of health of their peoples. With global drivers like climate change, urbanization, greater armed conflict, and the globalization of unhealthy diet, particularly in under-resourced countries, food insecurity is rapidly becoming an even greater challenge for those living in poverty. International human rights law can serve a critical role in guiding governments that are struggling to protect the health of their populations, particularly among the most susceptible groups, in responding to food and nutrition insecurity. This article explores and advocates for a human rights approach to food and nutrition security, specifically identifying legal mechanisms to "domesticate" relevant international human rights standards through national policy. Recognizing nutrition security as a determinant of public health, this article recognizes the important links between the four main elements of food security (i.e., availability, stability, utilization, and access) and the normative attributes of the right to health and the right to food (i.e., availability, accessibility, affordability, and quality). In drawing from the evolution of international human rights instruments, official documents issued by international human rights treaty bodies, as well as past scholarship at the intersection of the right to health and right to food, this article interprets and articulates the intersectional rights-based obligations of national governments in the face of food and nutrition insecurity.

  2. Organochlorines in urban soils from Central India: probabilistic health hazard and risk implications to human population.

    Science.gov (United States)

    Kumar, Bhupander; Mishra, Meenu; Verma, V K; Rai, Premanjali; Kumar, Sanjay

    2018-04-21

    This study presents distribution of organochlorines (OCs) including HCH, DDT and PCBs in urban soils, and their environmental and human health risk. Forty-eight soil samples were extracted using ultrasonication, cleaned with modified silica gel chromatography and analyzed by GC-ECD. The observed concentrations of ∑HCH, ∑DDT and ∑PCBs in soils ranged between < 0.01-2.54, 1.30-27.41 and < 0.01-62.8 µg kg -1 , respectively, which were lower than the recommended soil quality guidelines. Human health risk was estimated following recommended guidelines. Lifetime average daily dose (LADD), non-cancer risk or hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) for humans due to individual and total OCs were estimated and presented. Estimated LADD were lower than acceptable daily intake and reference dose. Human health risk estimates were lower than safe limit of non-cancer risk (HQ < 1.0) and the acceptable distribution range of ILCR (10 -6 -10 -4 ). Therefore, this study concluded that present levels of OCs (HCH, DDT and PCBs) in studied soils were low, and subsequently posed low health risk to human population in the study area.

  3. 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.

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

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.

  5. 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

  6. "Pollical palmar interosseous muscle" (musculus adductor pollicis accessorius): attachments, innervation, variations, phylogeny, and implications for human evolution and medicine.

    Science.gov (United States)

    Bello-Hellegouarch, Gaelle; Aziz, M Ashraf; Ferrero, Eva M; Kern, Michael; Francis, Nadia; Diogo, Rui

    2013-03-01

    Most atlases and textbooks dealing with human anatomy do not refer to the "pollical palmar interosseous" (PPI) muscle of Henle. In order to undertake a fresh and detailed study of this muscle and to thus better understand human comparative anatomy and evolution, we: 1) analyze the frequency of the PPI in a large sample of human hands; 2) describe the attachments, innervation and varieties of the PPI in these hands; 3) compare the data obtained with the information available in the literature; and 4) discuss the phylogenetic origin of the PPI and the implications of our observations and comparisons for medicine and for the understanding of human evolutionary history. Within the 72 hands dissected by us, the PPI is present in 67 hands (93%), commonly having a single muscular branch, originating from the medial side of the base of metacarpal I only, inserting onto the medial side of the base of the pollical proximal phalanx and/or surrounding structures (e.g., ulnar sesamoid bone, wing tendon of extensor apparatus), and passing at least partially, and usually mainly, medial to the princeps pollicis artery. A careful study of the human PPI, as well as a detailed comparison with other mammals, strongly suggest that the muscle is evolutionarily derived from the adductor pollicis, and namely from its oblique head. Therefore, we propose that PPI should be designated by the name musculus adductor pollicis accessorius, which indicates that the muscle is most likely a de novo structure derived from the adductor pollicis. Copyright © 2012 Wiley Periodicals, Inc.

  7. 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

  8. Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence.

    Science.gov (United States)

    Heim, Cortney E; Vidlak, Debbie; Odvody, Jessica; Hartman, Curtis W; Garvin, Kevin L; Kielian, Tammy

    2017-11-15

    Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33 + HLA-DR - CD66b + CD14 -/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. 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.

  10. Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.

    Science.gov (United States)

    Kuper, C Frieke; van Bilsen, Jolanda; Cnossen, Hilde; Houben, Geert; Garthoff, Jossie; Wolterbeek, Andre

    2016-09-01

    A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M.

    1990-01-01

    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

  12. 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.

  13. 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.

  14. 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.

  15. Chloroform and trichloroethylene uptake from water into human skin in vitro: Kinetics and risk implications

    International Nuclear Information System (INIS)

    Bogen, K.T.; Keating, G.A.; Vogel, J.S.

    1995-03-01

    A model recently proposed by the US Environmental Protection Agency (EPA) predicts that short-term dermal uptakes of organic environmental water contaminants are proportional to the square root of exposure time. The model appears to underestimate dermal uptake, based on very limited in vivo uptake data obtained primarily using human subjects. To further assess this model, we examined in vitro dermal uptake kinetics for aqueous organic chemicals using accelerator mass spectrometry (AMS). Specifically, we examined the kinetics of in vitro dermal uptake of 14 C-labeled chloroform and trichloroethylene from dilute (5-ppb) aqueous solutions using full-thickness human cadaver skin exposed for (≤1 hr)

  16. Digital companion species and eating data: Implications for theorising digital data–human assemblages

    Directory of Open Access Journals (Sweden)

    Deborah Lupton

    2016-01-01

    Full Text Available This commentary is an attempt to begin to identify and think through some of the ways in which sociocultural theory may contribute to understandings of the relationship between humans and digital data. I develop an argument that rests largely on the work of two scholars in the field of science and technology studies: Donna Haraway and Annemarie Mol. Both authors emphasised materiality and multiple ontologies in their writing. I argue that these concepts have much to offer critical data studies. I employ the tropes of companion species, drawn from Haraway, and eating data, from Mol, and demonstrate how these may be employed to theorise digital data–human assemblages.

  17. 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

  18. Entrainment of the circadian clock in humans: mechanism and implications for sleep disorders.

    Directory of Open Access Journals (Sweden)

    David Metcalfe

    2007-01-01

    Full Text Available Humans exhibit behaviour and physiology controlled by a circadian clock. The circadian period is genetically determined and administered by a series of interlocked autoregulatory feedback loops largely in the suprachiasmatic nuclei of the hypothalamus. The phase of the clock is, however, synchronised by a number of external environmental cues such as light. A failure or change in any one of the requisite clock components may result in the onset of a long-term sleep disorder. This review discusses the mechanism regulating circadian physiology in humans and explores how disturbances of this mechanism may result in sleep pathologies.

  19. 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...

  20. Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology

    Science.gov (United States)

    Wang, Xiaoxia; Chow, Renee; Deng, Liwen; Anderson, Dan; Weidner, Noel; Godwin, Andrew K; Bewtra, Chanda; Zlotnik, Albert; Bui, Jack; Varki, Ajit; Varki, Nissi

    2011-01-01

    Siglecs (Sialic acid-binding Immunoglobulin Superfamily Lectins) are cell surface signaling receptors of the I-type lectin group that recognize sialic acid-bearing glycans. CD33-related-Siglecs are a subset with expression primarily in cells of hematopoietic origin and functional relevance to immune reactions. Earlier we reported a human-specific gene conversion event that markedly changed the coding region for the extracellular domain of Siglec-11, associated with human-specific expression in microglia (Hayakawa T, Angata T, Lewis AL, Mikkelsen TS, Varki NM, Varki A. 2005. A human-specific gene in microglia. Science. 309:1693). Analyzing human gene microarrays to define new patterns of expression, we observed high levels of SIGLEC11 transcript in the ovary and adrenal cortex. Thus, we examined human and chimpanzee tissues using a well-characterized anti-Siglec-11 mouse monoclonal antibody. Although adrenal expression was variable and confined to infiltrating macrophages in capillaries, ovarian expression of Siglec-11 in both humans and chimpanzees was on fibroblasts, the first example of Siglec expression on mesenchyme-derived stromal cells. Cytokines from such ovarian stromal fibroblasts play important roles in follicle development and ovulation. Stable transfection of SIGLEC11 into a primary human ovarian stromal fibroblast cell line altered the secretion of growth-regulated oncogene α, interleukin (IL)-10, IL-7, transforming growth factor β1 and tumor necrosis factor-α, cytokines involved in ovarian physiology. Probing for Siglec-11 ligands revealed distinct and strong mast cell expression in human ovaries, contrasting to diffuse stromal ligands in chimpanzee ovaries. Interestingly, there was a trend of increased Siglec-11 expression in post-menopausal ovaries compared with pre-menopausal ones. Siglec-11 expression was also found on human ovarian stromal tumors and in polycystic ovarian syndrome, a human-specific disease. These results indicate potential

  1. 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.

  2. Lens oscillations in the human eye. Implications for post-saccadic suppression of vision.

    Directory of Open Access Journals (Sweden)

    Juan Tabernero

    Full Text Available The eye changes gaze continuously from one visual stimulus to another. Using a high speed camera to record eye and lens movements we demonstrate how the crystalline lens sustains an inertial oscillatory decay movement immediately after every change of gaze. This behavior fit precisely with the movement of a classical damped harmonic oscillator. The time course of the oscillations range from 50 to 60 msec with an oscillation frequency of around 20 Hz. That has dramatic implications on the image quality at the retina on the very short times (∼50 msec that follow the movement. However, it is well known that our vision is nearly suppressed on those periods (post-saccadic suppression. Both phenomenon follow similar time courses and therefore might be synchronized to avoid the visual impairment.

  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. Meiotic and post-meiotic studies in the male mouse exposed to X-rays and their human implications

    International Nuclear Information System (INIS)

    Szemere, G.

    1977-01-01

    Cytological studies were carried out on the meiotic process of control and irradiated male mice in order to provide direct means of estimating the non-disjunction rate for autosomes and sex chromosomes. Analysis of second meiotic divisions showed that while spontaneous rates of anaphase I non-disjunctions were extremely low, they could be enhanced by X-ray treatment of prophase spermatocytes. Irradiation at pre-leptotene resulted in a higher rate of anaphase I non-disjunction than did irradiation at pachytene, while early spermatogonia were relatively insensitive. In the present experiments, a relatively high proportion of chromosomally abnormal fetuses (including triploidy, X monosomy, autosomal trisomy and several mosaicisms) have been found amoung the progeny of males irradiated at pre-leptotene. The human implications of these findings with respect to the radiation hazards are discussed

  5. Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications

    Directory of Open Access Journals (Sweden)

    Jung Eun Lee

    2017-03-01

    Full Text Available Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life.

  6. Implications for the human food chain of models of cadmium accumulation in sheep

    International Nuclear Information System (INIS)

    Prankel, S.H.; Nixon, R.M.; Phillips, C.J.C.

    2005-01-01

    Critical limits for cadmium in parts of the human food chain are considered to have too small margins of safety and some limits are regularly exceeded. There is concern about the exposure of some sections of the population to cadmium in the human food chain, in particular regarding offal, which is a major source of cadmium to some sectors. The kidney is the first organ of sheep to reach the limit of fitness for human consumption. A model (based on a meta-analysis) predicts that this would occur after a mean of just 130 days of feeding sheep the maximum permitted cadmium concentration in feed (in the European Union) in the organic form. Thus it is not surprising that sheep organs are found routinely to exceed cadmium limits. Since reduction of maximum cadmium levels in sheep feed or of the duration of their exposure are not economically viable measures of control, routine removal of liver and kidney from older sheep from the food chain is recommended as the best option to reduce human dietary cadmium intake from sheep origin

  7. Microsporidian species known to infect humans are present in aquatic birds: implications for transmission via water?

    Science.gov (United States)

    Slodkowicz-Kowalska, Anna; Graczyk, Thaddeus K; Tamang, Leena; Jedrzejewski, Szymon; Nowosad, Andrzej; Zduniak, Piotr; Solarczyk, Piotr; Girouard, Autumn S; Majewska, Anna C

    2006-07-01

    Human microsporidiosis, a serious disease of immunocompetent and immunosuppressed people, can be due to zoonotic and environmental transmission of microsporidian spores. A survey utilizing conventional and molecular techniques for examining feces from 570 free-ranging, captive, and livestock birds demonstrated that 21 animals shed microsporidian spores of species known to infect humans, including Encephalitozoon hellem (20 birds; 3.5%) and Encephalitozoon intestinalis (1 bird; 0.2%). Of 11 avian species that shed E. hellem and E. intestinalis, 8 were aquatic birds (i.e., common waterfowl). The prevalence of microsporidian infections in waterfowl (8.6%) was significantly higher than the prevalence of microsporidian infections in other birds (1.1%) (P < 0.03); waterfowl fecal droppings contained significantly more spores (mean, 3.6 x 10(5) spores/g) than nonaquatic bird droppings contained (mean, 4.4 x 10(4) spores/g) (P < 0.003); and the presence of microsporidian spores of species known to infect humans in fecal samples was statistically associated with the aquatic status of the avian host (P < 0.001). We demonstrated that a single visit of a waterfowl flock can introduce into the surface water approximately 9.1 x 10(8) microsporidian spores of species known to infect humans. Our findings demonstrate that waterborne microsporidian spores of species that infect people can originate from common waterfowl, which usually occur in large numbers and have unlimited access to surface waters, including waters used for production of drinking water.

  8. Do humans still forage in an obesogenic environment? Mechanisms and implications for weight maintenance.

    Science.gov (United States)

    Brunstrom, Jeffrey M; Cheon, Bobby K

    2018-02-19

    Many people struggle to control their food intake and bodyweight. This is often interpreted as evidence that humans are generally predisposed to consume food when it is available, because adiposity offered insurance against the threat of starvation in our ancestral environment. In this paper we suggest that modern humans have actually inherited a far broader range of foraging skills that continue to influence our dietary behaviour. To evaluate this idea, we identify three challenges that would need to be addressed to achieve efficient foraging; (1) monitoring the 'procurement cost' of foods, (2) determining the energy content of foods, and (3) proactively adapting to perceived food insecurity. In each case, we review evidence drawn from controlled and observational studies of contemporary humans and conclude that psychological mechanisms that address these challenges are conserved. For contemporary humans who live in fast-paced obesogenic environments, this foraging 'toolkit' no longer serves the same function to which it was adapted, and in many cases, this leads to an increase in food intake. Understanding these forms of 'evolutionary mismatch' is important because it can provide a stronger theoretical basis for informed dietary interventions that leverage fundamental foraging goals rather than work against them. Copyright © 2018. Published by Elsevier Inc.

  9. Humans are parochial altruists: neurocognitive foundations with implications for intergroup negotiation

    NARCIS (Netherlands)

    de Dreu, C.K.W.; Martinovski, B.

    2013-01-01

    Humans have a stunning capacity for cooperation yet, at the same time, create and escalate conflict with often devastating consequences. Here I argue that both tendencies -- to cooperate and to aggress -- can be understood as manifestations of parochial altruism--the tendency to benefit, at a cost

  10. Detection of titanium particles in human liver and spleen and possible health implications

    NARCIS (Netherlands)

    Heringa, M.B.; Peters, R.J.B.; Bleys, R.L.A.W.; Lee, van der M.K.; Tromp, P.C.; Kesteren, van P.C.E.; Eijkeren, van J.C.H.; Undas, A.K.; Oomen, A.G.; Bouwmeester, H.

    2018-01-01

    Background: Titanium dioxide (TiO2) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO2 to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal

  11. 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

  12. Convex hull and tour crossings in the Euclidean traveling salesperson problem : implications for human performance studies

    NARCIS (Netherlands)

    Rooij, van I.; Stege, U.; Schactman, A.

    2003-01-01

    Recently there has been growing interest among psychologists in human performance on the Euclidean traveling salesperson problem (E-TSP). A debate has been initiated on what strategy people use in solving visually presented E-TSP instances. The most prominent hypothesis is the convex-hull

  13. 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…

  14. 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…

  15. Characterization of Common Measures of Heart Period Variability in Healthy Human Subjects: Implications for Patient Monitoring

    Science.gov (United States)

    2010-01-01

    sports medicine and science. Sports Med 2000; 30: 1–15. 41. Eckberg DL. The human respiratory gate. J Physiol 2003; 548: 339–352. 42. Kamen PW, Krum H...in short-term HRV analysis. Biomed Tech 2006; 51: 190–193. 45. Hayano J, Taylor JA, Yamada A, et al. Continuous assessment of hemodynamic control by

  16. Neuromandibular integration in humans and chimpanzees: Implications for dental and mandibular reduction in Homo.

    Science.gov (United States)

    Veneziano, Alessio; Meloro, Carlo; Irish, Joel D; Stringer, Chris; Profico, Antonio; De Groote, Isabelle

    2018-05-08

    Although the evolution of the hominin masticatory apparatus has been linked to diet and food processing, the physical connection between neurocranium and lower jaw suggests a role of encephalization in the trend of dental and mandibular reduction. Here, the hypothesis that tooth size and mandibular robusticity are influenced by morphological changes in the neurocranium was tested. Three-dimensional landmarks, alveolar lengths, and mandibular robusticity data were recorded on a sample of chimpanzee and human skulls. The morphological integration between the neurocranium and the lower jaw was analyzed by means of Singular Warps Analysis. Redundancy Analysis was performed to understand if the pattern of neuromandibular integration affects tooth size and mandibular robusticity. There is significant morphological covariation between neurocranium and lower jaw in both chimpanzees and humans. In humans, changes in the temporal fossa seem to produce alterations of the relative orientation of jaw parts, while the influence of similar neurocranial changes in chimpanzees are more localized. In both species, postcanine alveolar lengths and mandibular robusticity are associated with shape changes of the temporal fossa. The results of this study support the hypothesis that the neurocranium is able to affect the evolution and development of the lower jaw, although most likely through functional integration of mandible, teeth, and muscles within the masticatory apparatus. This study highlights the relative influence of structural constraints and adaptive factors in the evolution of the human skull. © 2018 Wiley Periodicals, Inc.

  17. Metabolic changes during treatment with valproate in humans: Implication for untoward weight gain

    DEFF Research Database (Denmark)

    Breum, L.; Astrup, A.; Gram, L.

    1992-01-01

    of carnitine in humans, it is hypothesized that a possible VPA-induced deficiency of the beta-oxidation of fatty acids is important for the development of obesity in epileptic patients in long-term treatment with VPA, but changes in catecholamines or other hormones might also be of importance....

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

    Czech Academy of Sciences Publication Activity Database

    Benazzi, S.; Douka, K.; Fornai, C.; Bauer, C. C.; Kullmer, O.; Svoboda, Jiří; Pap, I.; Mallegni, F.; Bayle, P.; Coquerelle, M.; Condemi, S.; Ronchitelli, A.; Harvati, K.; Weber, G. W.

    2011-01-01

    Roč. 479, č. 7374 (2011), s. 525-528 ISSN 0028-0836 Institutional research plan: CEZ:AV0Z80010507 Keywords : modern humans * Neanderthals * behavior * Europe * Grotta del Cavallo * paleoanthropology Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 36.280, year: 2011

  19. 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...

  20. The serotonergic anatomy of the developing human medulla oblongata: implications for pediatric disorders of homeostasis.

    Science.gov (United States)

    Kinney, Hannah C; Broadbelt, Kevin G; Haynes, Robin L; Rognum, Ingvar J; Paterson, David S

    2011-07-01

    The caudal serotonergic (5-HT) system is a critical component of a medullary "homeostatic network" that regulates protective responses to metabolic stressors such as hypoxia, hypercapnia, and hyperthermia. We define anatomically the caudal 5-HT system in the human medulla as 5-HT neuronal cell bodies located in the raphé (raphé obscurus, raphé magnus, and raphé pallidus), extra-raphé (gigantocellularis, paragigantocellularis lateralis, intermediate reticular zone, lateral reticular nucleus, and nucleus subtrigeminalis), and ventral surface (arcuate nucleus). These 5-HT neurons are adjacent to all of the respiratory- and autonomic-related nuclei in the medulla where they are positioned to modulate directly the responses of these effector nuclei. In the following review, we highlight the topography and development of the caudal 5-HT system in the human fetus and infant, and its inter-relationships with nicotinic, GABAergic, and cytokine receptors. We also summarize pediatric disorders in early life which we term "developmental serotonopathies" of the caudal (as well as rostral) 5-HT domain and which are associated with homeostatic imbalances. The delineation of the development and organization of the human caudal 5-HT system provides the critical foundation for the neuropathologic elucidation of its disorders directly in the human brain. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Economy-Wide estimates of the implications of climate change: Human health

    NARCIS (Netherlands)

    Bosello, F.; Roson, R.; Tol, R.S.J.

    2006-01-01

    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

  2. The pastoral implications of human freedom according to Juan Luis Segundo

    Directory of Open Access Journals (Sweden)

    Vicente de Paula Ferreira

    2016-09-01

    Full Text Available The paper aims to reflect the issue of human freedom based on the underlying principles of the Christian faith in a time of anthropological vulnerability, especially in Latin American. It holds that Christianity must insist on its proposal to promote universal goodwill, despite a human horizon marked by selfishness and lust for power and money. This approach presupposes a radical position of a listener of the divine mystery, revealed in Jesus Christ, as a way to fulfill the human condition. Theoretical framework: Liberation Theology, in the view of Juan Luis Segundo, and its well-established tradition of transforming realities of injustice through faith, comprises the core argument of this text. Findings: Christian salvation necessarily implies the kenosis (κένωσις of Jesus, i.e., Christ “emptied Himself” (Ph. 2:7, and through His humble dispossession, He broke with all closed systems of the world, and inaugurated a new venture of a liberated freedom: the agape of love. Conclusion: Christian praxis as daily care for the poorest and prophecy of forgiveness rescues the memory of the victims of all forms of human selfishness. 

  3. Form and function of the human and chimpanzee forefoot: implications for early hominin bipedalism

    Science.gov (United States)

    Fernández, Peter J.; Holowka, Nicholas B.; Demes, Brigitte; Jungers, William L.

    2016-01-01

    During bipedal walking, modern humans dorsiflex their forefoot at the metatarsophalangeal joints (MTPJs) prior to push off, which tightens the plantar soft tissues to convert the foot into a stiff propulsive lever. Particular features of metatarsal head morphology such as “dorsal doming” are thought to facilitate this stiffening mechanism. In contrast, chimpanzees are believed to possess MTPJ morphology that precludes high dorsiflexion excursions during terrestrial locomotion. The morphological affinity of the metatarsal heads has been used to reconstruct locomotor behavior in fossil hominins, but few studies have provided detailed empirical data to validate the assumed link between morphology and function at the MTPJs. Using three-dimensional kinematic and morphometric analyses, we show that humans push off with greater peak dorsiflexion angles at all MTPJs than do chimpanzees during bipedal and quadrupedal walking, with the greatest disparity occurring at MTPJ 1. Among MTPJs 2–5, both species exhibit decreasing peak angles from medial to lateral. This kinematic pattern is mirrored in the morphometric analyses of metatarsal head shape. Analyses of Australopithecus afarensis metatarsals reveal morphology intermediate between humans and chimpanzees, suggesting that this species used different bipedal push-off kinematics than modern humans, perhaps resulting in a less efficient form of bipedalism. PMID:27464580

  4. From Mendel to the Human Genome Project: The Implications for Nurse Education.

    Science.gov (United States)

    Burton, Hilary; Stewart, Alison

    2003-01-01

    The Human Genome Project is brining new opportunities to predict and prevent diseases. Although pediatric nurses are the closest to these developments, most nurses will encounter genetic aspects of practice and must understand the basic science and its ethical, legal, and social dimensions. (Includes commentary by Peter Birchenall.) (SK)

  5. 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. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  6. Poverty as human rights deficit : some implications for the international financial institutions

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2003-01-01

    Following the World Bank’s World Development Report2000/2001: The attack on poverty and the voices of the poor studies on which that document had been based, this chapter explores Human Rights obligations of the International Financial Institutions (IFIs). In this connection poverty is approached as

  7. 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-lim...

  8. 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.

  9. 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.

  10. High activity of fatty acid oxidation enzymes in human placenta: implications for fetal-maternal disease

    NARCIS (Netherlands)

    Oey, N. A.; den Boer, M. E. J.; Ruiter, J. P. N.; Wanders, R. J. A.; Duran, M.; Waterham, H. R.; Boer, K.; van der Post, J. A. M.; Wijburg, F. A.

    2003-01-01

    As the human fetus and placenta are considered to be primarily dependent on glucose oxidation for energy metabolism, the cause of the remarkable association between severe maternal pregnancy complications and the carriage of a fetus with an inborn error of mitochondrial long-chain fatty acid

  11. 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

  12. Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc.

    Science.gov (United States)

    Le Maitre, Christine L; Richardson, Stephen M A; Baird, Pauline; Freemont, Anthony J; Hoyland, Judith A

    2005-12-01

    Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic

  13. Mercury contamination in fish and human hair from Hainan Island, South China Sea: Implication for human exposure.

    Science.gov (United States)

    Liu, Jin-Ling; Xu, Xiang-Rong; Yu, Shen; Cheng, Hefa; Peng, Jia-Xi; Hong, Yi-Guo; Feng, Xin-Bin

    2014-11-01

    Hair has long been recognized as a good biomarker for human exposure to Hg. The mercury concentrations in 14 species of marine fish and hair samples from 177 coastal residents in Hainan, South China Sea were investigated to assess the status of mercury exposure associated with marine fish consumption. Concentrations of total Hg (THg) and methylmercury (MeHg) in the fish muscles were 0.094 ± 0.008 and 0.066 ± 0.006 μg/gww, respectively, which were far below the limit considered safe for consumption (0.5 μg/g). The average THg concentrations in hair of adults (1.02 ± 0.92 μg/g) were lower than the provisional tolerable weekly intake (PTWI) level of 2.2 μg/g. However, 23.7% of children had a hair THg level exceeding the RfD level of 1μg/g, indicating a great risk of Hg exposure to children via fish consumption. The concentration of THg in hair was significantly correlated with fish consumption but not with gender-specific fish intake. With higher fish consumption frequency, the fishermen had significantly elevated hair Hg levels compared to the students and the other general public, who had similar hair THg levels but different fish consumption patterns, indicating the existence of other sources of Hg exposure to the residents of Hainan Island. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Calcaneus length determines running economy: implications for endurance running performance in modern humans and Neandertals.

    Science.gov (United States)

    Raichlen, David A; Armstrong, Hunter; Lieberman, Daniel E

    2011-03-01

    The endurance running (ER) hypothesis suggests that distance running played an important role in the evolution of the genus Homo. Most researchers have focused on ER performance in modern humans, or on reconstructing ER performance in Homo erectus, however, few studies have examined ER capabilities in other members of the genus Homo. Here, we examine skeletal correlates of ER performance in modern humans in order to evaluate the energetics of running in Neandertals and early Homo sapiens. Recent research suggests that running economy (the energy cost of running at a given speed) is strongly related to the length of the Achilles tendon moment arm. Shorter moment arms allow for greater storage and release of elastic strain energy, reducing energy costs. Here, we show that a skeletal correlate of Achilles tendon moment arm length, the length of the calcaneal tuber, does not correlate with walking economy, but correlates significantly with running economy and explains a high proportion of the variance (80%) in cost between individuals. Neandertals had relatively longer calcaneal tubers than modern humans, which would have increased their energy costs of running. Calcaneal tuber lengths in early H. sapiens do not significantly differ from those of extant modern humans, suggesting Neandertal ER economy was reduced relative to contemporaneous anatomically modern humans. Endurance running is generally thought to be beneficial for gaining access to meat in hot environments, where hominins could have used pursuit hunting to run prey taxa into hyperthermia. We hypothesize that ER performance may have been reduced in Neandertals because they lived in cold climates. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Solution structure of human intestinal fatty acid binding protein: Implications for ligand entry and exit

    International Nuclear Information System (INIS)

    Zhang Fengli; Luecke, Christian; Baier, Leslie J.; Sacchettini, James C.; Hamilton, James A.

    1997-01-01

    The human intestinal fatty acid binding protein (I-FABP) is a small (131 amino acids) protein which binds dietary long-chain fatty acids in the cytosol of enterocytes. Recently, an alanine to threonine substitution at position 54 in I-FABP has been identified which affects fatty acid binding and transport, and is associated with the development of insulin resistance in several populations including Mexican-Americans and Pima Indians. To investigate the molecular basis of the binding properties of I-FABP, the 3D solution structure of the more common form of human I-FABP (Ala54) was studied by multidimensional NMR spectroscopy.Recombinant I-FABP was expressed from E. coli in the presence and absence of 15N-enriched media. The sequential assignments for non-delipidated I-FABP were completed by using 2D homonuclear spectra (COSY, TOCSY and NOESY) and 3D heteronuclear spectra(NOESY-HMQC and TOCSY-HMQC). The tertiary structure of human I-FABP was calculated by using the distance geometry program DIANA based on 2519 distance constraints obtained from the NMR data. Subsequent energy minimization was carried out by using the program SYBYL in the presence of distance constraints. The conformation of human I-FABP consists of 10 antiparallel β-strands which form two nearly orthogonal β-sheets of five strands each, and two short α-helices that connect the β-strands A and B. The interior of the protein consists of a water-filled cavity between the two β-sheets. The NMR solution structure of human I-FABP is similar to the crystal structure of rat I-FABP.The NMR results show significant conformational variability of certain backbone segments around the postulated portal region for the entry and exit of fatty acid ligand

  16. Solution structure of human intestinal fatty acid binding protein: Implications for ligand entry and exit

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Fengli [Boston University School of Medicine, Department of Biophysics (United States); Luecke, Christian [Johann Wolfgang Goethe-Universitaet (Germany); Baier, Leslie J. [NIDDK, NIH, Phoenix Epidemiology and Clinical Research Branch (United States); Sacchettini, James C. [Texas A and M University, Department of Biochemistry and Biophysics (United States); Hamilton, James A. [Boston University School of Medicine, Department of Biophysics (United States)

    1997-04-15

    The human intestinal fatty acid binding protein (I-FABP) is a small (131 amino acids) protein which binds dietary long-chain fatty acids in the cytosol of enterocytes. Recently, an alanine to threonine substitution at position 54 in I-FABP has been identified which affects fatty acid binding and transport, and is associated with the development of insulin resistance in several populations including Mexican-Americans and Pima Indians. To investigate the molecular basis of the binding properties of I-FABP, the 3D solution structure of the more common form of human I-FABP (Ala54) was studied by multidimensional NMR spectroscopy.Recombinant I-FABP was expressed from E. coli in the presence and absence of 15N-enriched media. The sequential assignments for non-delipidated I-FABP were completed by using 2D homonuclear spectra (COSY, TOCSY and NOESY) and 3D heteronuclear spectra(NOESY-HMQC and TOCSY-HMQC). The tertiary structure of human I-FABP was calculated by using the distance geometry program DIANA based on 2519 distance constraints obtained from the NMR data. Subsequent energy minimization was carried out by using the program SYBYL in the presence of distance constraints. The conformation of human I-FABP consists of 10 antiparallel {beta}-strands which form two nearly orthogonal {beta}-sheets of five strands each, and two short {alpha}-helices that connect the {beta}-strands A and B. The interior of the protein consists of a water-filled cavity between the two {beta}-sheets. The NMR solution structure of human I-FABP is similar to the crystal structure of rat I-FABP.The NMR results show significant conformational variability of certain backbone segments around the postulated portal region for the entry and exit of fatty acid ligand.

  17. Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders

    Directory of Open Access Journals (Sweden)

    Liang Xu

    2017-09-01

    Full Text Available Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26, a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity.Methods: By screening a combinatorial library of human single-chain fragment variable (scFv antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells.Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action

  18. Molecular Epidemiology of Nontyphoidal Salmonella in Poultry and Poultry Products in India: Implications for Human Health.

    Science.gov (United States)

    Saravanan, Sellappan; Purushothaman, Venketaraman; Murthy, Thippichettypalayam Ramasamy Gopala Krishna; Sukumar, Kuppannan; Srinivasan, Palani; Gowthaman, Vasudevan; Balusamy, Mohan; Atterbury, Robert; Kuchipudi, Suresh V

    2015-09-01

    Human infections with non-typhoidal Salmonella (NTS) serovars are increasingly becoming a threat to human health globally. While all motile Salmonellae have zoonotic potential, Salmonella Enteritidis and Salmonella Typhimurium are most commonly associated with human disease, for which poultry are a major source. Despite the increasing number of human NTS infections, the epidemiology of NTS in poultry in India has not been fully understood. Hence, as a first step, we carried out epidemiological analysis to establish the incidence of NTS in poultry to evaluate the risk to human health. A total of 1215 samples (including poultry meat, tissues, egg and environmental samples) were collected from 154 commercial layer farms from southern India and screened for NTS. Following identification by cultural and biochemical methods, Salmonella isolates were further characterized by multiplex PCR, allele-specific PCR, enterobacterial repetitive intergenic consensus (ERIC) PCR and pulse field gel electrophoresis (PFGE). In the present study, 21/1215 (1.73 %) samples tested positive for NTS. We found 12/392 (3.06 %) of tissue samples, 7/460 (1.52 %) of poultry products, and 2/363 (0.55 %) of environmental samples tested positive for NTS. All the Salmonella isolates were resistant to oxytetracycline, which is routinely used as poultry feed additive. The multiplex PCR results allowed 16/21 isolates to be classified as S. Typhimurium, and five isolates as S. Enteritidis. Of the five S. Enteritidis isolates, four were identified as group D Salmonella by allele-specific PCR. All of the isolates produced different banding patterns in ERIC PCR. Of the thirteen macro restriction profiles (MRPs) obtained by PFGE, MRP 6 was predominant which included 6 (21 %) isolates. In conclusion, the findings of the study revealed higher incidence of contamination of NTS Salmonella in poultry tissue and animal protein sources used for poultry. The results of the study warrants further investigation

  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. Biomechanics of normal and pathological gait: implications for understanding human locomotor control.

    Science.gov (United States)

    Winter, D A

    1989-12-01

    The biomechanical (kinetic) analysis of human gait reveals the integrated and detailed motor patterns that are essential in pinpointing the abnormal patterns in pathological gait. In a similar manner, these motor patterns (moments, powers, and EMGs) can be used to identify synergies and to validate theories of CNS control. Based on kinetic and EMG patterns for a wide range of normal subjects and cadences, evidence is presented that both supports and negates the central pattern generator theory of locomotion. Adaptive motor patterns that are evident in peripheral gait pathologies reinforce a strong peripheral rather than a central control. Finally, a three-component subtask theory of human gait is presented and is supported by reference to the motor patterns seen in a normal gait. The identified subtasks are (a) support (against collapse during stance); (b) dynamic balance of the upper body, also during stance; and (c) feedforward control of the foot trajectory to achieve safe ground clearance and a gentle heel contact.

  1. Receptors for sensory neuropeptides in human inflammatory diseases: Implications for the effector role of sensory neurons

    International Nuclear Information System (INIS)

    Mantyh, P.W.; Catton, M.D.; Boehmer, C.G.; Welton, M.L.; Passaro, E.P. Jr.; Maggio, J.E.; Vigna, S.R.

    1989-01-01

    Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues

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

    International Nuclear Information System (INIS)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Kerr, Iain D.; Min, Jinrong

    2015-01-01

    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

  3. 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.

  4. The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive.

    Science.gov (United States)

    Goldman-Rakic, P S

    1996-10-29

    The functional architecture of prefrontal cortex is central to our understanding of human mentation and cognitive prowess. This region of the brain is often treated as an undifferentiated structure, on the one hand, or as a mosaic of psychological faculties, on the other. This paper focuses on the working memory processor as a specialization of prefrontal cortex and argues that the different areas within prefrontal cortex represent iterations of this function for different information domains, including spatial cognition, object cognition and additionally, in humans, semantic processing. According to this parallel processing architecture, the 'central executive' could be considered an emergent property of multiple domain-specific processors operating interactively. These processors are specializations of different prefrontal cortical areas, each interconnected both with the domain-relevant long-term storage sites in posterior regions of the cortex and with appropriate output pathways.

  5. 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.

  6. Cyanobacteria, neurotoxins and water resources: are there implications for human neurodegenerative disease?

    Science.gov (United States)

    Metcalf, James S; Codd, Geoffrey A

    2009-01-01

    Cyanobacteria are cosmopolitan microbes that inhabit marine, freshwater and terrestrial environments. Under favourable conditions in waterbodies, they can form massive populations (blooms and scums), which present hazards to human and animal health. Such cyanobacteria often contain a variety of toxic substances (cyanotoxins) that can exist as both cell-associated and free forms in the surrounding water. Some cyanotoxins are highly neurotoxic and act through a variety of mechanisms. Recent findings of the production of the neurotoxin beta-N-methylamino-L-alanine (BMAA) by cyanobacteria in aquatic environments, and of BMAA in brain and cerebrospinal fluid samples of amyotrophic lateral sclerosis and Alzheimer's disease victims, raises the possibility that people may be exposed to waterborne BMAA of cyanobacterial origin and that this may contribute to human neurodegenerative disease. An understanding of the risks presented by waterborne BMAA and of available mitigation strategies to reduce this potential exposure is needed.

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

    International Nuclear Information System (INIS)

    Chevalier, G.; Chevalier, G.; Sinatra, S.T.; Oschman, J.L.; Sokal, K.; Sokal, P.

    2012-01-01

    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 un wellness. 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

  8. Human health implications of organic food and organic agriculture: a comprehensive review.

    Science.gov (United States)

    Mie, Axel; Andersen, Helle Raun; Gunnarsson, Stefan; Kahl, Johannes; Kesse-Guyot, Emmanuelle; Rembiałkowska, Ewa; Quaglio, Gianluca; Grandjean, Philippe

    2017-10-27

    This review summarises existing evidence on the impact of organic food on human health. It compares organic vs. conventional food production with respect to parameters important to human health and discusses the potential impact of organic management practices with an emphasis on EU conditions. Organic food consumption may reduce the risk of allergic disease and of overweight and obesity, but the evidence is not conclusive due to likely residual confounding, as consumers of organic food tend to have healthier lifestyles overall. However, animal experiments suggest that identically composed feed from organic or conventional production impacts in different ways on growth and development. In organic agriculture, the use of pesticides is restricted, while residues in conventional fruits and vegetables constitute the main source of human pesticide exposures. Epidemiological studies have reported adverse effects of certain pesticides on children's cognitive development at current levels of exposure, but these data have so far not been applied in formal risk assessments of individual pesticides. Differences in the composition between organic and conventional crops are limited, such as a modestly higher content of phenolic compounds in organic fruit and vegetables, and likely also a lower content of cadmium in organic cereal crops. Organic dairy products, and perhaps also meats, have a higher content of omega-3 fatty acids compared to conventional products. However, these differences are likely of marginal nutritional significance. Of greater concern is the prevalent use of antibiotics in conventional animal production as a key driver of antibiotic resistance in society; antibiotic use is less intensive in organic production. Overall, this review emphasises several documented and likely human health benefits associated with organic food production, and application of such production methods is likely to be beneficial within conventional agriculture, e.g., in integrated

  9. 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. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  10. 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. .

  11. Two organizing principles of vocal production: Implications for nonhuman and human primates.

    Science.gov (United States)

    Owren, Michael J; Amoss, R Toby; Rendall, Drew

    2011-06-01

    Vocal communication in nonhuman primates receives considerable research attention, with many investigators arguing for similarities between this calling and speech in humans. Data from development and neural organization show a central role of affect in monkey and ape sounds, however, suggesting that their calls are homologous to spontaneous human emotional vocalizations while having little relation to spoken language. Based on this evidence, we propose two principles that can be useful in evaluating the many and disparate empirical findings that bear on the nature of vocal production in nonhuman and human primates. One principle distinguishes production-first from reception-first vocal development, referring to the markedly different role of auditory-motor experience in each case. The second highlights a phenomenon dubbed dual neural pathways, specifically that when a species with an existing vocal system evolves a new functionally distinct vocalization capability, it occurs through emergence of a second parallel neural pathway rather than through expansion of the extant circuitry. With these principles as a backdrop, we review evidence of acoustic modification of calling associated with background noise, conditioning effects, audience composition, and vocal convergence and divergence in nonhuman primates. Although each kind of evidence has been interpreted to show flexible cognitively mediated control over vocal production, we suggest that most are more consistent with affectively grounded mechanisms. The lone exception is production of simple, novel sounds in great apes, which is argued to reveal at least some degree of volitional vocal control. If also present in early hominins, the cortically based circuitry surmised to be associated with these rudimentary capabilities likely also provided the substrate for later emergence of the neural pathway allowing volitional production in modern humans. © 2010 Wiley-Liss, Inc.

  12. Gender inequality and domestic violence: implications for human immunodeficiency virus (HIV) prevention

    OpenAIRE

    Kaye, Dan K

    2004-01-01

    Domestic violence and human immunodeficiency virus (HIV) infection are problems of great public health worldwide, especially sub-Saharan Africa and much of the developing countries. This is due to their far reaching social, economic and public health consequences. The two problems have gender inequality and gender power imbalances as the driving force behind the “epidemics”. HIV infection is mainly acquired through heterosexual relations, which themselves are greatly influenced by socio-cultu...

  13. Digital companion species and eating data: Implications for theorising digital data–human assemblages

    OpenAIRE

    Deborah Lupton

    2016-01-01

    This commentary is an attempt to begin to identify and think through some of the ways in which sociocultural theory may contribute to understandings of the relationship between humans and digital data. I develop an argument that rests largely on the work of two scholars in the field of science and technology studies: Donna Haraway and Annemarie Mol. Both authors emphasised materiality and multiple ontologies in their writing. I argue that these concepts have much to offer critical data studie...

  14. Gut luminal endogenous protein: implications for the determination of ileal amino acid digestibility in humans.

    Science.gov (United States)

    Moughan, Paul J; Rutherfurd, Shane M

    2012-08-01

    The true ileal digestibility assay provides the most informative measure of digestibility to assess bioavailability of amino acids in foods for humans. To determine 'true' estimates of ileal amino acid digestibility, requires that endogenous amino acids present in digesta at the terminal ileum be quantified. The amounts of endogenous amino acids in ileal digesta can be determined after feeding an animal or human a protein-free diet (traditional approach) or by various methods after giving a protein-containing diet. When the protein-free method has been applied with adult human subjects an overall mean value (three separate studies) for endogenous ileal nitrogen flow of 800 mg N/d has been reported. This value is considerably lower than a comparable value obtained after feeding protein of 1852 mg N/d (mean of four separate studies), and thus endogenous ileal N and amino acids should be measured under conditions of protein alimentation. There is some confusion concerning the terminology used to define digestibility, with the term "true" digestibility having different adopted meanings. Here, true amino acid digestibility is defined as apparent amino acid digestibility corrected for the basal amino acid losses determined after giving either a protein-free or a protein-containing diet. Basal losses should be determined at a defined dry-matter and protein intake. The protein-free diet approach to determining endogenous amino acids is considered unphysiological and basal losses refer to ileal endogenous amino acid flows associated with digesta dry-matter flow, and not including "specific" effects of dietary factors such as non starch polysaccharides and anti nutritional factors. Arguments are advanced that the enzyme hydrolysed protein/ultra filtration method may be suitable for routine application with a cannulated pig model, to obtain physiologically-valid basal estimates of ileal endogenous amino acids to allow calculation of true ileal amino acid digestibility in the

  15. 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.

  16. 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...

  17. Cumulative Human Impacts on Coral Reefs: Assessing Risk and Management Implications for Brazilian Coral Reefs

    OpenAIRE

    Rafael A. Magris; Alana Grech; Robert L. Pressey

    2018-01-01

    Effective management of coral reefs requires strategies tailored to cope with cumulative disturbances from human activities. In Brazil, where coral reefs are a priority for conservation, intensifying threats from local and global stressors are of paramount concern to management agencies. Using a cumulative impact assessment approach, our goal was to inform management actions for coral reefs in Brazil by assessing their exposure to multiple stressors (fishing, land-based activities, coastal de...

  18. Controversies surrounding Human Papilloma Virus infection, head & neck vs oral cancer, implications for prophylaxis and treatment

    OpenAIRE

    Campisi, G.; Giovannelli, L.

    2009-01-01

    Head & Neck Cancer (HNC) represents the sixth most common malignancy worldwide and it is historically linked to well-known behavioural risk factors, i.e., tobacco smoking and/or the alcohol consumption. Recently, substantial evidence has been mounting that Human Papillomavirus (HPV) infection is playing an increasing important role in oral cancer. Because of the attention and clamor surrounding oral HPV infection and related cancers, as well as the use of HPV prophylactic vaccines, in this in...

  19. Paradigmatic approaches to studying environment and human health: (Forgotten) implications for interdisciplinary research

    OpenAIRE

    Phoenix, Cassandra; Osborne, Nicholas J.; Redshaw, Clare; Moran, Rebecca; Stahl-timmins, Will; Depledge, Michael H.; Fleming, Lora E.; Wheeler, Benedict W.

    2013-01-01

    Interdisciplinary research is increasingly promoted in a wide range of fields, especially so in the study of relationships between the environment and human health. However, many projects and research teams struggle to address exactly how researchers from a multitude of disciplinary and methodological backgrounds can best work together to maximize the value of this approach to research. In this paper, we briefly review the role of interdisciplinary research, and emphasise that it is not only ...

  20. New Perspectives on the Brain Lesion Approach - Implications for Theoretical Models of Human Memory.

    Science.gov (United States)

    Irish, Muireann; van Kesteren, Marlieke T R

    2018-03-15

    Human lesion studies represent the cornerstone of modern day neuropsychology and provide an important adjunct to functional neuroimaging methods. The study of human lesion groups with damage to distinct regions of the brain permits the identification of underlying mechanisms and structures not only associated with, but essential for, complex cognitive processes. Here, we consider a recent review by McCormick et al., 2018 in which the power of the lesion model approach is elegantly presented with respect to a host of sophisticated cognitive endeavors, including autobiographical memory, future thinking, spatial navigation, and decision-making. By comparing profiles of loss and sparing in hippocampal (HC) and ventromedial prefrontal cortex (vmPFC) lesion groups, the authors provide new insights into the underlying neuroarchitecture of these diverse cognitive functions. Building on this framework, we consider how vmPFC and HC degeneration, in the context of large-scale network dysfunction in dementia, impacts discrete facets of memory and social cognition. Notably, we find remarkable concordance between the available evidence in dementia and that of the HC and vmPFC lesion literature. We further assess the role of the prefrontal cortex in modulating aspects of spatial navigation and discuss the role of schema-related processing in the service of memory more broadly. Far from being obsolete, we contend that human lesion work occupies a crucial position in cognitive neuroscience and offers an array of exciting areas for future study within this field. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. 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.

  2. 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.

  3. Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-07-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

  4. Parent and halogenated polycyclic aromatic hydrocarbons in rice and implications for human health in China

    International Nuclear Information System (INIS)

    Ding Chao; Ni Honggang; Zeng Hui

    2012-01-01

    Rice is the staple food for approximate two thirds of the Chinese population. However, human exposure to parent and halogenated polycyclic aromatic hydrocarbons (PAHs) via rice consumption is still not clear for Chinese people so far. The goals of this work are to assess human exposure to PAHs and halogenated PAHs (HPAHs) via rice ingestion and the cancer risk for Chinese population. 16 PAHs and eight HPAHs were determined in rice samples collected from 18 provinces in China. In general terms, the general population in China was exposed to higher levels of PAHs via rice ingestion in comparison to that via cereals for other countries. The cancer risk values induced by exposure to PAHs and HPAHs for male and female on each age group were between the priority risk level (10 −4 ) and the acceptable risk level (10 −6 ). Children faced the highest cancer risk, followed by adolescents and adults. - Highlights: ► Dietary exposure to PAHs via rice ingestion for Chinese population was higher than that via cereals in other countries. ► The cancer risk induced by PAHs and HPAHs intakes via rice consumption were between 10 −6 and 10 −4 . ► Children faced the highest cancer risk, followed by adolescents and adults. ► Given all exposure routes were considered, the real cancer risk for Chinese people would be greater. - Human exposure to parent and halogenated PAHs via rice ingestion and the cancer risk for Chinese population were assessed.

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

    International Nuclear Information System (INIS)

    Liu Xiaojuan; Zhao Quanli; Sun Guoxin; Williams, Paul; Lu Xiujun; Cai Jingzhu; Liu Wenju

    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. - Highlights: ► Arsenic speciation was extracted using 1% HNO 3 in microwave. ► Inorganic arsenic was the predominant species in all of CHMs samples. ► The highest concentration of inorganic arsenic was found in the Chrysanthemum. - Inorganic arsenic was the predominant species in all of CHMs samples.

  6. Medical implications of obesity in horses--lessons for human obesity.

    Science.gov (United States)

    Johnson, Philip J; Wiedmeyer, Charles E; Messer, Nat T; Ganjam, Venkataseshu K

    2009-01-01

    There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. © Diabetes Technology Society

  7. Medical Implications of Obesity in Horses—Lessons for Human Obesity

    Science.gov (United States)

    Johnson, Philip J.; Wiedmeyer, Charles E.; Messer, Nat T.; Ganjam, Venkataseshu K.

    2009-01-01

    There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. PMID:20046661

  8. 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

  9. Mercury in soil, vegetable and human hair in a typical mining area in China: Implication for human exposure.

    Science.gov (United States)

    Jia, Qin; Zhu, Xuemei; Hao, Yaqiong; Yang, Ziliang; Wang, Qi; Fu, Haihui; Yu, Hongjin

    2018-06-01

    Concentrations of total mercury (T-Hg) and methylmercury (MeHg) in soil, vegetables, and human hair were measured in a mercury mining area in central China. T-Hg and MeHg concentrations in soil ranged from 1.53 to 1054.97mg/kg and 0.88 to 46.52μg/kg, respectively. T-Hg concentrations was correlated with total organic carbon (TOC) content (R 2 =0.50, p<0.01) and pH values (R 2 =0.21, p<0.05). A significant linear relationship was observed between MeHg concentrations and the abundance of sulfate-reducing bacteria (SRB) (R 2 =0.39, p<0.05) in soil. Soil incubation experiments amended with specific microbial stimulants and inhibitors showed that Hg methylation was derived from SRB activity. T-Hg and MeHg concentrations in vegetables were 24.79-781.02μg/kg and 0.01-0.18μg/kg, respectively; levels in the edible parts were significantly higher than in the roots (T-Hg: p<0.05; MeHg: p<0.01). Hg species concentrations in rhizosphere soil were positively correlated to those in vegetables (p<0.01), indicating that soil was an important source of Hg in vegetables. Risk assessment indicated that the consumption of vegetables could result in higher probable daily intake (PDI) of T-Hg than the provisional tolerable daily intake (PTDI) for both adults and children. In contrast, the PDI of MeHg was lower than the reference dose. T-Hg and MeHg concentrations in hair samples ranged from 1.57 to 12.61mg/kg and 0.04 to 0.94mg/kg, respectively, and MeHg concentration in hair positively related to PDI of MeHg via vegetable consumption (R 2 =0.39, p<0.05), suggesting that vegetable may pose health risk to local residents. Copyright © 2017. Published by Elsevier B.V.

  10. 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

  11. A review of mercury in Lake Victoria, East Africa: implications for human and ecosystem health.

    Science.gov (United States)

    Campbell, Linda; Dixon, D G; Hecky, R E

    2003-01-01

    Lake Victoria, East Africa, has been the site of many recent studies measuring mercury (Hg) concentrations in water, fish, sediment, soil, and humans. Most of these studies were motivated by concerns about Hg contamination from processing of gold ore on the southern shores. Total Hg (THg) concentrations in fish were usually below permissible World Health Organization (WHO) concentrations and international marketing limits and do not threaten the lucrative export industry. Nile perch 3-10 kg and most >10 kg had THg concentrations above the WHO threshold concentrations for at-risk groups (200 ng/g). Elevated THg concentrations in large Nile perch are not of major concern because Nile perch are rarely consumed by the people living on Lake Victoria and very large Nile perch are becoming increasingly rare in catches. Water THg concentrations were below Canadian drinking water guidelines but were elevated relative to those in the northern Great Lakes. Sediment and soil THg concentrations were within inter-national guidelines and are comparable to those in northern latitudes but are lower than those in the Amazon basin. Biomass burning and soil erosion are estimated to be the major sources of THg for the lake and probably constitute a larger source of THg than gold mining in Tanzania.THg concentrations in urine and hair from human volunteers indicate that while gold miners and frequent skin-bleaching cream users are at risk of inorganic mercury poisoning, the rest of the population, including fishermen, is not. Human exposure assessments demonstrated that fish consumption and soil geophagy constitute major sources of THg for humans, but the total estimated daily intake of THg was below the Health Canada tolerable daily intake (TDI) limits. The use of beauty creams containing high inorganic Hg concentrations, however, caused the estimated THg exposure to exceed the TDI. The high THg content in the hair of regular cream users supports this assessment. The nutritional

  12. Chronology of Ksar Akil (Lebanon) and Implications for the Colonization of Europe by Anatomically Modern Humans

    Science.gov (United States)

    Douka, Katerina; Bergman, Christopher A.; Hedges, Robert E. M.; Wesselingh, Frank P.; Higham, Thomas F. G.

    2013-01-01

    The Out-of-Africa model holds that anatomically modern humans (AMH) evolved and dispersed from Africa into Asia, and later Europe. Palaeoanthropological evidence from the Near East assumes great importance, but AMH remains from the region are extremely scarce. ‘Egbert’, a now-lost AMH fossil from the key site of Ksar Akil (Lebanon) and ‘Ethelruda’, a recently re-discovered fragmentary maxilla from the same site, are two rare examples where human fossils are directly linked with early Upper Palaeolithic archaeological assemblages. Here we radiocarbon date the contexts from which Egbert and Ethelruda were recovered, as well as the levels above and below the findspots. In the absence of well-preserved organic materials, we primarily used marine shell beads, often regarded as indicative of behavioural modernity. Bayesian modelling allows for the construction of a chronostratigraphic framework for Ksar Akil, which supports several conclusions. The model-generated age estimates place Egbert between 40.8–39.2 ka cal BP (68.2% prob.) and Ethelruda between 42.4–41.7 ka cal BP (68.2% prob.). This indicates that Egbert is of an age comparable to that of the oldest directly-dated European AMH (Peştera cu Oase). Ethelruda is older, but on current estimates not older than the modern human teeth from Cavallo in Italy. The dating of the so-called “transitional” or Initial Upper Palaeolithic layers of the site may indicate that the passage from the Middle to Upper Palaeolithic at Ksar Akil, and possibly in the wider northern Levant, occurred later than previously estimated, casting some doubts on the assumed singular role of the region as a locus for human dispersals into Europe. Finally, tentative interpretations of the fossil's taxonomy, combined with the chronometric dating of Ethelruda's context, provides evidence that the transitional/IUP industries of Europe and the Levant, or at least some of them, may be the result of early modern human migration(s). PMID

  13. Arsenic in garden soils and vegetable crops in Cornwall, England: Implications for human health.

    Science.gov (United States)

    Xu, J; Thornton, I

    1985-12-01

    Total concentrations of arsenic in surface (0-15cm) garden soils in the historical mining area of Hayle-Camborne-Godolphin, Cornwall, England are large and range widely (144-892 μg/g). Amounts of water soluble and acid-fluoride extractable soil arsenic are significantly correlated with total content.Examination of 6 salad and vegetable crops grown in 32 gardens has shown arsenic concentrations in the edible tissues to be only slightly elevated. There were strong correlations between arsenic in beetroot, lettuce, onion and peas and soil arsenic (total, water soluble and acid extractable). Regression equations have been calculated. Ridge regression analysis applied to test the importance of other soil variables has shown both iron and phosphorus to influence the uptake of arsenic.Arsenic in all the vegetables sampled was below the statutory limit in the U.K. of 1 mg/kg fresh weight. Implications for health should be assessed in relation to other exposure routesvia water, air and directly ingested dust and soil.

  14. Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors

    International Nuclear Information System (INIS)

    Ruemke, H.C.; Terpstra, F.G.; Huis, B.; Out, T.A.; Zeijlemaker, W.P.

    1982-01-01

    When human peripheral blood lymphocytes (PBL) are cultured in the presence of irradiated allogeneic lymphocytes, the resulting mixed lymphocyte reaction (MLR) leads to the secretion into the supernatant of substantial amounts of IgM and IgG, derived from nonirradiated responder B lymphocytes. Our data indicate that stimulation to Ig production by responder B cells may result from different types of of interactions. First, B cells and monocytes among the irradiated stimulator cells activate T responder B cells to produce Ig; second, ''responder'' B cells activate irradiated ''stimulator'' T cells, leading to a ''helper'' signal, back to the responder B cells and leading to Ig production. The latter system is radiosensitive, because allogeneic T cells, irradiated at a dose of 4000 rad or more, failed to induce Ig production by responder B cells. In some combinations of human allogeneic lymphocytes, the co-culture of the cells leads to inhibition of Ig production, both in the presence and in the absence of PWM. Thus, co-culture of allogeneic cells may cause ''positive'' as well as ''negative'' allogeneic effects. The implications of these findings for the interpretation of co-cultures that are aimed at establishing defects in lymphocytes from patients with, for example, immunodeficiencies, who fail to produce Ig in the presence of PWM are discussed

  15. Bat Hunting and Bat-Human Interactions in Bangladeshi Villages: Implications for Zoonotic Disease Transmission and Bat Conservation.

    Science.gov (United States)

    Openshaw, J J; Hegde, S; Sazzad, H M S; Khan, S U; Hossain, M J; Epstein, J H; Daszak, P; Gurley, E S; Luby, S P

    2017-08-01

    Bats are an important reservoir for emerging zoonotic pathogens. Close human-bat interactions, including the sharing of living spaces and hunting and butchering of bats for food and medicines, may lead to spillover of zoonotic disease into human populations. We used bat exposure and environmental data gathered from 207 Bangladeshi villages to characterize bat exposures and hunting in Bangladesh. Eleven percent of households reported having a bat roost near their homes, 65% reported seeing bats flying over their households at dusk, and 31% reported seeing bats inside their compounds or courtyard areas. Twenty percent of households reported that members had at least daily exposure to bats. Bat hunting occurred in 49% of the villages surveyed and was more likely to occur in households that reported nearby bat roosts (adjusted prevalence ratio [aPR] 2.3, 95% CI 1.1-4.9) and villages located in north-west (aPR 7.5, 95% CI 2.5-23.0) and south-west (aPR 6.8, 95% CI 2.1-21.6) regions. Our results suggest high exposure to bats and widespread hunting throughout Bangladesh. This has implications for both zoonotic disease spillover and bat conservation. © 2016 Blackwell Verlag GmbH.

  16. Urinary bisphenol A concentrations and their implications for human exposure in several Asian countries.

    Science.gov (United States)

    Zhang, Zifeng; Alomirah, Husam; Cho, Hyeon-Seo; Li, Yi-Fan; Liao, Chunyang; Minh, Tu Binh; Mohd, Mustafa Ali; Nakata, Haruhiko; Ren, Nanqi; Kannan, Kurunthachalam

    2011-08-15

    Bisphenol A (BPA) is an industrial chemical used in the manufacture of polycarbonate plastics and epoxy resins. Due to the potential of this compound to disrupt normal endocrinal functions, concerns over human exposure to BPA have been raised. Although several studies have reported human exposure to BPA in Western nations, little is known about exposure in Asian countries. In this study, we determined total urinary BPA concentrations (free plus conjugated) in 296 urine samples (male/female: 153/143) collected from the general population in seven Asian countries, China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam, using high-performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). On the basis of urinary BPA concentrations, we estimated the total daily intake. The results indicated that BPA was detected in 94.3% of the samples analyzed, at concentrations ranging from Malaysia (1.06 ng/mL, 2.31 μg/g), and Japan (0.95 ng/mL, 0.58 μg/g). Among the five age groups studied (≤ 19, 20-29, 30-39, 40-49, and ≥ 50 years), the highest median concentration of BPA was found in urine samples from the age group of ≤ 19 years. There was no significant difference in BPA concentrations between genders (male and female) or domicile of residence (rural and urban). The estimated median daily intakes of BPA for the populations in Kuwait, Korea, India, China, Vietnam, Malaysia, and Japan were 5.19, 3.69, 2.90, 2.13, 2.01, 1.80, and 1.61 μg/day, respectively. The estimated daily intake of BPA in the seven Asian countries was significantly lower than the tolerable daily intake recommended by the U.S. Environmental Protection Agency. This is the first study to document the occurrence of and human exposure to BPA in several Asian countries.

  17. 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.

  18. Middle Palaeolithic flint procurement in Central Mediterranean Iberia: Implications for human mobility

    Directory of Open Access Journals (Sweden)

    Aleix Eixea

    2014-03-01

    Full Text Available Different flint types from the Middle Palaeolithic site of Abrigo de la Quebrada (Chelva, Valencia are characterized,  both macro- and microscopically, and compared with types found at other localities in the region. Although procurement predominantly concerned the immediate vicinity of sites, our results show the presence of the same types in assemblages separated by distances of up to 120 km. The long distances involved are suggestive of a pattern of North-South mobility of human groups along the coastline of central Mediterranean Iberia.

  19. 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).

  20. 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)

  1. 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.

  2. Vector movement underlies avian malaria at upper elevation in Hawaii: implications for transmission of human malaria.

    Science.gov (United States)

    Freed, Leonard A; Cann, Rebecca L

    2013-11-01

    With climate warming, malaria in humans and birds at upper elevations is an emerging infectious disease because development of the parasite in the mosquito vector and vector life history are both temperature dependent. An enhanced-mosquito-movement model from climate warming predicts increased transmission of malaria at upper elevation sites that are too cool for parasite development in the mosquito vector. We evaluate this model with avian malaria (Plasmodium relictum) at 1,900-m elevation on the Island of Hawaii, with air temperatures too low for sporogony in the vector (Culex quinquefasciatus). On a well-defined site over a 14-year period, 10 of 14 species of native and introduced birds became infected, several epizootics occurred, and the increase in prevalence was driven more by resident species than by mobile species that could have acquired their infections at lower elevations. Greater movement of infectious mosquitoes from lower elevations now permits avian malaria to spread at 1,900 m in Hawaii, in advance of climate warming at that elevation. The increase in malaria at upper elevations due to dispersal of infectious mosquitoes is a real alternative to temperature for the increased incidence of human malaria in tropical highlands.

  3. A model of fluid and solute exchange in the human: validation and implications.

    Science.gov (United States)

    Bert, J L; Gyenge, C C; Bowen, B D; Reed, R K; Lund, T

    2000-11-01

    In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

  4. Legacy and alternative halogenated flame retardants in human milk in Europe: Implications for children's health.

    Science.gov (United States)

    Čechová, Eliška; Vojta, Šimon; Kukučka, Petr; Kočan, Anton; Trnovec, Tomáš; Murínová, Ľubica Palkovičová; de Cock, Marijke; van de Bor, Margot; Askevold, Joakim; Eggesbø, Merete; Scheringer, Martin

    2017-11-01

    In this study, 10 polybrominated diphenyl ethers (PBDEs) and 19 alternative halogenated flame retardants (AFRs) were determined in >450 human milk samples across three European countries, representing northern, western and eastern Europe. This study provides first insights into the occurrence of selected AFRs in mother milk samples and compares them among three European countries. Sums of median concentrations of the most frequently detected PBDEs were 2.16, 0.88 and 0.45ngg -1 lipid weight (lw) in Norway, the Netherlands and Slovakia, respectively. The sum of the concentrations of AFRs ranged from 0.14 to 0.25ngg -1 lw in all countries, which was 2 to 15 times less compared to Σ 7 PBDEs. The Penta-BDE replacement, bis(2-ethylhexyl) tetrabromophthalate, BEH-TEBP, was present at the greatest concentrations of any of the AFRs and in some samples exceeded concentrations of BDE 47 and BDE 153. Four AFRs including bromobenzenes (hexabromobenzene, pentabromobenzene, pentabromotoluene) and another Penta-BDE replacement (2-ethylhexyl-2,3,4,5-tetrabromobenzoate, EH-TBB) were detected in >42% of all human milk samples. Because of the potential developmental neurotoxicity of the halogenated flame retardants, infant dietary intakes via breastfeeding were estimated; in four cases the intakes of BDE 47 exceeded the reference dose indicating that the present concentrations may pose a risk for children. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 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.

  6. The Human Gut Phage Community and Its Implications for Health and Disease.

    Science.gov (United States)

    Manrique, Pilar; Dills, Michael; Young, Mark J

    2017-06-08

    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.

  7. Characterizing pollutant emissions from mosquito repellents incenses and implications in risk assessment of human health.

    Science.gov (United States)

    Wang, Lina; Zheng, Xinran; Stevanovic, Svetlana; Xiang, Zhiyuan; Liu, Jing; Shi, Huiwen; Liu, Jing; Yu, Mingzhou; Zhu, Chun

    2018-01-01

    Mosquito-repellent incense is one of the most popular products used for dispelling mosquitos during summer in China. It releases large amounts of particulate and gaseous pollutants which constitute a potential hazard to human health. We conducted chamber experiment to characterize major pollutants from three types of mosquito-repellent incenses, further assessed the size-fractionated deposition in human respiratory system, and evaluated the indoor removing efficiency by fresh air. Results showed that the released pollutant concentrations were greater than permissible levels in regulations in GB3095-2012, as well as suggested by the World Health Organization (WHO). Formaldehyde accounted for 10-20% of the total amount of pollutants. Fine particles dominated in the total particulate concentrations. Geometric standard deviation (GSD) of particle number size distributions was in the range of 1.45-1.93. Count median diameter (CMD) ranged from 100 to 500 nm. Emission rates, burning rates and emission factors of both particulate and gaseous pollutants were compared and discussed. The deposition fractions in pulmonary airway from the disc solid types reached up to 52.7% of the total deposition, and the largest deposition appeared on juvenile group. Computational Fluid Dynamics (CFD) modellings indicated air-conditioner on and windows closed was the worst case. The highest concentration was 180-200 times over the standard limit. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications

    Directory of Open Access Journals (Sweden)

    Zetterberg Henrik

    2004-02-01

    Full Text Available Abstract The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy.

  9. Ghrelin stimulates angiogenesis in human microvascular endothelial cells: Implications beyond GH release

    International Nuclear Information System (INIS)

    Li Aihua; Cheng Guangli; Zhu Genghui; Tarnawski, Andrzej S.

    2007-01-01

    Ghrelin, a peptide hormone isolated from the stomach, releases growth hormone and stimulates appetite. Ghrelin is also expressed in pancreas, kidneys, cardiovascular system and in endothelial cells. The precise role of ghrelin in endothelial cell functions remains unknown. We examined the expression of ghrelin and its receptor (GHSR1) mRNAs and proteins in human microvascular endothelial cells (HMVEC) and determined whether ghrelin affects in these cells proliferation, migration and in vitro angiogenesis; and whether MAPK/ERK2 signaling is important for the latter action. We found that ghrelin and GHSR1 are constitutively expressed in HMVEC. Treatment of HMVEC with exogenous ghrelin significantly increased in these cells proliferation, migration, in vitro angiogenesis and ERK2 phosphorylation. MEK/ERK2 inhibitor, PD 98059 abolished ghrelin-induced in vitro angiogenesis. This is First demonstration that ghrelin and its receptor are expressed in human microvascular endothelial cells and that ghrelin stimulates HMVEC proliferation, migration, and angiogenesis through activation of ERK2 signaling

  10. Medical Hydrogeology of Asian Deltas: Status of Groundwater Toxicants and Nutrients, and Implications for Human Health.

    Science.gov (United States)

    Hoque, Mohammad A; Butler, Adrian P

    2015-12-26

    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.

  11. Human mast cell and airway smooth muscle cell interactions: implications for asthma.

    Science.gov (United States)

    Page, S; Ammit, A J; Black, J L; Armour, C L

    2001-12-01

    Asthma is characterized by inflammation, hyperresponsiveness, and remodeling of the airway. Human mast cells (HMCs) play a central role in all of these changes by releasing mediators that cause exaggerated bronchoconstriction, induce human airway smooth muscle (HASM) cell proliferation, and recruit and activate inflammatory cells. Moreover, the number of HMCs present on asthmatic HASM is increased compared with that on nonasthmatic HASM. HASM cells also have the potential to actively participate in the inflammatory process by synthesizing cytokines and chemokines and expressing surface molecules, which have the capacity to perpetuate the inflammatory mechanisms present in asthma. This review specifically examines how the mediators of HMCs have the capacity to modulate many functions of HASM; how the synthetic function of HASM, particularly through the release and expression of stem cell factor, has the potential to influence HMC number and activation in an extraordinarily potent and proinflammatory manner; and how these interactions between HMCs and HASM have potential consequences for airway structure and inflammation relevant to the disease process of asthma.

  12. 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.

  13. High adult mortality among Hiwi hunter-gatherers: implications for human evolution.

    Science.gov (United States)

    Hill, Kim; Hurtado, A M; Walker, R S

    2007-04-01

    Extant apes experience early sexual maturity and short life spans relative to modern humans. Both of these traits and others are linked by life-history theory to mortality rates experienced at different ages by our hominin ancestors. However, currently there is a great deal of debate concerning hominin mortality profiles at different periods of evolutionary history. Observed rates and causes of mortality in modern hunter-gatherers may provide information about Upper Paleolithic mortality that can be compared to indirect evidence from the fossil record, yet little is published about causes and rates of mortality in foraging societies around the world. To our knowledge, interview-based life tables for recent hunter-gatherers are published for only four societies (Ache, Agta, Hadza, and Ju/'hoansi). Here, we present mortality data for a fifth group, the Hiwi hunter-gatherers of Venezuela. The results show comparatively high death rates among the Hiwi and highlight differences in mortality rates among hunter-gatherer societies. The high levels of conspecific violence and adult mortality in the Hiwi may better represent Paleolithic human demographics than do the lower, disease-based death rates reported in the most frequently cited forager studies.

  14. The use of personal hair dye and its implications for human health.

    Science.gov (United States)

    Kim, Ki-Hyun; Kabir, Ehsanul; Jahan, Shamin Ara

    2016-01-01

    Hair dye products now represent one of the most rapidly growing beauty and personal care industries as both men and women commonly change hair color to enhance youth and beauty and to follow fashion trends. Irrespective of economic and education status, people dye their hair to emphasize the importance given to appearance. Despite adverse reactions, many people continue dyeing mainly for cosmetic purposes. This paper provides a comprehensive review on various aspects of hair dying products, especially with respect to the hair-coloring process, classification, chemical ingredients, possible human health impacts, and regulations. Permanent hair dye, which is the most commonly used product type, is formed by an oxidative process involving arylamines to bring about concerns with long-term exposure. Hence, significant efforts have been put to understand the possible side effects of such exposure including cancer risk. However, hair dyes and their ingredients are mainly identified to have moderate to low acute toxicity such as the cause of allergic contact dermatitis. Although some hair dye components are reported to be carcinogenic in animals, such evidence is not consistent enough in the case of human studies. Consequently, further research is desirable to critically address the significance of this issue, especially with respect to the safety of hair dye ingredients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. New genes expressed in human brains: implications for annotating evolving genomes.

    Science.gov (United States)

    Zhang, Yong E; Landback, Patrick; Vibranovski, Maria; Long, Manyuan

    2012-11-01

    New genes have frequently formed and spread to fixation in a wide variety of organisms, constituting abundant sets of lineage-specific genes. It was recently reported that an excess of primate-specific and human-specific genes were upregulated in the brains of fetuses and infants, and especially in the prefrontal cortex, which is involved in cognition. These findings reveal the prevalent addition of new genetic components to the transcriptome of the human brain. More generally, these findings suggest that genomes are continually evolving in both sequence and content, eroding the conservation endowed by common ancestry. Despite increasing recognition of the importance of new genes, we highlight here that these genes are still seriously under-characterized in functional studies and that new gene annotation is inconsistent in current practice. We propose an integrative approach to annotate new genes, taking advantage of functional and evolutionary genomic methods. We finally discuss how the refinement of new gene annotation will be important for the detection of evolutionary forces governing new gene origination. Copyright © 2012 WILEY Periodicals, Inc.

  16. Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

    Science.gov (United States)

    Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

    2015-01-01

    Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

  17. Kalirin, a key player in synapse formation, is implicated in human diseases.

    Science.gov (United States)

    Mandela, Prashant; Ma, Xin-Ming

    2012-01-01

    Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function.

  18. Human geomorphic footprint and global geomorphic change: implications for hydrogeomorphic hazards

    Science.gov (United States)

    Remondo, Juan

    2010-05-01

    The human geomorphic footprint (HGF), expressed as the area affected by the construction of new 'anthropogeoforms' or the volume of geologic materials directly or indirectly displaced by human action has grown considerably in the last decades. Available data suggest that the present HGF is roughly 50,000 km2 a-1 of new anthropogeoforms and 300 x109 t a-1 of solid materials transferred from one part of the earth's surface to another. The latter represents a 'technological denudation' that could be 1-2 orders of magnitude greater than denudation by natural agents or sediment transport by the world's rivers. This implies a profound modification of geomorphic processes that produces a series of often disregarded environmental consequences. Some of those can by directly linked to excavation/accumulation activities and are essentially local, but in other cases the possible relationship appears to be more indirect and could have a widespread character. The transformation of land surface by human action is shown not only by landform construction and transfer of geologic materials, but also by land-use change in general and modification of the characteristics of the surface layer. This seems to affect both the hydrologic response and the sensitivity of that surface layer to different geomorphic agents. The magnitude of the above mentioned modification is logically related to the intensity of human activities, themselves related to the number of people on the planet and their economic and technological capabilities, which grow practically in all regions of the planet. It is thus reasonable to expect that the HGF and its effects should grow with time. If this were so, we should expect to find evidences of a general acceleration of geomorphic processes in the world that could represent a 'global geomorphic change'. The final expression of geomorphic processes, which could be used to test that hypothesis, is sediment generation and deposition. Data are presented on

  19. High Prevalence of Hyper-Aerotolerant Campylobacter jejuni in Retail Poultry with Potential Implication in Human Infection.

    Science.gov (United States)

    Oh, Euna; McMullen, Lynn; Jeon, Byeonghwa

    2015-01-01

    Campylobacter jejuni is a leading cause of foodborne illnesses around the world. Since C. jejuni is microaerophilic and sensitive to oxygen, aerotolerance is important in the transmission of C. jejuni to humans via foods under aerobic conditions. In this study, 70 C. jejuni strains were isolated from retail raw chicken meats and were subject to multilocus sequence typing (MLST) analysis. In the aerotolerance testing by aerobic shaking at 200 rpm, 50 (71.4%) isolates survived after 12 h (i.e., aerotolerant), whereas 20 (28.6%) isolates did not (i.e., aerosensitive). Interestingly, further aerobic cultivation showed that 25 (35.7%) isolates still survived even after 24 h of vigorous aerobic shaking (i.e., hyper-aerotolerant). Compared to aerosensitive strains, the hyper-aerotolerant strains exhibited increased resistance to oxidative stress, both peroxide and superoxide. A mutation of ahpC in hyper-aerotolerant strains significantly impaired aerotolerance, indicating oxidative stress defense plays an important role in hyper-aerotolerance. The aerotolerant and hyper-aerotolerant strains were primarily classified into MLST clonal complexes (CCs)-21 and -45, which are known to be the major CCs implicated in human gastroenteritis. Compared to the aerosensitive strains, CC-21 was more dominant than CC-45 in aerotolerant and hyper-aerotolerant strains. The findings in this study revealed that hyper-aerotolerant C. jejuni is highly prevalent in raw chicken meats. The enhanced aerotolerance in C. jejuni would impact human infection by increasing possibilities of the foodborne transmission of C. jejuni under aerobic conditions.

  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. 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.

    2015-01-01

    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/m2). 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 (P 30%). 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. PMID:21520059

  2. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    International Nuclear Information System (INIS)

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-01-01

    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 2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F 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

  3. 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.

  4. Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

    Science.gov (United States)

    Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

    2010-01-01

    Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be

  5. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans.

    Science.gov (United States)

    List, James F; Whaley, Jean M

    2011-03-01

    Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve β-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing.

  6. Organizational change and human expertise in nuclear power plants: some implications for training and error prevention

    International Nuclear Information System (INIS)

    Masson, M.; Malaise, N.; Housiaux, A.; Keyser, V. de

    1993-01-01

    Reliability and safety are two very important goals, which depend on technical and organizational factors, but also on human expertise. How to ensure a safe functioning of a nuclear power plant in a changing context, and what might be the role and aspects of training and transfer of knowledge? These are the questions we shall deal with in this paper, on the basis of two field studies. The two field studies stress the needs for setting up case based training, which best ensure the acquisition of know-how. Furthermore, as shown by the second one, gaining expertise involves developing large repertoires of highly skilled, semi-routinized activities. Supporting expert operators not only should tackle problem solving activities but should thus also include the prevention of routine errors, which go along with skill acquisition. (orig.)

  7. Interaction of Human Enteric Viruses with Microbial Compounds: Implication for Virus Persistence and Disinfection Treatments.

    Science.gov (United States)

    Waldman, Prunelle; Meseguer, Alba; Lucas, Françoise; Moulin, Laurent; Wurtzer, Sébastien

    2017-12-05

    Although the interaction between phages and bacteria has already been well described, it only recently emerged that human viruses also interact with bacteria in the mammalian gut. We studied whether this interaction could occur in tap water and thus confer enteric viruses protection against temperature and the classical disinfection treatments used in drinking water production. We demonstrated that the addition of lipopolysaccharide or peptidoglycan of bacterial origin to enterovirus provides thermal protection through stabilization of the viral capsid. This interaction plays a role when viruses are exposed to disinfection that targets the capsid, but less so when the virus genome is directly targeted. The interaction seems to be serotype-specific, suggesting that the capsid protein sequence could be important. The protection is linked to a direct association between viral particles and bacterial compounds as observed by microscopy. These results show that bacterial compounds present in the environment can affect virus inactivation.

  8. 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.

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

    DEFF Research Database (Denmark)

    Richter, Erik; Ruderman, Neil B.

    2009-01-01

    the acute and chronic effects of exercise on AMPK activity in skeletal muscle and other tissues. We also discuss the potential role of AMPK activation in mediating the prevention and treatment by exercise of specific disorders associated with the metabolic syndrome, including Type 2 diabetes and Alzheimer......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...... the AMP/ATP ratio. When activated, AMPK stimulates energy-generating processes such as glucose uptake and fatty acid oxidation and decreases energy-consuming processes such as protein and lipid synthesis. Exercise is perhaps the most powerful physiological activator of AMPK and a unique model for studying...

  10. Homogentisate 1,2 dioxygenase is expressed in human osteoarticular cells: implications in alkaptonuria.

    Science.gov (United States)

    Laschi, Marcella; Tinti, Laura; Braconi, Daniela; Millucci, Lia; Ghezzi, Lorenzo; Amato, Loredana; Selvi, Enrico; Spreafico, Adriano; Bernardini, Giulia; Santucci, Annalisa

    2012-09-01

    Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. Copyright © 2011 Wiley Periodicals, Inc.

  11. Bringing Darwin into the social sciences and the humanities: cultural evolution and its philosophical implications.

    Science.gov (United States)

    Blancke, Stefaan; Denis, Gilles

    2018-04-10

    In the field of cultural evolution it is generally assumed that the study of culture and cultural change would benefit enormously from being informed by evolutionary thinking. Recently, however, there has been much debate about what this "being informed" means. According to the standard view, an interesting analogy obtains between cultural and biological evolution. In the literature, however, the analogy is interpreted and used in at least three distinct, but interrelated ways. We provide a taxonomy in order to clarify these different meanings. Subsequently, we discuss the alternatives model of cultural attraction theory and memetics, which both challenge basic assumptions of the standard view. Finally, we briefly summarize the contributions to the special issue on Darwin in the Humanities and the Social Sciences, which is the result of a collaborative project between scholars and scientists from the universities of Lille and Ghent. Furthermore, we explain how they add to the discussions about the integration of evolutionary thinking and the study of culture.

  12. TRPV1 channels in human skeletal muscle feed arteries: implications for vascular function.

    Science.gov (United States)

    Ives, Stephen J; Park, Song Young; Kwon, Oh Sung; Gifford, Jayson R; Andtbacka, Robert H I; Hyngstrom, John R; Richardson, Russell S

    2017-09-01

    What is the central question of this study? We sought to determine whether human skeletal muscle feed arteries (SFMAs) express TRPV 1 channels and what role they play in modulating vascular function. What is the main finding and its importance? Human SMFAs do express functional TRPV 1 channels that modulate vascular function, specifically opposing α-adrenergic receptor-mediated vasocontraction and potentiating vasorelaxation, in an endothelium-dependent manner, as evidenced by the α 1 -receptor-mediated responses. Thus, the vasodilatory role of TRPV 1 channels, and their ligand capsaicin, could be a potential therapeutic target for improving vascular function. Additionally, given the 'sympatholytic' effect of TRPV 1 activation and known endogenous activators (anandamide, reactive oxygen species, H + , etc.), TRPV 1 channels might contribute to functional sympatholysis during exercise. To examine the role of the transient receptor potential vanilloid type 1 (TRPV 1 ) ion channel in the vascular function of human skeletal muscle feed arteries (SMFAs) and whether activation of this heat-sensitive receptor could be involved in modulating vascular function, SMFAs from 16 humans (63 ± 5 years old, range 41-89 years) were studied using wire myography with capsaicin (TRPV 1 agonist) and without (control). Specifically, phenylephrine (α 1 -adrenergic receptor agonist), dexmedetomidine (α 2 -adrenergic receptor agonist), ACh and sodium nitroprusside concentration-response curves were established to assess the role of TRPV 1 channels in α-receptor-mediated vasocontraction as well as endothelium-dependent and -independent vasorelaxation, respectively. Compared with control conditions, capsaicin significantly attenuated maximal vasocontraction in response to phenylephrine [control, 52 ± 8% length-tension max (LT max ) and capsaicin, 21 ± 5%LT max ] and dexmedetomidine (control, 29 ± 12%LT max and capsaicin, 2 ± 3%LT max ), while robustly enhancing maximal

  13. Effects of Olive Oil on TNF-α and IL-6 in Humans: Implication in Obesity and Frailty.

    Science.gov (United States)

    Yarla, Nagendra S; Polito, Angela; Peluso, Ilaria

    2018-01-01

    Tumor necrosis factor-alpha (TNF)-α and interleukin (IL)-6 are important mediators of chronic low-grade systemic inflammation. The latter plays a central role in several obesity-related pathologies, such as diabetes, metabolic syndrome and cardiovascular diseases. Besides, these cytokines have been also implicated in geriatric and cancer-induced anorexia, cachexia, sarcopenia and frailty. Potential interventions for both obesity and frailty include dietary advice and nutraceuticals. In this context, the consumption of olive oil (OO) has been associated with the health effects of the Mediterranean diet (Med-diet). This review is aimed to discuss the OO-mediated modulation of TNF- α and IL-6 in human studies and the potential implication in obesity and frailty. The reviewed studies suggest that the improvement of postprandial TNF-α and IL-6 observed with OO consumption is affected by body mass index (BMI). The effects on TNF-α and IL-6 after medium and long-term consumptions involved many factors and the cross-talk between adipose tissue, liver, skeletal muscle and brain. Major anti-inflammatory effects were observed when OO was consumed with Med-diet, which is associated with healthy behaviors. In this context, the role of microbioma- polyphenols, diet-gene and exercise-gene interactions in the effects of OO on immune-mediated inflammatory responses involved in obesity and frailty deserves further investigation. Further studies are needed to clarify the effect of OO net of possible synergistic effects with other dietary and lifestyle factors of Mediterranean area. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening.

    Science.gov (United States)

    Katki, Hormuzd A; Cheung, Li C; Fetterman, Barbara; Castle, Philip E; Sundaram, Rajeshwari

    2015-10-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development.

  15. The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications.

    Science.gov (United States)

    Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L

    2010-02-15

    Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.

  16. 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.

  17. Surf zone entrainment, along-shore transport, and human health implications of pollution from tidal outlets

    Science.gov (United States)

    Grant, S. B.; Kim, J. H.; Jones, B. H.; Jenkins, S. A.; Wasyl, J.; Cudaback, C.

    2005-10-01

    Field experiments and modeling studies were carried out to characterize the surf zone entrainment and along-shore transport of pollution from two tidal outlets that drain into Huntington Beach and Newport Beach, popular public beaches in southern California. The surf zone entrainment and near-shore transport of pollutants from these tidal outlets appears to be controlled by prevailing wave conditions and coastal currents, and fine-scale features of the flow field around the outlets. An analysis of data from dye experiments and fecal indicator bacteria monitoring studies reveals that the along-shore flux of surf zone water is at least 50 to 300 times larger than the cross-shore flux of surf zone water. As a result, pollutants entrained in the surf zone hug the shore, where they travel significant distances parallel to the beach before diluting to extinction. Under the assumption that all surf zone pollution at Huntington Beach originates from two tidal outlets, the Santa Ana River and Talbert Marsh outlets, models of mass and momentum transport in the surf zone approximately capture the observed tidal phasing and magnitude of certain fecal indicator bacteria groups (total coliform) but not others (Escherichia coli and enterococci), implying the existence of multiple sources of, and/or multiple transport pathways for, fecal pollution at this site. The intersection of human recreation and near-shore pollution pathways implies that, from a human health perspective, special care should be taken to reduce the discharge of harmful pollutants from land-side sources of surface water runoff, such as tidal outlets and storm drains.

  18. Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

    Science.gov (United States)

    Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

    2017-04-01

    Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

  19. 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.

  20. Characterization of a human peptide deformylase: implications for antibacterial drug design.

    Science.gov (United States)

    Nguyen, Kiet T; Hu, Xubo; Colton, Craig; Chakrabarti, Ratna; Zhu, Michael X; Pei, Dehua

    2003-08-26

    Ribosomal protein synthesis in eubacteria and eukaryotic organelles initiates with an N-formylmethionyl-tRNA(i), resulting in N-terminal formylation of all nascent polypeptides. Peptide deformylase (PDF) catalyzes the subsequent removal of the N-terminal formyl group from the majority of bacterial proteins. Deformylation was for a long time thought to be a feature unique to the prokaryotes, making PDF an attractive target for designing novel antibiotics. However, recent genomic sequencing has revealed PDF-like sequences in many eukaryotes, including man. In this work, the cDNA encoding Homo sapiens PDF (HsPDF) has been cloned and a truncated form that lacks the N-terminal 58-amino-acid targeting sequence was overexpressed in Escherichia coli. The recombinant, Co(2+)-substituted protein is catalytically active in deformylating N-formylated peptides, shares many of the properties of bacterial PDF, and is strongly inhibited by specific PDF inhibitors. Expression of HsPDF fused to the enhanced green fluorescence protein in human embryonic kidney cells revealed its location in the mitochondrion. However, HsPDF is much less active than its bacterial counterpart, providing a possible explanation for the apparent lack of deformylation in the mammalian mitochondria. The lower catalytic activity is at least partially due to mutation of a highly conserved residue (Leu-91 in E. coli PDF) in mammalian PDF. PDF inhibitors had no detectable effect on two different human cell lines. These results suggest that HsPDF is likely an evolutional remnant without any functional role in protein formylation/deformylation and validates PDF as an excellent target for antibacterial drug design.

  1. TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells

    Directory of Open Access Journals (Sweden)

    Nikolett Sándor

    2015-10-01

    Full Text Available Tumor protein 53-induced nuclear protein-1 (TP53inp1 is expressed by activation via p53 and p73. The purpose of our study was to investigate the role of TP53inp1 in response of fibroblasts to ionizing radiation. γ-Ray radiation dose-dependently induces the expression of TP53inp1 in human immortalized fibroblast (F11hT cells. Stable silencing of TP53inp1 was done via lentiviral transfection of shRNA in F11hT cells. After irradiation the clonogenic survival of TP53inp1 knockdown (F11hT-shTP cells was compared to cells transfected with non-targeting (NT shRNA. Radiation-induced senescence was measured by SA-β-Gal staining and autophagy was detected by Acridine Orange dye and microtubule-associated protein-1 light chain 3 (LC3B immunostaining. The expression of TP53inp1, GDF-15, and CDKN1A and alterations in radiation induced mitochondrial DNA deletions were evaluated by qPCR. TP53inp1 was required for radiation (IR induced maximal elevation of CDKN1A and GDF-15 expressions. Mitochondrial DNA deletions were increased and autophagy was deregulated following irradiation in the absence of TP53inp1. Finally, we showed that silencing of TP53inp1 enhances the radiation sensitivity of fibroblast cells. These data suggest functional roles for TP53inp1 in radiation-induced autophagy and survival. Taken together, we suppose that silencing of TP53inp1 leads radiation induced autophagy impairment and induces accumulation of damaged mitochondria in primary human fibroblasts.

  2. 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.

  3. Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation.

    Science.gov (United States)

    Sackett, S D; Brown, M E; Tremmel, D M; Ellis, T; Burlingham, W J; Odorico, J S

    2016-04-01

    Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs. autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Detection experiments with humans implicate visual predation as a driver of colour polymorphism dynamics in pygmy grasshoppers

    Science.gov (United States)

    2013-01-01

    Background Animal colour patterns offer good model systems for studies of biodiversity and evolution of local adaptations. An increasingly popular approach to study the role of selection for camouflage for evolutionary trajectories of animal colour patterns is to present images of prey on paper or computer screens to human ‘predators’. Yet, few attempts have been made to confirm that rates of detection by humans can predict patterns of selection and evolutionary modifications of prey colour patterns in nature. In this study, we first analyzed encounters between human ‘predators’ and images of natural black, grey and striped colour morphs of the polymorphic Tetrix subulata pygmy grasshoppers presented on background images of unburnt, intermediate or completely burnt natural habitats. Next, we compared detection rates with estimates of capture probabilities and survival of free-ranging grasshoppers, and with estimates of relative morph frequencies in natural populations. Results The proportion of grasshoppers that were detected and time to detection depended on both the colour pattern of the prey and on the type of visual background. Grasshoppers were detected more often and faster on unburnt backgrounds than on 50% and 100% burnt backgrounds. Striped prey were detected less often than grey or black prey on unburnt backgrounds; grey prey were detected more often than black or striped prey on 50% burnt backgrounds; and black prey were detected less often than grey prey on 100% burnt backgrounds. Rates of detection mirrored previously reported rates of capture by humans of free-ranging grasshoppers, as well as morph specific survival in the wild. Rates of detection were also correlated with frequencies of striped, black and grey morphs in samples of T. subulata from natural populations that occupied the three habitat types used for the detection experiment. Conclusions Our findings demonstrate that crypsis is background-dependent, and implicate visual predation

  5. The TCD50 and regrowth delay assay in human tumor xenografts: Differences and implications

    International Nuclear Information System (INIS)

    Budach, W.; Budach, V.; Stuschke, M.; Dinges, S.; Sack, H.

    1993-01-01

    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 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 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 50 was used in order to compare the data to previously published data from spheroids. The lowest TCD 50 was found in the lymphoma with 24.9 Gy, whereas the TCD 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 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 50 values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD 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

  6. 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

  7. SOXs in human prostate cancer: implication as progression and prognosis factors

    International Nuclear Information System (INIS)

    Zhong, Wei-de; Chen, Xi-bin; Lin, Zhuo-yuan; Deng, Ye-han; Wu, Shu-lin; He, Hui-chan; Wu, Chin-lee; Qin, Guo-qiang; Dai, Qi-shan; Han, Zhao-dong; Chen, Shan-ming; Ling, Xiao-hui; Fu, Xin; Cai, Chao; Chen, Jia-hong

    2012-01-01

    SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. Our data offer the convince

  8. 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

  9. Tripolar mitosis in human cells and embryos: occurrence, pathophysiology and medical implications.

    Science.gov (United States)

    Kalatova, Beata; Jesenska, Renata; Hlinka, Daniel; Dudas, Marek

    2015-01-01

    Tripolar mitosis is a specific case of cell division driven by typical molecular mechanisms of mitosis, but resulting in three daughter cells instead of the usual count of two. Other variants of multipolar mitosis show even more mitotic poles and are relatively rare. In nature, this phenomenon was frequently observed or suspected in multiple common cancers, infected cells, the placenta, and in early human embryos with impaired pregnancy-yielding potential. Artificial causes include radiation and various toxins. Here we combine several pieces of the most recent evidence for the existence of different types of multipolar mitosis in preimplantation embryos together with a detailed review of the literature. The related molecular and cellular mechanisms are discussed, including the regulation of centriole duplication, mitotic spindle biology, centromere functions, cell cycle checkpoints, mitotic autocorrection mechanisms, and the related complicating factors in healthy and affected cells, including post-mitotic cell-cell fusion often associated with multipolar cell division. Clinical relevance for oncology and embryo selection in assisted reproduction is also briefly discussed in this context. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. 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. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  11. Comparative pathogenesis of rabies in bats and carnivores, and implications for spillover to humans.

    Science.gov (United States)

    Begeman, Lineke; GeurtsvanKessel, Corine; Finke, Stefan; Freuling, Conrad M; Koopmans, Marion; Müller, Thomas; Ruigrok, Tom J H; Kuiken, Thijs

    2018-04-01

    Bat-acquired rabies is becoming increasingly common, and its diagnosis could be missed partly because its clinical presentation differs from that of dog-acquired rabies. We reviewed the scientific literature to compare the pathogenesis of rabies in bats and carnivores-including dogs-and related this pathogenesis to differences in the clinical presentation of bat-acquired and dog-acquired rabies in human beings. For bat-acquired rabies, we found that the histological site of exposure is usually limited to the skin, the anatomical site of exposure is more commonly the face, and the virus might be more adapted for entry via the skin than for dog-acquired rabies. These factors could help to explain several differences in clinical presentation between individuals with bat-acquired and those with dog-acquired rabies. A better understanding of these differences should improve the recording of a patient's history, enable drawing up of a more sophisticated list of clinical characteristics, and therefore obtain an earlier diagnosis of rabies after contact with a bat or carnivore that has rabies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. 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.

  13. Volcano related atmospheric toxicants in Hilo and Hawaii Volcanoes National Park: implications for human health.

    Science.gov (United States)

    Michaud, Jon-Pierre; Krupitsky, Dmitry; Grove, John S; Anderson, Bruce S

    2005-08-01

    Volcanic fog (vog) from Kilauea volcano on the island of Hawaii includes a variety of chemical species including sulfur compounds and traces of metals such as mercury. The metal species seen tended to be in the nanograms per cubic meter range, whereas oxides of sulfur: SO2 and SO3 and sulfate aerosols, were in the range of micrograms per cubic meter and rarely even as high as a few milligrams per cubic meter of air (nominally ppb to ppm). These sulfur species are being investigated for associations with both acute and chronic changes in human health status. The sulfate aerosols tend to be less than 1 microm in diameter and tend to dominate the mass of this submicron size mode. The sulfur chemistry is dynamic, changing composition from predominantly sulfur dioxide and trioxide gasses near the volcano, to predominantly sulfate aerosols on the west side of the island. Time, concentration and composition characteristics of submicron aerosols and sulfur dioxide are described with respect to the related on-going health studies and public health management concerns. Exposures to sulfur dioxide and particulate matter equal to or less than 1 microm in size were almost always below the national ambient air quality standards (NAAQS). These standards do not however consider the acidic nature and submicron size of the aerosol, nor the possibility of the aerosol and the sulfur dioxide interacting in their toxicity. Time series plots, histograms and descriptive statistics of hourly averages give the reader a sense of some of the exposures observed.

  14. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Ontario's changing electrical sector : implications for air quality and human health

    International Nuclear Information System (INIS)

    Perrota, K.; De Leon, F.

    1999-03-01

    Concerns regarding the changes to Ontario's electricity sector and the impacts that these changes may have on the environment and public health are discussed. Two of the major changes include the implementation of the Nuclear Asset Optimization Plan, and the introduction of competition to Ontario's electrical market. Both changes could have profound impacts on air quality in Toronto and the rest of Ontario. This report recommends that the Ontario Minister of Environment and the Ontario Minister of Energy, Science and Technology establish: a regulatory framework to ensure that competition in Ontario's electrical sector does not lead to greater reliance on coal-fired generating stations and further degradation of air quality, human health and the environment in Toronto and the rest of southern Ontario; annual air emission caps for the entire electrical sector to limit the volume of air pollutants released each year; a renewable energy standard which defines the percentage of electricity that must be generated with renewable energies by electrical suppliers serving Ontario consumers; and a public benefit fund to support the promotion of energy conservation and the development of renewable energies with a surcharge on the transmission of electricity. 35 refs., 5 tabs

  16. 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 (O 3 ) concentrations. Past studies demonstrate links between O 3 exposure and health. However, knowledge gaps remain in our understanding concerning the impacts of climate change mitigation policies on O 3 concentrations and health. Using a hybrid downscaling approach, we evaluated the separate impact of climate change and emission control policies on O 3 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 O 3 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 O 3 concentrations are expected to result in over 2,200 additional premature deaths annually. The largest increases in O 3 are seen in RCP8.5 in the Northeast, the Southeast, the Central, and the West regions of the US. Additionally, when O 3 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 O 3 -related mortality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Mitochondrial DNA diversity of present-day Aboriginal Australians and implications for human evolution in Oceania.

    Science.gov (United States)

    Nagle, Nano; Ballantyne, Kaye N; van Oven, Mannis; Tyler-Smith, Chris; Xue, Yali; Wilcox, Stephen; Wilcox, Leah; Turkalov, Rust; van Oorschot, Roland A H; van Holst Pellekaan, Sheila; Schurr, Theodore G; McAllister, Peter; Williams, Lesley; Kayser, Manfred; Mitchell, R John

    2017-03-01

    Aboriginal Australians are one of the more poorly studied populations from the standpoint of human evolution and genetic diversity. Thus, to investigate their genetic diversity, the possible date of their ancestors' arrival and their relationships with neighboring populations, we analyzed mitochondrial DNA (mtDNA) diversity in a large sample of Aboriginal Australians. Selected mtDNA single-nucleotide polymorphisms and the hypervariable segment haplotypes were analyzed in 594 Aboriginal Australians drawn from locations across the continent, chiefly from regions not previously sampled. Most (~78%) samples could be assigned to mtDNA haplogroups indigenous to Australia. The indigenous haplogroups were all ancient (with estimated ages >40 000 years) and geographically widespread across the continent. The most common haplogroup was P (44%) followed by S (23%) and M42a (9%). There was some geographic structure at the haplotype level. The estimated ages of the indigenous haplogroups range from 39 000 to 55 000 years, dates that fit well with the estimated date of colonization of Australia based on archeological evidence (~47 000 years ago). The distribution of mtDNA haplogroups in Australia and New Guinea supports the hypothesis that the ancestors of Aboriginal Australians entered Sahul through at least two entry points. The mtDNA data give no support to the hypothesis of secondary gene flow into Australia during the Holocene, but instead suggest long-term isolation of the continent.

  18. Acid sulphate soil disturbance and metals in groundwater: Implications for human exposure through home grown produce

    International Nuclear Information System (INIS)

    Hinwood, Andrea Lee; Horwitz, Pierre; Appleyard, Steve; Barton, Caroline; Wajrak, Magda

    2006-01-01

    A significant emerging environmental problem is the disturbance and oxidation of soils with high levels of iron sulphide minerals resulting in acidification and causing the mobilization of metals into groundwater. This process is occurring in many parts of the world. In Western Australia, impacted groundwater is extracted by residents for domestic use. We sought to establish domestic use patterns of bore water and the concentration of metals. Sixty-seven domestic bore water samples clearly indicated oxidation of sulphidic materials with heavy metal concentrations ranging for aluminium (< DL-37.0 mg/L), arsenic (< DL-6.6 mg/L), iron (< DL-1200 mg/L), cadmium (< DL-0.021 mg/L), lead (< DL-0.040 mg/L), selenium (< DL-0.006 mg/L). A high proportion of residents used bore water on home grown produce. The study suggests that there is potential for human exposure to heavy metals via the consumption of home grown produce. This warrants further investigation in light of increasing acid sulphate soil disturbance in many locations. - Acidified bore water may introduce metals into produce for home consumption

  19. Factors involved in depletion of glutathione from A549 human lung carcinoma cells: implications for radiotherapy

    International Nuclear Information System (INIS)

    Biaglow, J.E.; Varnes, M.E.; Epp, E.R.; Clark, E.P.

    1984-01-01

    The rate of GSH resynthesis has been measured in plateau phase cultures of A549 human lung carcinoma cells subjected to a fresh medium change. Buthionine sulfoximine (BSO) blocks this resynthesis. Diethyl maleate (DEM) causes a decrease in accumulation of GSH. If DEM is added concurrently with BSO there is a rapid decline in GSH that is maximal in the presence of 0.5 mM DEM. GSH depletion rapidly occurs when BSO is added to log phase cultures which initially are higher in GSH content. Twenty-four hr treatment of A549 cells with BSO results in cells that are more radiosensitive in air and show a slight hypoxic radiation response. A 2 hr treatment with DEM results in some hypoxic sensitization and little increase in the aerobic radiation response. Cells treated simultaneously with BSO + DEM show little increase in the hypoxic radiation response, compared to DEM alone, but are more sensitive under aerobic conditions. Decreased cell survival for aerobically irradiated log phase A549 cells occurs within minutes after addition of a mixture of BSO + DEM. The authors suggest that the enhanced aerobic radiation response is related to an inability of GSH depleted cells to inactivate either peroxy radicals or hydroperoxides that may be produced during irradiation of BSO treated cells. Furthermore, enhancement of the aerobic radiation response may be useful in vivo if normal tissue responses are not also increased

  20. Somatomedin A in human serum: determined by radioimmunoassay and radioreceptorassay; results and implications

    International Nuclear Information System (INIS)

    Hall, K.; Sara, V.

    1981-01-01

    The polypeptide hormones in the somatomedin family were discovered as three different biological activities of serum: insulin-like activity (ILA), sulphation factor activity (SFA) and multiplication stimulatory activity (MSA). Three different biological actions on three different target tissues have been used to identify the somatomedins during their purification. All the somatomedins contain ILA, SFA and MSA but their order of potency of biological action varies from tissue to tissue. It is apparent that the pattern of somatomedin levels determined throughout human life varies according to the technique used for their determination. Each assay has a unqiue order of crossreaction for the various somatomedins, and is sensitive to different forms present in blood. Thus the different patterns must reflect the predominance of specific somatomedins at certain stages of life. The heterogeneity of polypeptide hormones in the circulating blood is well recognized but its relation to age and development has yet to be fully explored. Methods for the estimation of the somatomedins must take account of such differences. In the radioimmunoassay field it is generally recognized that each type of antibody has a unique recognition pattern. This applies equally to the radioreceptorassay where the specificity of the receptor varies according to species, organ and age. Consequently, it is essential that age-related standards are established for each technique for the determination of somatomedins. (Auth.)

  1. Cumulative Human Impacts on Coral Reefs: Assessing Risk and Management Implications for Brazilian Coral Reefs

    Directory of Open Access Journals (Sweden)

    Rafael A. Magris

    2018-04-01

    Full Text Available Effective management of coral reefs requires strategies tailored to cope with cumulative disturbances from human activities. In Brazil, where coral reefs are a priority for conservation, intensifying threats from local and global stressors are of paramount concern to management agencies. Using a cumulative impact assessment approach, our goal was to inform management actions for coral reefs in Brazil by assessing their exposure to multiple stressors (fishing, land-based activities, coastal development, mining, aquaculture, shipping, and global warming. We calculated an index of the risk to cumulative impacts: (i assuming uniform sensitivity of coral reefs to stressors; and (ii using impact weights to reflect varying tolerance levels of coral reefs to each stressor. We also predicted the index in both the presence and absence of global warming. We found that 16% and 37% of coral reefs had high to very high risk of cumulative impacts, without and with information on sensitivity respectively, and 42% of reefs had low risk to cumulative impacts from both local and global stressors. Our outputs are the first comprehensive spatial dataset of cumulative impact on coral reefs in Brazil, and show that areas requiring attention mostly corresponded to those closer to population centres. We demonstrate how the relationships between risks from local and global stressors can be used to derive strategic management actions.

  2. Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions

    Science.gov (United States)

    Bunney, Tom D.; Cole, Ambrose R.; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W.; Katan, Matilda

    2014-01-01

    Summary Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition. PMID:25435325

  3. Antibiotic Pollution in Marine Food Webs in Laizhou Bay, North China: Trophodynamics and Human Exposure Implication.

    Science.gov (United States)

    Liu, Sisi; Zhao, Hongxia; Lehmler, Hans-Joachim; Cai, Xiyun; Chen, Jingwen

    2017-02-21

    Little information is available about the bioaccumulation and biomagnification of antibiotics in marine food webs. Here, we investigate the levels and trophic transfer of 9 sulfonamide (SA), 5 fluoroquinolone (FQ), and 4 macrolide (ML) antibiotics, as well as trimethoprim in nine invertebrate and ten fish species collected from a marine food web in Laizhou Bay, North China in 2014 and 2015. All the antibiotics were detected in the marine organisms, with SAs and FQs being the most abundant antibiotics. Benthic fish accumulated more SAs than invertebrates and pelagic fish, while invertebrates exhibited higher FQ levels than fish. Generally, SAs and trimethoprim biomagnified in the food web, while the FQs and MLs were biodiluted. Trophic magnification factors (TMF) were 1.2-3.9 for SAs and trimethoprim, 0.3-1.0 for FQs and MLs. Limited biotransformation and relatively high assimilation efficiencies are the likely reasons for the biomagnification of SAs. The pH dependent distribution coefficients (log D) but not the lipophilicity (log K OW ) of SAs and FQs had a significant correlation (r = 0.73; p < 0.05) with their TMFs. Although the calculated estimated daily intakes (EDI) for antibiotics suggest that consumption of seafood from Laizhou Bay is not associated with significant human health risks, this study provides important insights into the guidance of risk management of antibiotics.

  4. 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

  5. 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.

  6. Controversies surrounding human papilloma virus infection, head & neck vs oral cancer, implications for prophylaxis and treatment.

    Science.gov (United States)

    Campisi, Giuseppina; Giovannelli, Lucia

    2009-03-30

    Head & Neck Cancer (HNC) represents the sixth most common malignancy worldwide and it is historically linked to well-known behavioural risk factors, i.e., tobacco smoking and/or the alcohol consumption. Recently, substantial evidence has been mounting that Human Papillomavirus (HPV) infection is playing an increasing important role in oral cancer. Because of the attention and clamor surrounding oral HPV infection and related cancers, as well as the use of HPV prophylactic vaccines, in this invited perspective the authors raise some questions and review some controversial issues on HPV infection and its role in HNC, with a particular focus on oral squamous cell carcinoma. The problematic definition and classification of HNC will be discussed, together with the characteristics of oral infection with oncogenic HPV types, the frequency of HPV DNA detection in HNC, the location of HPV-related tumours, the severity and prognosis of HPV-positive HNC, the diagnosis of oral HPV infection, common routes of oral infection and the likelihood of oro-genital HPV transmission, the prevention of HPV infection and novel therapeutic approaches.

  7. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Quantifying human decomposition in an indoor setting and implications for postmortem interval estimation.

    Science.gov (United States)

    Ceciliason, Ann-Sofie; Andersson, M Gunnar; Lindström, Anders; Sandler, Håkan

    2018-02-01

    This study's objective is to obtain accuracy and precision in estimating the postmortem interval (PMI) for decomposing human remains discovered in indoor settings. Data were collected prospectively from 140 forensic cases with a known date of death, scored according to the Total Body Score (TBS) scale at the post-mortem examination. In our model setting, it is estimated that, in cases with or without the presence of blowfly larvae, approximately 45% or 66% respectively, of the variance in TBS can be derived from Accumulated Degree-Days (ADD). The precision in estimating ADD/PMI from TBS is, in our setting, moderate to low. However, dividing the cases into defined subgroups suggests the possibility to increase the precision of the model. Our findings also suggest a significant seasonal difference with concomitant influence on TBS in the complete data set, possibly initiated by the presence of insect activity mainly during summer. PMI may be underestimated in cases with presence of desiccation. Likewise, there is a need for evaluating the effect of insect activity, to avoid overestimating the PMI. Our data sample indicates that the scoring method might need to be slightly modified to better reflect indoor decomposition, especially in cases with insect infestations or/and extensive desiccation. When applying TBS in an indoor setting, the model requires distinct inclusion criteria and a defined population. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Parallel routes of human carcinoma development: implications of the age-specific incidence data.

    Directory of Open Access Journals (Sweden)

    James P Brody

    Full Text Available BACKGROUND: The multi-stage hypothesis suggests that cancers develop through a single defined series of genetic alterations. This hypothesis was first suggested over 50 years ago based upon age-specific incidence data. However, recent molecular studies of tumors indicate that multiple routes exist to the formation of cancer, not a single route. This parallel route hypothesis has not been tested with age-specific incidence data. METHODOLOGY/PRINCIPAL FINDINGS: To test the parallel route hypothesis, I formulated it in terms of a mathematical equation and then tested whether this equation was consistent with age-specific incidence data compiled by the Surveillance Epidemiology and End Results (SEER cancer registries since 1973. I used the chi-squared goodness of fit test to measure consistency. The age-specific incidence data from most human carcinomas, including those of the colon, lung, prostate, and breast were consistent with the parallel route hypothesis. However, this hypothesis is only consistent if an immune sub-population exists, one that will never develop carcinoma. Furthermore, breast carcinoma has two distinct forms of the disease, and one of these occurs at significantly different rates in different racial groups. CONCLUSIONS/SIGNIFICANCE: I conclude that the parallel route hypothesis is consistent with the age-specific incidence data only if carcinoma occurs in a distinct sub population, while the multi-stage hypothesis is inconsistent with this data.

  10. 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.

  11. [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.

  12. Endoplasmic reticulum stress disrupts placental morphogenesis: implications for human intrauterine growth restriction.

    Science.gov (United States)

    Yung, Hong Wa; Hemberger, Myriam; Watson, Erica D; Senner, Claire E; Jones, Carolyn P; Kaufman, Randal J; Charnock-Jones, D Stephen; Burton, Graham J

    2012-12-01

    We recently reported the first evidence of placental endoplasmic reticulum (ER) stress in the pathophysiology of human intrauterine growth restriction. Here, we used a mouse model to investigate potential underlying mechanisms. Eif2s1(tm1RjK) mice, in which Ser51 of eukaryotic initiation factor 2 subunit alpha (eIF2α) is mutated, display a 30% increase in basal translation. In Eif2s1(tm1RjK) placentas, we observed increased ER stress and anomalous accumulation of glycoproteins in the endocrine junctional zone (Jz), but not in the labyrinthine zone where physiological exchange occurs. Placental and fetal weights were reduced by 15% (97 mg to 82 mg, p growth factor for placental development; indeed, activity in the Pdk1-Akt-mTOR pathways was decreased in Eif2s1(tm1RjK) placentas, indicating loss of Igf2 signalling. Furthermore, we observed premature differentiation of trophoblast progenitors at E9.5 in mutant placentas, consistent with the in vitro results and with the disproportionate development of the labyrinth and Jz seen in placentas at E18.5. Similar disproportion has been reported in the Igf2-null mouse. These results demonstrate that ER stress adversely affects placental development, and that modulation of post-translational processing, and hence bioactivity, of secreted growth factors contributes to this effect. Placental dysmorphogenesis potentially affects fetal growth through reduced exchange capacity. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent

    International Nuclear Information System (INIS)

    Altomare, Deborah A; Rybak, Susanna M; Pei, Jianming; Maizel, Jacob V; Cheung, Mitchell; Testa, Joseph R; Shogen, Kuslima

    2010-01-01

    Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action. In this study, microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 μg/ml Onconase for 24 h. A total of 155 genes were found to be regulated by Onconase that were common to both epithelial and biphasic MM cell lines. Some of these genes are known to significantly affect apoptosis (IL-24, TNFAIP3), transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1) or inflammation and the immune response (IL-6, COX-2). RT-PCR analysis of selected up- or down-regulated genes treated with varying doses and times of Onconase generally confirmed the expression array findings in four MM cell lines. Onconase treatment consistently resulted in up-regulation of IL-24, previously shown to have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive MM cell lines, as defined by DNA fragmentation analysis. In addition to apoptosis, gene ontology analysis indicated that pathways impacted by Onconase include MAPK signaling, cytokine-cytokine-receptor interactions, and Jak-STAT signaling. These results provide a broad picture of gene activity after treatment with a drug that targets small non-coding RNAs and contribute to our overall understanding of MM cell response to Onconase as a therapeutic strategy. The findings provide insights regarding mechanisms that may contribute to the efficacy of this novel drug in clinical trials of MM patients who have failed first line chemotherapy or radiation treatment

  14. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

    2010-01-01

    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 ( 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 ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼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 ( 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.

  15. 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.

  16. Gendered risk perceptions associated with human-wildlife conflict: implications for participatory conservation.

    Science.gov (United States)

    Gore, Meredith L; Kahler, Jessica S

    2012-01-01

    This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1) gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC) in a participatory conservation context, and (2) highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2) to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38) to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting) dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities.

  17. Gendered risk perceptions associated with human-wildlife conflict: implications for participatory conservation.

    Directory of Open Access Journals (Sweden)

    Meredith L Gore

    Full Text Available This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1 gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC in a participatory conservation context, and (2 highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2 to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38 to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities.

  18. Role of EG-VEGF in human placentation: Physiological and pathological implications.

    Science.gov (United States)

    Hoffmann, Pascale; Saoudi, Yasmina; Benharouga, Mohamed; Graham, Charles H; Schaal, Jean-Patrick; Mazouni, Chafika; Feige, Jean-Jacques; Alfaidy, Nadia

    2009-08-01

    Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR-8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG-VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP-9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF circulating levels in normal and PE patients. Our results showed that EG-VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non-pregnant levels. More important, EG-VEGF levels were significantly elevated in PE patients compared with age-matched controls. These findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down-regulate placental expression of EG-VEGF at the end of the first trimester of pregnancy might lead to PE.

  19. Human papillomavirus genotype distribution in cervical cancer cases in Spain. Implications for prevention.

    Science.gov (United States)

    Alemany, Laia; Pérez, Cristina; Tous, Sara; Llombart-Bosch, Antonio; Lloveras, Belen; Lerma, Enrique; Guarch, Rosa; Andújar, Miguel; Pelayo, Adela; Alejo, Maria; Ordi, Jaume; Klaustermeier, Joellen; Velasco, Julio; Guimerà, Nuria; Clavero, Omar; Castellsagué, Xavier; Quint, Wim; Muñoz, Nubia; Bosch, F Xavier; de Sanjosé, Silvia

    2012-03-01

    Human papillomavirus (HPV) genotype distribution in invasive cervical cancer (ICC) is critical to guide the introduction and to assess the impact of HPV prophylactic vaccines. This study aims to provide specific information for Spain. 1043 histological confirmed ICC cases diagnosed from 1940 to 2007 from six Spanish regions were assembled. HPV DNA detection was performed by SPF(10) broad-spectrum PCR followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA(25)) (version 1). Of 1043 ICC cases, 904 were HPV DNA positive (adjusted prevalence: 89.1%). The eight most common types, in decreasing order, were HPV 16, 18, 33, 31, 45, 35, 52 and 56, accounting for more than 90% of cases. HPV 16 and 18 contributed to 72.4% of all HPV positive ICC cases. In cervical adenocarcinomas, this contribution increased up to 94%. HPV 16 and 18 relative contributions showed a stable pattern over the 60 year study period. HPV 45, 18 and 16-positive ICC cases presented at younger ages than cases with other HPV types (adjusted mean age: 43.8, 45.2, 52.6 and 57.7 years, respectively). HPV 16 and 18 accounted together for a 72.4% of positive cases, with no statistically significant changes in their relative contributions over the last decades. In 94% of cervical adenocarcinomas we identified at least one of the two HPV types included in the current vaccines (HPV 16/18). Results suggest a major impact of HPV vaccines on reduction of ICC burden in Spain in the HPV vaccinated cohorts. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. 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.

  1. Implications of climate change on human comfort in buildings: evidence from Nkontompo community of Sekondi-Takoradi, Ghana

    Energy Technology Data Exchange (ETDEWEB)

    Amos-Abanyie, S. [Kwame Nkrumah Univ. of Science and Technology, Kumasi (GH)

    2006-07-01

    Climate change has become the most talked about issue in recent times. The impact of climate change is likely to become more evident in the coming decades. Currently, atmospheric conditions, especially in the dry season, are getting hotter and drier with increased heat waves. Increased demand for air conditioning for space cooling as a result of internal discomfort in buildings is already manifesting. This could put an additional stress on the already over-burdened energy capactiy of the nation. The study on implications of climate change on human comfort in buidlings was conducted in Nkontompo community, a suburb of Sekondi-Takoradi Metropolitan area of the Shama-Ahanta District of the Western Region of Ghana. The objectives of this study are to assemble and disseminate information about some of the possible impacts of climate change on the built environment. This is to set the platform for building professionals to identify possible adaptive measures to serve as basis for development of standards to maintain and enhance the quality of life in buildings. The results showed that there were significant changes in temperature, precipitation, and relative humidity. A rise in temperature and humidity levels constitutes a potential hazard to health and human comfort and accelerates many degradation processes and material damage. Subsequently, the amount of energy needed to maintain the condition of air in spaces at comfort levels keeps increasing. It is therefore imperative that landlords and other property owners should be effectively guided by qualified professionals within the framework of policy guidelines based on sound research.

  2. 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.

  3. Health risk assessment of heavy metals in wheat using different water qualities: implication for human health.

    Science.gov (United States)

    Khan, Zafar Iqbal; Ahmad, Kafeel; Rehman, Sidrah; Siddique, Samra; Bashir, Humayun; Zafar, Asma; Sohail, Muhammad; Ali, Salem Alhajj; Cazzato, Eugenio; De Mastro, Giuseppe

    2017-01-01

    In the recent years, the use of sewage water for irrigation has attracted the attention of arid and semi-arid countries where the availability of fresh water is poor. Despite the potential use of sewage water in crop irrigation as effective and sustainable strategy, the environmental and human risks behind this use need to be deeply investigated. In this regard, an experiment was carried out under field conditions in Nursery, University College of Agriculture Sargodha, to evaluate the possible health risks of undesirable metals in wheat grains. Wheat variety Sarang was cultivated and irrigated with different combinations of ground (GW) and sewage water (SW). The concentrations of heavy metals (Cr, Cd, Ni, and Pb) and trace elements (Cu, Zn, and Fe) in wheat grains as well as in soil were determined. Moreover, the pollution load index (PLI), accumulation factor (AF), daily intake of metals (DIM), and health risk index (HRI) were calculated. Results showed that the concentration trend of heavy metals was Pbmetals, Cd concentration in wheat exceeded the permissible limits regardless water quality, whereas Pb concentration in grain was within the acceptable levels as suggested by World Health Organization, when 100 % of SW was used for irrigation. Similar observation was reported for Cd concentration in the soil when wheat was irrigated with 100 % SW. In comparison to soil, the edible part of wheat presented lower concentration of all studied metals, except for Zn which was much higher compared to the tested soil samples. The higher concentration of Zn was responsible for increasing the DIM of Zn where, in average, the highest value was reported, particularly in 75 % SW treatment. This was reflected also in HRI where the maximum value was reported for Zinc under the same treatment. Higher value of HRI for wheat cultivated on polluted soils suggested that appropriate management of cultivated area is necessary for food safety and thus for public health. The results

  4. Zoonotic gastrointestinal parasite burden of local dogs in Zaria, Northern Nigeria: Implications for human health

    Directory of Open Access Journals (Sweden)

    Christopher I. Ogbaje

    2015-10-01

    Full Text Available Background: Zoonotic gastrointestinal parasites of dogs are of the global problem particularly in the developing countries. Dogs are the most common pet animals worldwide and have been reported to be hosts of many intestinal parasites of zoonotic importance globally. In Nigeria, gastrointestinal helminthes of dogs is currently endemic in 20 of the 36 states. Aim: In general, dogs are the closest animals to humans and for that reason we decided to carry out a survey study to check the incidence of these parasites in dogs and to ascertain the level of environmental contamination in the study area. Materials and Methods: Fecal samples were collected from dog patients presented to small animal clinic of Veterinary Teaching Hospital of Faculty of Veterinary Medicine, Ahmadu Bello University Zaria, dog’s fecal droppings from the streets, and residential Quarters of the University and gastrointestinal tracts (GIT of dogs from dogs slaughtering house at Basawa Barrack, Zaria. Three methods were used in the analysis of the samples; simple flotation, sedimentation, and GIT processing methods within 48 h of collection. Results: Out of 224 samples analyzed 76(33.9% were positive of at least one of the parasites. Of the 101 samples from streets and residential quarters of ABU, Zaria, Isospora spp. 12(11.9% recorded the highest prevalence rate followed by Taenia spp. 6(5.9%, then Toxocara canis, Ancylostoma caninum, and Dipylidium caninum were 5.0%, 4.0%, and 1.0%, respectively. Isospora spp. (19.0% recorded the highest prevalence rate for the 100 samples collected from small animal clinic. Other parasites encountered were T. canis (8.0%, A. caninum (8.0% and Taenia spp. (5.0%. Parasites observed from the 23 gastrointestinal contents from “dog slaughtered houses” were T. canis (17.3%, Isospora spp.(13.1% and A. caninum (4.3. Conclusion: The study revealed that zoonotic gastrointestinal parasites of dogs are endemic in Zaria and the general public in the

  5. Brominated flame retardants in black plastic kitchen utensils: Concentrations and human exposure implications.

    Science.gov (United States)

    Kuang, Jiangmeng; Abdallah, Mohamed Abou-Elwafa; Harrad, Stuart

    2018-01-01

    Concerns exist that restricted brominated flame retardants (BFRs) present in waste polymers may have, as a result of recycling, inadvertently contaminated items not required to meet flame retardancy regulations (e.g. plastic kitchen utensils). To investigate the extent to which kitchen utensils are contaminated with BFRs and the potential for resultant human exposure, we collected 96 plastic kitchen utensils and screened for Br content using a hand-held X-ray fluorescence (XRF) spectrometer. Only 3 out of 27 utensils purchased after 2011 contained detectable concentrations of Br (≥3μg/g). In contrast, Br was detected in 31 out of the 69 utensils purchased before 2011. Eighteen utensils with Br content higher than 100μg/g, and 12 new utensils were selected for GC-MS analysis of BFRs. BFRs targeted were polybrominated diphenyl ethers (PBDEs) BDE-28, 47, 99, 100, 153, 154, 183 and 209, and novel BFRs (NBFRs) pentabromoethylbenzene (PBEB), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (BEH-TEBP) and decabromodiphenyl ethane (DBDPE). The ability of XRF to act as a surrogate metric of BFR concentration was indicated by a significant (Spearman coefficient=0.493; p=0.006) positive relationship between Br and ΣBFR concentration. Measurements of ΣBFRs were always exceeded by those of Br. This may be due partly to the presence of BFRs not targeted in our study and also to reduced extraction efficiency of BFRs from utensils. Of our target BFRs, BDE-209 was the most abundant one in most samples, but an extremely high concentration (1000μg/g) of BTBPE was found in one utensil. Simulated cooking experiments were conducted to investigate BFR transfer from selected utensils (n=10) to hot cooking oil, with considerable transfer (20% on average) observed. Estimated median exposure via cooking with BFR contaminated utensils was 60ng/day for total BFRs. In contrast, estimated

  6. Morphine induces expression of platelet-derived growth factor in human brain microvascular endothelial cells: implication for vascular permeability.

    Directory of Open Access Journals (Sweden)

    Hongxiu Wen

    Full Text Available Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Morphine, often abused by HIV-infected patients, is known to accelerate neuroinflammation associated with HIV-1 infection. Detailed molecular mechanisms of morphine action however, remain poorly understood. Platelet-derived growth factor (PDGF has been implicated in a number of pathological conditions, primarily due to its potent mitogenic and permeability effects. Whether morphine exposure results in enhanced vascular permeability in brain endothelial cells, likely via induction of PDGF, remains to be established. In the present study, we demonstrated morphine-mediated induction of PDGF-BB in human brain microvascular endothelial cells, an effect that was abrogated by the opioid receptor antagonist-naltrexone. Pharmacological blockade (cell signaling and loss-of-function (Egr-1 approaches demonstrated the role of mitogen-activated protein kinases (MAPKs, PI3K/Akt and the downstream transcription factor Egr-1 respectively, in morphine-mediated induction of PDGF-BB. Functional significance of increased PDGF-BB manifested as increased breach of the endothelial barrier as evidenced by decreased expression of the tight junction protein ZO-1 in an in vitro model system. Understanding the regulation of PDGF expression may provide insights into the development of potential therapeutic targets for intervention of morphine-mediated neuroinflammation.

  7. 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.

  8. Fate of Chloromethanes in the Atmospheric Environment: Implications for Human Health, Ozone Formation and Depletion, and Global Warming Impacts.

    Science.gov (United States)

    Tsai, Wen-Tien

    2017-09-21

    Among the halogenated hydrocarbons, chloromethanes (i.e., methyl chloride, CH₃Cl; methylene chloride, CH₂Cl₂; chloroform, CHCl₃; and carbon tetrachloride, CCl₄) play a vital role due to their extensive uses as solvents and chemical intermediates. This article aims to review their main chemical/physical properties and commercial/industrial uses, as well as the environment and health hazards posed by them and their toxic decomposition products. The environmental properties (including atmospheric lifetime, radiative efficiency, ozone depletion potential, global warming potential, photochemical ozone creation potential, and surface mixing ratio) of these chlorinated methanes are also reviewed. In addition, this paper further discusses their atmospheric fates and human health implications because they are apt to reside in the lower atmosphere when released into the environment. According to the atmospheric degradation mechanism, their toxic degradation products in the troposphere include hydrogen chloride (HCl), carbon monoxide (CO), chlorine (Cl₂), formyl chloride (HCOCl), carbonyl chloride (COCl₂), and hydrogen peroxide (H₂O₂). Among them, COCl₂ (also called phosgene) is a powerful irritating gas, which is easily hydrolyzed or thermally decomposed to form hydrogen chloride.

  9. Fate of Chloromethanes in the Atmospheric Environment: Implications for Human Health, Ozone Formation and Depletion, and Global Warming Impacts

    Science.gov (United States)

    Tsai, Wen-Tien

    2017-01-01

    Among the halogenated hydrocarbons, chloromethanes (i.e., methyl chloride, CH3Cl; methylene chloride, CH2Cl2; chloroform, CHCl3; and carbon tetrachloride, CCl4) play a vital role due to their extensive uses as solvents and chemical intermediates. This article aims to review their main chemical/physical properties and commercial/industrial uses, as well as the environment and health hazards posed by them and their toxic decomposition products. The environmental properties (including atmospheric lifetime, radiative efficiency, ozone depletion potential, global warming potential, photochemical ozone creation potential, and surface mixing ratio) of these chlorinated methanes are also reviewed. In addition, this paper further discusses their atmospheric fates and human health implications because they are apt to reside in the lower atmosphere when released into the environment. According to the atmospheric degradation mechanism, their toxic degradation products in the troposphere include hydrogen chloride (HCl), carbon monoxide (CO), chlorine (Cl2), formyl chloride (HCOCl), carbonyl chloride (COCl2), and hydrogen peroxide (H2O2). Among them, COCl2 (also called phosgene) is a powerful irritating gas, which is easily hydrolyzed or thermally decomposed to form hydrogen chloride. PMID:29051455

  10. Sperm donation: implications of Canada's Assisted Human Reproduction Act 2004 for recipients, donors, health professionals, and institutions.

    Science.gov (United States)

    Daniels, K; Feyles, V; Nisker, J; Perez-Y-Perez, M; Newton, C; Parker, J A; Tekpetey, F; Haase, J

    2006-07-01

    On April 22, 2004, the Assisted Human Reproduction Act came into force, prohibiting the purchase of sperm or eggs from donors in Canada. In response to the concerns of medical professionals and some consumers that prohibiting payment would lead to a decline in the number of gamete donors, Health Canada commissioned research on altruistic donor recruitment and recruitment strategies. Twenty-two studies of sperm donors were located and their findings reviewed. The studies spanned 23 years (1980-2003), were undertaken in a range of countries, and were chosen on the merit of their relevance to the development of recruitment strategies within a policy of altruistic sperm donation. Observations were derived from assessing and comparing the purposes, findings, and implications of the 22 studies. Payment for providing sperm was made in all but three studies, although participants in 15 studies indicated clearly that their motivations were primarily altruistic. Observations indicate that men who are more willing to be identified to offspring in the future share demographic characteristics, such as age and parental status, with those who are prepared to donate altruistically. These characteristics appear to be a factor in motivation to donate altruistically. The studies show that there are men who are prepared to donate sperm without financial payment. The findings suggest that a change is required in the culture of sperm donation, specifically the adoption of a new approach to donor recruitment.

  11. A study of particulate emissions during 23 major industrial fires: Implications for human health.

    Science.gov (United States)

    Griffiths, Simon D; Chappell, Philip; Entwistle, Jane A; Kelly, Frank J; Deary, Michael E

    2018-03-01

    Public exposure to significantly elevated levels of particulate matter (PM) as a result of major fires at industrial sites is a worldwide problem. Our paper describes how the United Kingdom developed its Air Quality in Major Incidents (AQinMI) service to provide fire emission plume concentration data for use by managers at the time of the incident and to allow an informed public health response. It is one of the first civilian services of its type anywhere in the world. Based on the involvement of several of the authors in the AQinMI service, we describe the service's function, detail the nature of fires covered by the service, and report for the first time on the concentration ranges of PM to which populations may be exposed in major incident fires. We also consider the human health impacts of short-term exposure to significantly elevated PM concentrations and reflect on the appropriateness of current short-term guideline values in providing public health advice. We have analysed monitoring data for airborne PM (≤10μm, PM 10 ;≤2.5μm, PM 2.5 and ≤1.0μm, PM 1 ) collected by AQinMI teams using an Osiris laser light scattering monitor, the UK Environment Agency's 'indicative standard' equipment, during deployment to 23 major incident industrial fires. In this context, 'indicative' is applied to monitoring equipment that provides confirmation of the presence of particulates and indicates a measured mass concentration value. Incident-averaged concentrations ranged from 38 to 1450μgm -3 for PM 10 and 7 to 258μgm -3 for PM 2.5 . Of concern was that, for several incidents, 15-min averaged concentrations reached >6500μgm -3 for PM 10 and 650μgm -3 for PM 2.5 , though such excursions tended to be of relatively short duration. In the absence of accepted very short-term (15-min to 1-h) guideline values for PM 10 and PM 2.5, we have analysed the relationship between the 1-h and 24-h threshold values and whether the former can be used as a predictor of longer

  12. Perceptions of human papillomavirus vaccination of adolescent schoolgirls in western Uganda and their implications for acceptability of HPV vaccination: a qualitative study

    OpenAIRE

    Turiho, Andrew Kampikaho; Okello, Elialilia Sarikieli; Muhwezi, Wilson Winstons; Katahoire, Anne Ruhweza

    2017-01-01

    Background Human papillomavirus (HPV) vaccination has been perceived in diverse ways some of which encourage its uptake while others could potentially deter its acceptability. This study explored community member?s perceptions about HPV vaccination in Ibanda district and the implications of the perceptions for acceptability of HPV vaccination. The study was conducted following initial vaccination of adolescent schoolgirls in the district between 2008 and 2011. Methods This qualitative study e...

  13. Projections of 21st Century African Climate: Implications for African Savanna Fire Dynamics, Human Health and Food Security

    Science.gov (United States)

    Adegoke, J. O.

    2015-12-01

    Fire is a key agent of change in the African savannas, which are shaped through the complex interactions between trees, C4 grasses, rainfall, temperature, CO2 and fire. These fires and their emitted smoke can have numerous direct and indirect effects on the environment, water resources, air quality, and climate. For instance, veld fires in southern Africa cause large financial losses to agriculture, livestock production and forestry on an annual basis. This study contributes to our understanding of the implications of projected surface temperature evolution in Africa for fire risk, human health and agriculture over the coming decades. We use an ensemble of high-resolution regional climate model simulations of African climate for the 21st century. Regional dowscalings and recent global circulation model projections obtained for Africa indicate that African temperatures are likely to rise at 1.5 times the global rate of temperature increase in the tropics, and at almost twice the global rate of increase in the subtropics. Warming is projected to occur during the 21st century, with increases of 4-6 °C over the subtropics and 3-5 °C over the tropics plausible by the end of the century relative to present-day climate under the A2 (low mitigation) scenario. We explore the significance of the projected warming by documenting increases in projected high fire danger days and heat-wave days. General drying is projected across the continent, even for areas (e.g. tropical Africa) where an increase in rainfall is plausible. This is due to the drastic increases in temperature that are projected, which leads to drier soils (through enhanced evaporation) despite the rainfall increases. This will likely impact negatively on crop yield, particularly on the maize crop that is of crucial importance in terms of African food security.

  14. The connection between human papillomavirus and oropharyngeal squamous cell carcinomas in the United States: implications for dentistry.

    Science.gov (United States)

    Cleveland, Jennifer L; Junger, Michele L; Saraiya, Mona; Markowitz, Lauri E; Dunne, Eileen F; Epstein, Joel B

    2011-08-01

    Results from studies conducted in the past several years suggest that some oropharyngeal cancers, those of the base of the tongue and the tonsils, are associated with high-risk types of human papillomavirus (HPV). In this article, the authors summarize the available evidence regarding the epidemiology of HPV-associated oropharyngeal cancers in the United States, the available HPV vaccines and the implications of these for dentistry. They also examine the differences in HPV prevalence between cancers of the oral cavity and those of the oropharynx. The authors searched PubMed, Web of Science, The Cochrane Library and the National Guideline Clearinghouse to identify English-language systematic reviews and meta-analyses focused on HPV-associated oropharyngeal squamous cell cancers published from January 2005 through May 2011. Molecular and epidemiologic evidence suggest a strong etiologic association of HPV with oropharyngeal cancers. The incidence of oropharyngeal cancers in the United States has increased between 1973 and 2007, whereas that of cancers at other head and neck sites has decreased steadily. Compared with HPV-negative cancers, HPV-positive oropharyngeal cancers are associated with certain sexual behaviors, occur more often among white men and people who do not use tobacco or alcohol, and may occur in a population younger by about four years (median ages, 52-56 years). Despite often having a later stage of diagnosis, people with HPV-positive oropharyngeal cancers have a lower risk of dying or recurrence than do those with HPV-negative cancers. The effectiveness of the HPV vaccine in preventing oropharyngeal cancers is unknown. Dental health care personnel (DHCP) should be knowledgeable about the role of HPV in carcinogenesis, the association of HPV with oropharyngeal cancers and HPV vaccines, and they should be prompt in referring patients with suggestive symptoms for evaluation. DHCP can play an important role in increasing patients' knowledge about HPV

  15. Forensic human identification in the United States and Canada: a review of the law, admissible techniques, and the legal implications of their application in forensic cases.

    Science.gov (United States)

    Holobinko, Anastasia

    2012-10-10

    Forensic human identification techniques are successful if they lead to positive personal identification. However, the strongest personal identification is of no use in the prosecution--or vindication--of an accused if the associated evidence and testimony is ruled inadmissible in a court of law. This review examines the U.S. and Canadian legal rulings regarding the admissibility of expert evidence and testimony, and subsequently explores four established methods of human identification (i.e., DNA profiling, forensic anthropology, forensic radiography, forensic odontology) and one complementary technique useful in determining identity, and the legal implications of their application in forensic cases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Konopka, James B

    2016-03-01

    Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans.

  17. Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans

    Science.gov (United States)

    Douglas, Lois M.; Konopka, James. B.

    2017-01-01

    Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans. PMID:26920878

  18. Airway basement membrane perimeter in human airways is not a constant; potential implications for airway remodeling in asthma.

    Science.gov (United States)

    McParland, Brent E; Paré, Peter D; Johnson, Peter R A; Armour, Carol L; Black, Judith L

    2004-08-01

    Many studies that demonstrate an increase in airway smooth muscle in asthmatic patients rely on the assumption that bronchial internal perimeter (P(i)) or basement membrane perimeter (P(bm)) is a constant, i.e., not affected by fixation pressure or the degree of smooth muscle shortening. Because it is the basement membrane that has been purported to be the indistensible structure, this study examines the assumption that P(bm) is not affected by fixation pressure. P(bm) was determined for the same human airway segment (n = 12) fixed at distending pressures of 0 cmH(2)O and 21 cmH(2)O in the absence of smooth muscle tone. P(bm) for the segment fixed at 0 cmH(2)O was determined morphometrically, and the P(bm) for the same segment, had the segment been fixed at 21 cmH(2)O, was predicted from knowing the luminal volume and length of the airway when distended to 21 cmH(2)O (organ bath-derived P(i)). To ensure an accurate transformation of the organ bath-derived P(i) value to a morphometry-derived P(bm) value, had the segment been fixed at 21 cmH(2)O, the relationship between organ bath-derived P(i) and morphometry-derived P(bm) was determined for five different bronchial segments distended to 21 cmH(2)O and fixed at 21 cmH(2)O (r(2) = 0.99, P < 0.0001). Mean P(bm) for bronchial segments fixed at 0 cmH(2)O was 9.4 +/- 0.4 mm, whereas mean predicted P(bm), had the segments been fixed at 21 cmH(2)O, was 14.1 +/- 0.5 mm (P < 0.0001). This indicates that P(bm) is not a constant when isolated airway segments without smooth muscle tone are fixed distended to 21 cmH(2)O. The implication of these results is that the increase in smooth muscle mass in asthma may have been overestimated in some previous studies. Therefore, further studies are required to examine the potential artifact using whole lungs with and without abolition of airway smooth muscle tone and/or inflation.

  19. Gaps in college biology students' understanding of photosynthesis: Implications for human constructivist learning theory and college classroom practice

    Science.gov (United States)

    Griffard, Phyllis Baudoin

    1999-11-01

    The main research question of this study was: What gaps in biochemical understanding are revealed by a range of university introductory biology students as they work through a critically acclaimed multimedia program on photosynthesis, and what are the corresponding implications for elaboration of the Ausubel-Novak-Gowin Learning Theory (ANG, now Human Constructivism)? Twelve students, mixed for ability, gender and ethnicity, were recruited from two sections of "Bio 101." Before and after instruction in photosynthesis, in-depth clinical interviews were conducted during which participants completed a range of cognitive tasks such as sorting, concept mapping, explaining and predicting. Some tasks involved interacting with a computer simulation of photosynthesis. This study primarily employed qualitative case study and verbal analysis methods. Verbal analysis of the clinical interviews revealed numerous gaps that were categorized into typologies. The two major categories were propositional gaps and processing gaps. Propositional gaps were evident in development of participants' concepts, links and constructs. Significant among these were conceptual distance gaps and continuity of matter gaps. Gaps such as convention gaps and relative significance gaps seem to be due to naivete in the discipline. Processing gaps included gaps in graphic decoding skills and relevant cognitive habits such as self-monitoring and consulting prior knowledge. Although the gaps were easier to detect and isolate with the above-average participants, all participants showed evidence of at least some of these gaps. Since some gaps are not unexpected at all but the highest literacy levels, not all the gaps identified are to be considered deficiencies. The gaps identified support the attention given by ANG theorists to the role of prior knowledge and metacognition as well as the value of graphic organizers in knowledge construction. In addition, this study revealed numerous gaps in graphic decoding

  20. Prognostic implications of carboxyl-terminus of Hsc70 interacting protein and lysyl-oxidase expression in human breast cancer

    Directory of Open Access Journals (Sweden)

    Patani Neill

    2010-01-01

    Full Text Available Background: Ubiquitin modification of proteins influences cellular processes relevant to carcinogenesis. CHIP (carboxyl-terminus of Hsc70-interacting protein is a chaperone-dependent E3 ubiquitin ligase, regulating the stability of heat shock protein 90 (HSP90 interacting proteins. CHIP is implicated in the modulation of estrogen receptor (ESR1 and Her-2/neu (ERBB2 stability. LOX (lysyl-oxidase serves intracellular roles and catalyses the cross-linking of extracellular matrix (ECM collagens and elastin. LOX expression is altered in human malignancies and their peri-tumoral stroma. However, paradoxical roles are reported. In this study, the level of mRNA expression of CHIP and LOX were assessed in normal and malignant breast tissue and correlated with clinico-pathological parameters. Materials and Methods: Breast cancer (BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription; transcript levels were determined using real-time quantitative PCR and normalized against CK-19. Transcript levels were analyzed against TNM stage, nodal involvement, tumor grade and clinical outcome over a ten-year follow-up period. Results: CHIP expression decreased with increasing Nottingham Prognostic Index (NPI: NPI-1 vs. NPI-3 (12.2 vs. 0.2, P = 0.0264, NPI-2 vs. NPI-3 (3 vs. 0.2, P = 0.0275. CHIP expression decreased with increasing TNM stage: TNM-1 vs. TNM-2 (12 vs. 0, P = 0.0639, TNM-1 vs. TNM-2-4 (12 vs. 0, P = 0.0434. Lower transcript levels were associated with increasing tumor grade: grade 1 vs. grade 3 (17.7 vs. 0.3, P = 0.0266, grade 2 vs. grade 3 (5 vs. 0.3, P = 0.0454. The overall survival (OS for tumors classified as ′low-level expression′, was poorer than those with ′high-level expression′ (118.1 vs. 152.3 months, P = 0.039. LOX expression decreased with increasing NPI: NPI-1 vs. NPI-2 (3 vs. 0, P = 0.0301 and TNM stage: TNM-1 = 3854639, TNM-2 = 908900, TNM-3 = 329, TNM-4 = 1.232 (P = NS. Conclusion: CHIP

  1. Natural and human drivers of salinity in reservoirs and their implications in water supply operation through a Decision Support System

    Science.gov (United States)

    Contreras, Eva; Gómez-Beas, Raquel; Linares-Sáez, Antonio

    2016-04-01

    changes from 3800 to 5100 μScm-1 in the deepest layers are found with a similar daily water inflow. On the other hand, when reservoir water level is low, salinity increases around 1000 μScm-1 are found with a 2 m water level falling. In view of the influence of water level in the reservoir dynamics, this factor should be considered when dam operation decisions are taken by managers in terms of satisfying the water demand. The results will be implemented in a Decision Support System that is being displayed in the Guadalhorce River and which includes prediction of water quantity and quality in the reservoir in terms of salinity, involving water level and water inflow forecasting as the main factors to control the state of the reservoir and therefore with implications in water management. This methodology could be implemented in other reservoirs with high salinity and be adapted to other substances (such as nutrients and heavy metals) associated to water inflow in water bodies where water quality and quantity are driven by human decisions factors besides natural factors such as floods and dynamics of flows in the reservoir.

  2. Epidemiological and radio-biological studies in high background radiation areas of Kerala coast: implications in radiation protection science and human health

    International Nuclear Information System (INIS)

    Das, Birajalaxmi

    2018-01-01

    Till date, Linear No Threshold hypothesis (LNT) is well accepted in radiation protection science in spite of its limitations. However, dose response studies using multiple biological end points from high-background radiation areas have challenged the linearity. Radio-biological and epidemiological studies from high level natural radiation areas of Kerala coast showed non-linearity as well as efficient repair of DNA damage in HLNRA indicating that dose limits for public exposure needs to be revisited which may have implications in radiation protection science, human health and low dose radiation biology. However, further studies using high throughput approach is required to identify chronic radiation signatures in human population exposed to elevated level of natural background radiation

  3. High Resolution Spatial Mapping of Human Footprint across Antarctica and Its Implications for the Strategic Conservation of Avifauna

    OpenAIRE

    Peter, Hans-Ulrich; Pertierra, Luis R.; Hughes, Kevin A.; Vega, Greta C.; Olalla-Tárraga, Miguel Á.

    2017-01-01

    Human footprint models allow visualization of human spatial pressure across the globe. Up until now, Antarctica has been omitted from global footprint models, due possibly to the lack of a permanent human population and poor accessibility to necessary datasets. Yet Antarctic ecosystems face increasing cumulative impacts from the expanding tourism industry and national Antarctic operator activities, the management of which could be improved with footprint assessment tools. Moreover, Antarctic ...

  4. A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans

    DEFF Research Database (Denmark)

    Brophy, Patrick D.; Rasmussen, Maria; Parida, Mrutyunjaya

    2017-01-01

    investigations have identified several gene variants that cause RA, including EYA1, LHX1, and WT1 However, whereas compound null mutations of genes encoding α and γ retinoic acid receptors (RARs) cause RA in mice, to date there have been no reports of variants in RAR genes causing RA in humans. In this study, we...... in humans....

  5. Untangling human development and natural gradients: implications of underlying correlation structure for linking landscapes and riverine ecosystems

    Science.gov (United States)

    Yasmin Lucero; E. Ashley Steel; Kelly M. Burnett; Kelly. Christiansen

    2011-01-01

    Increasingly, ecologists seek to identify and quantify relationships between landscape gradients and aquatic ecosystems. Considerable statistical challenges emerge in this effort, some of which are attributable to multicollinearity between human development and landscape gradients. In this paper, we measure the covariation between human development—such as agriculture...

  6. An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism

    Science.gov (United States)

    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 in...

  7. Most of rare missense alleles in humans are deleterious:implications for evolution of complex disease and associationstudies

    Energy Technology Data Exchange (ETDEWEB)

    Kryukov, Gregory V.; Pennacchio, Len A.; Sunyaev, Shamil R.

    2006-10-24

    The accumulation of mildly deleterious missense mutations inindividual human genomes has been proposed to be a genetic basis forcomplex diseases. The plausibility of this hypothesis depends onquantitative estimates of the prevalence of mildly deleterious de novomutations and polymorphic variants in humans and on the intensity ofselective pressure against them. We combined analysis of mutationscausing human Mendelian diseases, human-chimpanzee divergence andsystematic data on human SNPs and found that about 20 percent of newmissense mutations in humans result in a loss of function, while about 27percent are effectively neutral. Thus, more than half of new missensemutations have mildly deleterious effects. These mutations give rise tomany low frequency deleterious allelic variants in the human populationas evident from a new dataset of 37 genes sequenced in over 1,500individual human chromosomes. Surprisingly, up to 70 percent of lowfrequency missense alleles are mildly deleterious and associated with aheterozygous fitness loss in the range 0.001-0.003. Thus, the low allelefrequency of an amino acid variant can by itself serve as a predictor ofits functional significance. Several recent studies have reported asignificant excess of rare missense variants in disease populationscompared to controls in candidate genes or pathways. These studies wouldbe unlikely to work if most rare variants were neutral or if rarevariants were not a significant contributor to the genetic component ofphenotypic inheritance. Our results provide a justification for thesetypes of candidate gene (pathway) association studies and imply thatmutation-selection balance may be a feasible mechanism for evolution ofsome common diseases.

  8. Identification of Metabolism and Excretion Differences of Procymidone between Rats and Humans Using Chimeric Mice: Implications for Differential Developmental Toxicity.

    Science.gov (United States)

    Abe, Jun; Tomigahara, Yoshitaka; Tarui, Hirokazu; Omori, Rie; Kawamura, Satoshi

    2018-02-28

    A metabolite of procymidone, hydroxylated-PCM, causes rat-specific developmental toxicity due to higher exposure to it in rats than in rabbits or monkeys. When procymidone was administered to chimeric mice with rat or human hepatocytes, the plasma level of hydroxylated-PCM was higher than that of procymidone in rat chimeric mice, and the metabolic profile of procymidone in intact rats was well reproduced in rat chimeric mice. In human chimeric mice, the plasma level of hydroxylated-PCM was less, resulting in a much lower exposure. The main excretion route of hydroxylated-PCM-glucuronide was bile (the point that hydroxylated-PCM enters the enterohepatic circulation) in rat chimeric mice, and urine in human chimeric mice. These data suggest that humans, in contrast to rats, extensively form the glucuronide and excrete it in urine, as do rabbits and monkeys. Overall, procymidone's potential for causing teratogenicity in humans must be low compared to that in rats.

  9. Brief Communication: Quantitative- and molecular-genetic differentiation in humans and chimpanzees: implications for the evolutionary processes underlying cranial diversification.

    Science.gov (United States)

    Weaver, Timothy D

    2014-08-01

    Estimates of the amount of genetic differentiation in humans among major geographic regions (e.g., Eastern Asia vs. Europe) from quantitative-genetic analyses of cranial measurements closely match those from classical- and molecular-genetic markers. Typically, among-region differences account for ∼10% of the total variation. This correspondence is generally interpreted as evidence for the importance of neutral evolutionary processes (e.g., genetic drift) in generating among-region differences in human cranial form, but it was initially surprising because human cranial diversity was frequently assumed to show a strong signature of natural selection. Is the human degree of similarity of cranial and DNA-sequence estimates of among-region genetic differentiation unusual? How do comparisons with other taxa illuminate the evolutionary processes underlying cranial diversification? Chimpanzees provide a useful starting point for placing the human results in a broader comparative context, because common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the extant species most closely related to humans. To address these questions, I used 27 cranial measurements collected on a sample of 861 humans and 263 chimpanzees to estimate the amount of genetic differentiation between pairs of groups (between regions for humans and between species or subspecies for chimpanzees). Consistent with previous results, the human cranial estimates are quite similar to published DNA-sequence estimates. In contrast, the chimpanzee cranial estimates are much smaller than published DNA-sequence estimates. It appears that cranial differentiation has been limited in chimpanzees relative to humans. © 2014 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Eric K Hoobler

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

  11. A literature review on cardiovascular risk in human immunodeficiency virus-infected patients: implications for clinical management

    Directory of Open Access Journals (Sweden)

    Mansueto Gomes Neto

    Full Text Available INTRODUCTION: In recent years, there has been growing concern about an increasing rate of cardiovascular diseases in human immunodeficiency virus-infected patients, which could be associated with side effects of highly active antiretroviral therapy. It is likely that the metabolic disorders related to anti-human immunodeficiency virus treatment will eventually translate into a increased cardiovascular risk in patients submitted to such regimens. OBJECTIVE: To evaluate if human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy are at higher risk of cardiovascular diseases than human immunodeficiency virus infected patients not receiving highly active antiretroviral therapy, or the general population. RESEARCH DESIGN AND METHODS: We conducted a computer-based search in representative databases, and also performed manual tracking of citations in selected articles. RESULT: The available evidence suggests an excess risk of cardiovascular events in human immunodeficiency virus-infected persons compared to non-human immunodeficiency virus infected individuals. The use of highly active antiretroviral therapy is associated with increased levels of total cholesterol, triglycerides, low-density lipoprotein and morphological signs of cardiovascular diseases. Some evidence suggested that human immunodeficiency virus-infected individuals on highly active antiretroviral therapy regimens are at increased risk of dyslipidemia, ischemic heart disease, and myocardial infarction, particularly if the highly active antiretroviral therapy regimen contains a protease inhibitor. CONCLUSION: Physicians must weigh the cardiovascular risk against potential benefits when prescribing highly active antiretroviral therapy. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving highly active antiretroviral therapy regimens, particularly for those with known underlying cardiovascular risk

  12. ACADEMIC GENEALOGIES WITH RESPECT TO NARRATIVE IN HUMAN AND SOCIAL SCIENCES AND THEIR IMPLICATION FOR PUBLIC POLICIES

    Science.gov (United States)

    Fujii, Satoshi; Hasegawa, Taiki; Nakano, Takeshi; Hatori, Tsuyoshi

    In human and society science, narrative is regarded as an important issue to understand dynamic actions of human being and society. Therefore, narrative is also expected to be important for public policies that try to improve dynamic actions of human being and society. In th is study, we review academic genealogies with respect to narratives including western philosophy, hermeneutics, historical science, historical philosophy, literary criticism, clinical psychology and sociology, narrative psychology and folklore. Then we discuss how narrative can be pragmatically applied for public policies.

  13. A review of low-level air pollution and adverse effects on human health: implications for epidemiological studies and public policy

    Science.gov (United States)

    Olmo, Neide Regina Simões; do Nascimento Saldiva, Paulo Hilário; Braga, Alfésio Luís Ferreira; Lin, Chin An; de Paula Santos, Ubiratan; Pereira, Luiz Alberto Amador

    2011-01-01

    The aim of this study was to review original scientific articles describing the relationship between atmospheric pollution and damage to human health. We also aimed to determine which of these studies mentioned public policy issues. Original articles relating to atmospheric pollution and human health published between 1995 and 2009 were retrieved from the PubMed database and analyzed. This study included only articles dealing with atmospheric pollutants resulting primarily from vehicle emissions. Three researchers were involved in the final selection of the studies, and the chosen articles were approved by at least two of the three researchers. Of the 84 non-Brazilian studies analyzed, 80 showed an association between atmospheric pollution and adverse effects on human health. Moreover, 66 showed evidence of adverse effects on human health, even at levels below the permitted emission standards. Three studies mentioned public policies aimed at changing emission standards. Similarly, the 29 selected Brazilian studies reported adverse associations with human health, and 27 showed evidence of adverse effects even at levels below the legally permitted emission standards. Of these studies, 16 mentioned public policies aimed at changing emission standards. Based on the Brazilian and non-Brazilian scientific studies that have been conducted, it can be concluded that, even under conditions that are compliant with Brazilian air quality standards, the concentration of atmospheric pollutants in Brazil can negatively affect human health. However, as little discussion of this topic has been generated, this finding demonstrates the need to incorporate epidemiological evidence into decisions regarding legal regulations and to discuss the public policy implications in epidemiological studies. PMID:21655765

  14. Hazard assessment of metals in invasive fish species of the Yamuna River, India in relation to bioaccumulation factor and exposure concentration for human health implications.

    Science.gov (United States)

    Singh, Atul K; Srivastava, Sharad C; Verma, Pankaj; Ansari, Abubakar; Verma, Ambrish

    2014-06-01

    Monitoring of heavy metals was conducted in the Yamuna River considering bioaccumulation factor, exposure concentration, and human health implications which showed contamination levels of copper (Cu), lead (Pb), nickel (Ni), and chromium (Cr) and their dispersion patterns along the river. Largest concentration of Pb in river water was 392 μg L(-1); Cu was 392 μg L(-1) at the extreme downstream, Allahabad and Ni was 146 μg L(-1) at midstream, Agra. Largest concentration of Cu was 617 μg kg(-1), Ni 1,621 μg kg(-1) at midstream while Pb was 1,214 μg kg(-1) at Allahabad in surface sediment. The bioconcentration of Cu, Pb, Ni, and Cr was observed where the largest accumulation of Pb was 2.29 μg kg(-1) in Oreochromis niloticus and 1.55 μg kg(-1) in Cyprinus carpio invaded at Allahabad while largest concentration of Ni was 174 μg kg(-1) in O. niloticus and 124 μg kg(-1) in C. carpio in the midstream of the river. The calculated values of hazard index (HI) for Pb was found more than one which indicated human health concern. Carcinogenic risk value for Ni was again high i.e., 17.02 × 10(-4) which was larger than all other metals studied. The results of this study indicated bioconcentration in fish due to their exposures to heavy metals from different routes which had human health risk implications. Thus, regular environmental monitoring of heavy metal contamination in fish is advocated for assessing food safety since health risk may be associated with the consumption of fish contaminated through exposure to a degraded environment.

  15. Human migration and pig/pork import in the European Union: What are the implications for Taenia solium infections?

    Science.gov (United States)

    Gabriël, S; Johansen, M V; Pozio, E; Smit, G S A; Devleesschauwer, B; Allepuz, A; Papadopoulos, E; van der Giessen, J; Dorny, P

    2015-09-30

    Taenia solium taeniasis/cysticercosis is a neglected zoonotic disease complex occurring primarily in developing countries. Though claimed eradicated from the European Union (EU), an increasing number of human neurocysticercosis cases is being detected. Risk factors such as human migration and movement of pigs/pork, as well as the increasing trend in pig rearing with outside access are discussed in this review. The entry of a tapeworm carrier into the EU seems a lot more plausible than the import of infected pork. The establishment of local transmission in the EU is presently very unlikely. However, considering the potential changes in risk factors, such as the increasing trend in pig farming with outdoor access, the increasing human migration from endemic areas into the EU, this situation might change, warranting the establishment of an early warning system, which should include disease notification of taeniasis/cysticercosis both in human and animal hosts. As currently human-to-human transmission is the highest risk, prevention strategies should focus on the early detection and treatment of tapeworm carriers, and should be designed in a concerted way, across the EU and across the different sectors. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Identification of somatic mutations in postmortem human brains by whole genome sequencing and their implications for psychiatric disorders.

    Science.gov (United States)

    Nishioka, Masaki; Bundo, Miki; Ueda, Junko; Katsuoka, Fumiki; Sato, Yukuto; Kuroki, Yoko; Ishii, Takao; Ukai, Wataru; Murayama, Shigeo; Hashimoto, Eri; Nagasaki, Masao; Yasuda, Jun; Kasai, Kiyoto; Kato, Tadafumi; Iwamoto, Kazuya

    2018-04-01

    Somatic mutations in the human brain are hypothesized to contribute to the functional diversity of brain cells as well as the pathophysiology of neuropsychiatric diseases. However, there are still few reports on somatic mutations in non-neoplastic human brain tissues. This study attempted to unveil the landscape of somatic mutations in the human brain. We explored the landscape of somatic mutations in human brain tissues derived from three individuals with no neuropsychiatric diseases by whole-genome deep sequencing at a depth of around 100. The candidate mutations underwent multi-layered filtering, and were validated by ultra-deep target amplicon sequencing at a depth of around 200 000. Thirty-one somatic mutations were identified in the human brain, demonstrating the utility of whole-genome sequencing of bulk brain tissue. The mutations were enriched in neuron-expressed genes, and two-thirds of the identified somatic single nucleotide variants in the brain tissues were cytosine-to-thymine transitions, half of which were in CpG dinucleotides. Our developed filtering and validation approaches will be useful to identify somatic mutations in the human brain. The vulnerability of neuron-expressed genes to mutational events suggests their potential relevance to neuropsychiatric diseases. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

  17. Respecting the right to access to medicines: Implications of the UN Guiding Principles on Business and Human Rights for the pharmaceutical industry.

    Science.gov (United States)

    Moon, Suerie

    2013-06-14

    What are the human rights responsibilities of pharmaceutical companies with regard to access to medicines? The state-based international human rights framework has long struggled with the issue of the human rights obligations of non-state actors, a question sharpened by economic globalization and the concomitant growing power of private for-profit actors ("business"). In 2011, after a six-year development process, the UN Human Rights Council unanimously endorsed the Guiding Principles advanced by the UN Secretary General's Special Representative on Business and Human Rights, John Ruggie. The Ruggie Principles sought to clarify and differentiate the responsibilities of states and non-state actors-in this case, "business" -with respect to human rights. The framework centered on "three core principles: the state duty to protect against human rights abuses by third parties, including business; the corporate responsibility to respect human rights; and the need for more effective access to remedies." The "Protect, Respect, and Remedy" Framework emerged from a review of many industrial sectors operating from local to global scales, in many regions of the world, and involving multiple stakeholder consultations. However, their implications for the pharmaceutical industry regarding access to medicines remain unclear. This article analyzes the 2008 Human Rights Guidelines for Pharmaceutical Companies in relation to Access to Medicines advanced by then-UN Special Rapporteur on the Right to Health, Paul Hunt, in light of the Ruggie Principles. It concludes that some guidelines relate directly to the industry's responsibility to respect the right to access to medicines, and form a normative baseline to which firms should be held accountable. It also finds that responsibility for other guidelines may better be ascribed to states than to private actors, based on conceptual and practical considerations. While not discouraging the pharmaceutical industry from making additional

  18. STUDY ON ORGANIZATIONAL PATHOLOGY AND IMPLICATIONS ON HUMAN RESOURCES JOB SATISFACTION, ALSO ON THE EMPLOYMENT OF THE LABOR MARKET

    Directory of Open Access Journals (Sweden)

    Diana-Elena, SERB

    2014-11-01

    Full Text Available People need to face the demands resulting induced neurotic styles of their leaders. The result is lower morale, affect behavior, dissatisfaction at work. This paper aims to present the point of view of theoretical and practical implications of failures in the organization on job satisfaction of employees. The practical part of this article is the analysis of statistically labor employment level , and a marketing research field, a survey using questionnaire as the main instrument. The main objectives during the research aims: knowledge labor employment in Romania, identify employee satisfaction on labor relations between managers and subordinates, knowledge of the involvement of the manager in providing a suitable work environment, to determine the extent the problems arising in the workplace creates dissatisfaction which ultimately rebounds on return. The main results drawn as a result of research carried out show that existing pathology in an organization is felt on one side by the employee the aggression and persecution has implications for morale, and on the other hand these disturbances are felt at employment in that workplace, stress employees resign and this leads to higher unemployment.

  19. Human-crocodile conflict and conservation implications of Saltwater Crocodiles Crocodylus porosus (Reptilia: Crocodylia: Crocodylidae in Sri Lanka

    Directory of Open Access Journals (Sweden)

    A.A. Thasun Amarasinghe

    2015-04-01

    Full Text Available Human-wildlife conflict occurs when human requirements encroach on those of wildlife populations, with potential costs to both humans and wild animals.  As top predators in most inland waters, crocodilians are involved in human-wildlife conflicts in many countries.  Here we present findings of a 5-year survey on human-crocodile conflict on the island of Sri Lanka and relate the results to improving management practices. We aimed to quantify and understand the causes of human-crocodile conflict in Sri Lanka, and propose solutions to mitigate it.  Visual encounter surveys were carried out to estimate the population size of Saltwater Crocodiles. We recorded 778 sightings of Saltwater Crocodiles at 262 of 400 locations surveyed, and estimate the total population to comprise more than 2000 non-hatchlings and to have increased at an average rate of 5% p.a. since 1978. We propose four crocodile vigilance zones within the wet zone and one crocodile vigilance zone within the dry zone of the country. Specific threats to Saltwater Crocodiles identified in crocodile vigilance zones were: habitat destruction and loss; illegal killing and harvesting (17 killings out of fear, ~200 incidents of killing for meat and skins, ~800 eggs annually for consumption; unplanned translocations; and, interaction with urbanization (10 incidents of crocodiles being run over by trains/vehicles and electrocution. Additionally, 33 cases of crocodile attacks on humans were recorded [8 fatal, 25 non-fatal (minor to grievous injuries] and more than 50 incidents of attacks on farm and pet animals. 

  20. Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G--possible implications for human reproduction and autoimmune disease

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F; Christiansen, Ole B

    2005-01-01

    ). We found a significant linkage disequilibrium between HLA-DR3 and HLA-G*010102 in both the RSA and control populations. For all four studied HLA loci, the alleles in the haplotype HLA-DRB1*03.DQA1*05.DQB1*02.G*010102 was in clear linkage disequilibrium. This HLA haplotype has repeatedly been...... associated with different autoimmune diseases but also with RSA. The G*010102 allele includes a 14-bp sequence polymorphism in the 3' untranslated region of the gene, which has been associated with differences in HLA-G mRNA alternative splicing and stability. This 14-bp polymorphism has also been associated...... with RSA, pre-eclampsia, and outcome of in vitro fertilization. Implications of HLA polymorphism--and other polymorphic genes in the MHC for pregnancy outcome--and for autoimmune diseases during pregnancy are discussed....

  1. Review of the physiology of human thermal comfort while exercising in urban landscapes and implications for bioclimatic design

    Science.gov (United States)

    Vanos, Jennifer K.; Warland, Jon S.; Gillespie, Terry J.; Kenny, Natasha A.

    2010-07-01

    This review comprehensively examines scientific literature pertaining to human physiology during exercise, including mechanisms of heat formation and dissipation, heat stress on the body, the importance of skin temperature monitoring, the effects of clothing, and microclimatic measurements. This provides a critical foundation for microclimatologists and biometeorologists in the understanding of experiments involving human physiology. The importance of the psychological aspects of how an individual perceives an outdoor environment are also reviewed, emphasizing many factors that can indirectly affect thermal comfort (TC). Past and current efforts to develop accurate human comfort models are described, as well as how these models can be used to develop resilient and comfortable outdoor spaces for physical activity. Lack of suitable spaces plays a large role in the deterioration of human health due to physical inactivity, leading to higher rates of illness, heart disease, obesity and heat-related casualties. This trend will continue if urban designers do not make use of current knowledge of bioclimatic urban design, which must be synthesized with physiology, psychology and microclimatology. Increased research is required for furthering our knowledge on the outdoor human energy balance concept and bioclimatic design for health and well-being in urban areas.

  2. Comparative primate obstetrics: Observations of 15 diurnal births in wild gelada monkeys (Theropithecus gelada) and their implications for understanding human and nonhuman primate birth evolution.

    Science.gov (United States)

    Nguyen, Nga; Lee, Laura M; Fashing, Peter J; Nurmi, Niina O; Stewart, Kathrine M; Turner, Taylor J; Barry, Tyler S; Callingham, Kadie R; Goodale, C Barret; Kellogg, Bryce S; Burke, Ryan J; Bechtold, Emily K; Claase, Megan J; Eriksen, G Anita; Jones, Sorrel C Z; Kerby, Jeffrey T; Kraus, Jacob B; Miller, Carrie M; Trew, Thomas H; Zhao, Yi; Beierschmitt, Evan C; Ramsay, Malcolm S; Reynolds, Jason D; Venkataraman, Vivek V

    2017-05-01

    The birth process has been studied extensively in many human societies, yet little is known about this essential life history event in other primates. Here, we provide the most detailed account of behaviors surrounding birth for any wild nonhuman primate to date. Over a recent ∼10-year period, we directly observed 15 diurnal births (13 live births and 2 stillbirths) among geladas (Theropithecus gelada) at Guassa, Ethiopia. During each birth, we recorded the occurrence (or absence) of 16 periparturitional events, chosen for their potential to provide comparative evolutionary insights into the factors that shaped birth behaviors in humans and other primates. We found that several events (e.g., adopting standing crouched positions, delivering infants headfirst) occurred during all births, while other events (e.g., aiding the infant from the birth canal, licking infants following delivery, placentophagy) occurred during, or immediately after, most births. Moreover, multiparas (n = 9) were more likely than primiparas (n = 6) to (a) give birth later in the day, (b) isolate themselves from nearby conspecifics while giving birth, (c) aid the infant from the birth canal, and (d) consume the placenta. Our results suggest that prior maternal experience may contribute to greater competence or efficiency during the birth process. Moreover, face presentations (in which infants are born with their neck extended and their face appearing first, facing the mother) appear to be the norm for geladas. Lastly, malpresentations (in which infants are born in the occiput anterior position more typical of human infants) may be associated with increased mortality in this species. We compare the birth process in geladas to those in other primates (including humans) and discuss several key implications of our study for advancing understanding of obstetrics and the mechanism of labor in humans and nonhuman primates. © 2017 Wiley Periodicals, Inc.

  3. Middle palaeolithic and neolithic occupations around Mundafan Palaeolake, Saudi Arabia: implications for climate change and human dispersals.

    Directory of Open Access Journals (Sweden)

    Rémy Crassard

    Full Text Available The Arabian Peninsula is a key region for understanding climate change and human occupation history in a marginal environment. The Mundafan palaeolake is situated in southern Saudi Arabia, in the Rub' al-Khali (the 'Empty Quarter', the world's largest sand desert. Here we report the first discoveries of Middle Palaeolithic and Neolithic archaeological sites in association with the palaeolake. We associate the human occupations with new geochronological data, and suggest the archaeological sites date to the wet periods of Marine Isotope Stage 5 and the Early Holocene. The archaeological sites indicate that humans repeatedly penetrated the ameliorated environments of the Rub' al-Khali. The sites probably represent short-term occupations, with the Neolithic sites focused on hunting, as indicated by points and weaponry. Middle Palaeolithic assemblages at Mundafan support a lacustrine adaptive focus in Arabia. Provenancing of obsidian artifacts indicates that Neolithic groups at Mundafan had a wide wandering range, with transport of artifacts from distant sources.

  4. Functional variability of snake venom metalloproteinases: adaptive advantages in targeting different prey and implications for human envenomation.

    Directory of Open Access Journals (Sweden)

    Juliana L Bernardoni

    Full Text Available Snake venom metalloproteinases (SVMPs are major components in most viperid venoms that induce disturbances in the hemostatic system and tissues of animals envenomated by snakes. These disturbances are involved in human pathology of snake bites and appear to be essential for the capture and digestion of snake's prey and avoidance of predators. SVMPs are a versatile family of venom toxins acting on different hemostatic targets which are present in venoms in distinct structural forms. However, the reason why a large number of different SVMPs are expressed in some venoms is still unclear. In this study, we evaluated the interference of five isolated SVMPs in blood coagulation of humans, birds and small rodents. P-III class SVMPs (fractions Ic, IIb and IIc possess gelatinolytic and hemorrhagic activities, and, of these, two also show fibrinolytic activity. P-I class SVMPs (fractions IVa and IVb are only fibrinolytic. P-III class SVMPs reduced clotting time of human plasma. Fraction IIc was characterized as prothrombin activator and fraction Ic as factor X activator. In the absence of Ca2+, a firm clot was observed in chicken blood samples with fractions Ic, IIb and partially with fraction IIc. In contrast, without Ca2+, only fraction IIc was able to induce a firm clot in rat blood. In conclusion, functionally distinct forms of SVMPs were found in B. neuwiedi venom that affect distinct mechanisms in the coagulation system of humans, birds and small rodents. Distinct SVMPs appear to be more specialized to rat or chicken blood, strengthening the current hypothesis that toxin diversity enhances the possibilities of the snakes for hunting different prey or evading different predators. This functional diversity also impacts the complexity of human envenoming since different hemostatic mechanisms will be targeted by SVMPs accounting for the complexity of the response of humans to venoms.

  5. Advance Directives of Will (Living Will: Ethical and Legal Implications Based on the Principle of Dignity of Human Person

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Alkimim

    2016-12-01

    Full Text Available This paper, with methodology of philosophical, bibliographical and documentary research intends to apply the principle of dignity of human person to the vicissitudes around the advance directives of will, to the ethical aspects disciplined by the Code of Medical Ethics, as well as to what regards the legal aspects, involving the Federal Constitution, the Civil Code, the Code of Medical Ethics and the Resolution 1995/2012 (CFM. The principle of dignity of human person along with the consequent application in the principles of bioethics is considered in a personalistic perspective. This kind of approach is indicative of the interdisciplinarity of bioethics.

  6. Social implications of the Human Genome Project: Policy roundtable series and journals. Final progress report, March 15, 2001 - March 15, 2002

    Energy Technology Data Exchange (ETDEWEB)

    Seiguer, Erica

    2002-12-30

    This report reflects the activities of the Harvard Health Caucus at Harvard Medical School that were supported, in part, by the Department of Energy. The following policy roundtables and panels were held: Spring 2001 Policy Roundtable Series: The social implications of the Human Genome Project; Spring 2002 Policy Roundtable Series: Managing globalization to improve health; 13 February 2002 Keynote Address: The globalization of health; 25 February 2002 Healthier or Wealthier: Which comes first in the new global era?; 28 February 2002 The crisis of neglected diseases: Creating R&D incentives for diseases of developing countries; 7 March 2002 Health care education in the developing world: Bridging global and local health care practices; 20 March 2002 Building a legal framework for global health: How can the US and UN work to reduce global disparities?; 25 April 2002 The role of mass media and tobacco control efforts. Caucus organizational information is also included.

  7. Effect of human disturbance on the prey of tiger in the Chitwan National Park - Implications for park management

    Czech Academy of Sciences Publication Activity Database

    Bhattarai, Bishnu Prasad; Kindlmann, Pavel

    2013-01-01

    Roč. 131, DEC 15 2013 (2013), s. 343-350 ISSN 0301-4797 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MŠk LC06073 Institutional support: RVO:67179843 Keywords : human disturbance * ungulates * conservation * habitats * predators Subject RIV: EH - Ecology, Behaviour Impact factor: 3.188, year: 2013

  8. Effect of stimulus parameters and contraction level on inhibitory responses in human jaw-closing muscles: Implications for contingent stimulation

    DEFF Research Database (Denmark)

    Jadidi, F; Wang, K; Arendt-Nielsen, Lars

    2009-01-01

      Objective: Examine the effect of stimulus duration as well as stimulus intensity and level of muscle contraction on the inhibitory responses in human jaw-closing muscles. Design: The inhibitory jaw-reflexes, ES1 and ES2, were recorded in the surface electromyogram (EMG) of masseter and temporal...

  9. Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health.

    Science.gov (United States)

    Bryan, Jeffrey N

    2015-05-01

    Fetal microchimerism is the co-existence of small numbers of cells from genetically distinct individuals living within a mother's body following pregnancy. During pregnancy, bi-directional exchange of cells occurs resulting in maternal microchimerism and even sibling microchimerism in offspring. The presence of fetal microchimerism has been identified with lower frequency in patients with cancers such as breast and lymphoma and with higher frequency in patients with colon cancer and autoimmune diseases. Microchimeric cells have been identified in healing and healed tissues as well as normal and tumor tissues. This has led to the hypothesis that fetal microchimerism may play a protective role in some cancers and may provoke other cancers or autoimmune disease. The long periods of risk for these diseases make it a challenge to prospectively study this phenomenon in human populations. Dogs get similar cancers as humans, share our homes and environmental exposures, and live compressed life-spans, allowing easier prospective study of disease development. This review describes the current state of understanding of fetal microchimerism in humans and dogs and highlights the similarities of the common cancers mammary carcinoma, lymphoma, and colon cancer between the two species. Study of fetal microchimerism in dogs might hold the key to characterization of the type and function of microchimeric cells and their role in health and disease. Such an understanding could then be applied to preventing and treating disease in humans.

  10. Some Sociological Alternatives to Human Capital Theory and Their Implications for Research on Post-Compulsory Education and Training.

    Science.gov (United States)

    Fevre, Ralph; Rees, Gareth; Gorard, Stephen

    1999-01-01

    Based on research in South Wales, a sociological theory of participation in education and training is developed, identifying types of orientations: functional avoidance, instrumental credentialism, and vocational transformation. The inclusion of sociological insights in human-capital development policy is recommended. (SK)

  11. Short wavelength light filtering by the natural human lens and IOLs -- implications for entrainment of circadian rhythm

    DEFF Research Database (Denmark)

    Brøndsted, Adam Elias; Lundeman, Jesper Holm; Kessel, Line

    2013-01-01

    Photoentrainment of circadian rhythm begins with the stimulation of melanopsin containing retinal ganglion cells that respond directly to blue light. With age, the human lens becomes a strong colour filter attenuating transmission of short wavelengths. The purpose of the study was to examine the ...

  12. Regulation of cytochrome P4501A1 expression by hyperoxia in human lung cell lines: Implications for hyperoxic lung injury

    International Nuclear Information System (INIS)

    Bhakta, Kushal Y.; Jiang, Weiwu; Couroucli, Xanthi I.; Fazili, Inayat S.; Muthiah, Kathirvel; Moorthy, Bhagavatula

    2008-01-01

    Supplemental oxygen, used to treat pulmonary insufficiency in newborns, contributes to the development of bronchopulmonary dysplasia (BPD). Cytochrome P4501A enzymes are induced by hyperoxia in animal models, but their role in human systems is unknown. Here we investigated the molecular mechanisms of induction of CYP1A1 by hyperoxia in human lung cell lines. Three human lung cell lines were exposed to hyperoxia (95% O2) for 0-72 h, and CYP1A1 activities, apoprotein contents, and mRNA levels were determined. Hyperoxia significantly induced CYP1A1 activity and protein contents (2-4 fold), and mRNA levels (30-40 fold) over control in each cell line. Transfection of a CYP1A1 promoter/luciferase reporter construct, followed by hyperoxia (4-72 h), showed marked (2-6 fold) induction of luciferase expression. EMSA and siRNA experiments strongly suggest that the Ah receptor (AHR) is involved in the hyperoxic induction of CYP1A1. MTT reduction assays showed attenuation of cell injury with the CYP1A1 inducer beta-naphthoflavone (BNF). Our results strongly suggest that hyperoxia transcriptionally activates CYP1A1 expression in human lung cell lines by AHR-dependent mechanisms, and that CYP1A1 induction is associated with decreased toxicity. This novel finding of induction of CYP1A1 in the absence of exogenous AHR ligands could lead to novel interventions in the treatment of BPD

  13. Draft Genome Sequences of Four Salmonella enterica subsp. enterica Serovar Enteritidis Strains Implicated in Infections of Avian and Human Hosts

    KAUST Repository

    An, Ran; Lin, Pengpeng; Bougouffa, Salim; Essack, Magbubah; Boxrud, David; Bajic, Vladimir B.; Vidovic, Sinisa

    2018-01-01

    Salmonella enterica subsp. enterica serovar Enteritidis is a wide-host-range pathogen. Occasionally, it is involved in invasive infections, leading to a high mortality rate. Here, we present the draft genome sequences of four S Enteritidis strains obtained from human and avian hosts that had been involved in bacteremia, gastroenteritis, and primary infections.

  14. Trends Affecting Ohio State University Extension in the 21st Century and the Implications for Human Capital

    Science.gov (United States)

    Cochran, Graham R.; Ferrari, Theresa M.; Chen, Claire Yueh-Ti

    2012-01-01

    Research with a diverse array of organizations in the public and private sectors has documented a common set of trends affecting organizations and their human capital in the 21st century. Similar trends have been identified as important for Extension organizations and the Cooperative Extension System. It is important to determine if such trends…

  15. Nitrogen Solubility in Adipose Tissues of Diving Animals: Implications for Human Divers and for Modeling Diving Physiology

    Science.gov (United States)

    2016-11-01

    UNC-CH ethics /privacy website so I could be approved, only to discover from a different UNC-CH administrative office that this was not needed. We...water and extracted human fat. Technical Report, USAF School of Aerospace Medicine. SAM-TR 94: 1-9. Koopman, H.N. 2007. Phylogenetic, ecological , and

  16. The Relationships between Human Capital, Implicit Views of Intelligence, and Literacy Performance: Implications for the Obama Education Era

    Science.gov (United States)

    Williams, Rihana S.; Ari, Omer; Dortch, Cedrick

    2011-01-01

    African American adolescents from families with low levels of human capital (i.e., caregiver level of education) are at risk for poor early adult outcomes. The current study examined the relationships among 48 African American high school students' literacy performance (e.g., reading and vocabulary), their implicit views of intelligence, their…

  17. Draft Genome Sequences of Four Salmonella enterica subsp. enterica Serovar Enteritidis Strains Implicated in Infections of Avian and Human Hosts

    KAUST Repository

    An, Ran

    2018-01-24

    Salmonella enterica subsp. enterica serovar Enteritidis is a wide-host-range pathogen. Occasionally, it is involved in invasive infections, leading to a high mortality rate. Here, we present the draft genome sequences of four S Enteritidis strains obtained from human and avian hosts that had been involved in bacteremia, gastroenteritis, and primary infections.

  18. National Implications for Urban School Systems: Strategic Planning in the Human Resource Management Department in a Large Urban School District

    Science.gov (United States)

    Johnson, Clarence; Kritsonis, William Allan

    2007-01-01

    This article addresses several key ongoing issues in a large urban school district. Literature focuses on what make a large urban school district effective in Human Resource Management. The effectiveness is addressed through recruitment and retention practices. A comparison of the school district with current research is the main approach to the…

  19. Introducing Human Rights Education in the Confucian Society of Taiwan: Its Implications for Ethical Leadership in Education.

    Science.gov (United States)

    Hwang, Kwang-Kuo

    2001-01-01

    Discusses recent introduction of human-rights education in Taiwan. Describes essential characteristics of Confucian ethics; compares Confucianism with ethical leadership in education. Discusses relationship between findings on the use of corporal punishment in Taiwanese schools and ethical leadership. Describes worldwide use of corporal punishment…

  20. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  1. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

    2015-01-01

    BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  2. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

  3. The Human Tripeptide GHK-Cu in Prevention of Oxidative Stress and Degenerative Conditions of Aging: Implications for Cognitive Health

    Directory of Open Access Journals (Sweden)

    Loren Pickart

    2012-01-01

    Full Text Available Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging—detrimental epigenetic modifications—has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline.

  4. Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

    Science.gov (United States)

    Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

    2013-08-01

    Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

  5. Shared human-chimpanzee pattern of perinatal femoral shaft morphology and its implications for the evolution of hominin locomotor adaptations.

    Directory of Open Access Journals (Sweden)

    Naoki Morimoto

    Full Text Available Acquisition of bipedality is a hallmark of human evolution. How bipedality evolved from great ape-like locomotor behaviors, however, is still highly debated. This is mainly because it is difficult to infer locomotor function, and even more so locomotor kinematics, from fossil hominin long bones. Structure-function relationships are complex, as long bone morphology reflects phyletic history, developmental programs, and loading history during an individual's lifetime. Here we discriminate between these factors by investigating the morphology of long bones in fetal and neonate great apes and humans, before the onset of locomotion.Comparative morphometric analysis of the femoral diaphysis indicates that its morphology reflects phyletic relationships between hominoid taxa to a greater extent than taxon-specific locomotor adaptations. Diaphyseal morphology in humans and chimpanzees exhibits several shared-derived features, despite substantial differences in locomotor adaptations. Orangutan and gorilla morphologies are largely similar, and likely represent the primitive hominoid state.These findings are compatible with two possible evolutionary scenarios. Diaphyseal morphology may reflect retained adaptive traits of ancestral taxa, hence human-chimpanzee shared-derived features may be indicative of the locomotor behavior of our last common ancestor. Alternatively, diaphyseal morphology might reflect evolution by genetic drift (neutral evolution rather than selection, and might thus be more informative about phyletic relationships between taxa than about locomotor adaptations. Both scenarios are consistent with the hypothesis that knuckle-walking in chimpanzees and gorillas resulted from convergent evolution, and that the evolution of human bipedality is unrelated to extant great ape locomotor specializations.

  6. A homologous form of human interleukin 16 is implicated in microglia recruitment following nervous system injury in leech Hirudo medicinalis.

    Science.gov (United States)

    Croq, Françoise; Vizioli, Jacopo; Tuzova, Marina; Tahtouh, Muriel; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Cruikshank, William W; Pestel, Joel; Lefebvre, Christophe

    2010-11-01

    In contrast to mammals, the medicinal leech Hirudo medicinalis can completely repair its central nervous system (CNS) after injury. This invertebrate model offers unique opportunities to study the molecular and cellular basis of the CNS repair processes. When the leech CNS is injured, microglial cells migrate and accumulate at the site of lesion, a phenomenon known to be essential for the usual sprouting of injured axons. In the present study, we demonstrate that a new molecule, designated HmIL-16, having functional homologies with human interleukin-16 (IL-16), has chemotactic activity on leech microglial cells as observed using a gradient of human IL-16. Preincubation of microglial cells either with an anti-human IL-16 antibody or with anti-HmIL-16 antibody significantly reduced microglia migration induced by leech-conditioned medium. Functional homology was demonstrated further by the ability of HmIL-16 to promote human CD4+ T cell migration which was inhibited by antibody against human IL-16, an IL-16 antagonist peptide or soluble CD4. Immunohistochemistry of leech CNS indicates that HmIL-16 protein present in the neurons is rapidly transported and stored along the axonal processes to promote the recruitment of microglial cells to the injured axons. To our knowledge, this is the first identification of a functional interleukin-16 homologue in invertebrate CNS. The ability of HmIL-16 to recruit microglial cells to sites of CNS injury suggests a role for HmIL-16 in the crosstalk between neurons and microglia in the leech CNS repair.

  7. Persistent oscillations and backward bifurcation in a malaria model with varying human and mosquito populations: implications for control.

    Science.gov (United States)

    Ngonghala, Calistus N; Teboh-Ewungkem, Miranda I; Ngwa, Gideon A

    2015-06-01

    We derive and study a deterministic compartmental model for malaria transmission with varying human and mosquito populations. Our model considers disease-related deaths, asymptomatic immune humans who are also infectious, as well as mosquito demography, reproduction and feeding habits. Analysis of the model reveals the existence of a backward bifurcation and persistent limit cycles whose period and size is determined by two threshold parameters: the vectorial basic reproduction number Rm, and the disease basic reproduction number R0, whose size can be reduced by reducing Rm. We conclude that malaria dynamics are indeed oscillatory when the methodology of explicitly incorporating the mosquito's demography, feeding and reproductive patterns is considered in modeling the mosquito population dynamics. A sensitivity analysis reveals important control parameters that can affect the magnitudes of Rm and R0, threshold quantities to be taken into consideration when designing control strategies. Both Rm and the intrinsic period of oscillation are shown to be highly sensitive to the mosquito's birth constant λm and the mosquito's feeding success probability pw. Control of λm can be achieved by spraying, eliminating breeding sites or moving them away from human habitats, while pw can be controlled via the use of mosquito repellant and insecticide-treated bed-nets. The disease threshold parameter R0 is shown to be highly sensitive to pw, and the intrinsic period of oscillation is also sensitive to the rate at which reproducing mosquitoes return to breeding sites. A global sensitivity and uncertainty analysis reveals that the ability of the mosquito to reproduce and uncertainties in the estimations of the rates at which exposed humans become infectious and infectious humans recover from malaria are critical in generating uncertainties in the disease classes.

  8. Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Klein Michael L

    2011-07-01

    Full Text Available Abstract Background Age related macular degeneration (AMD is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH, the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD. Methods Human peripheral blood mononuclear cells (PBMCs were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500. Results We show that C5a promotes interleukin (IL-22 and IL-17 expression by human CD4+ T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4+ cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls. Conclusions Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.

  9. Epigenetic modulation of cancer-germline antigen gene expression in tumorigenic human mesenchymal stem cells: implications for cancer therapy

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Burns, Jorge S; Nielsen, Ole

    2009-01-01

    Cancer-germline antigens are promising targets for cancer immunotherapy, but whether such therapies will also eliminate the primary tumor stem cell population remains undetermined. We previously showed that long-term cultures of telomerized adult human bone marrow mesenchymal stem cells can...... spontaneously evolve into tumor-initiating, mesenchymal stem cells (hMSC-TERT20), which have characteristics of clinical sarcoma cells. In this study, we used the hMSC-TERT20 tumor stem cell model to investigate the potential of cancer-germline antigens to serve as tumor stem cell targets. We found...... of cancer-germline antigens in hMSC-TERT20 cells, while their expression levels in primary human mesenchymal stem cells remained unaffected. The expression pattern of cancer-germline antigens in tumorigenic mesenchymal stem cells and sarcomas, plus their susceptibility to enhancement by epigenetic...

  10. Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

    Science.gov (United States)

    Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

    2002-01-01

    Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

  11. A Closer Look at Bacteroides: Phylogenetic Relationship and Genomic Implications of a Life in the Human Gut

    DEFF Research Database (Denmark)

    Karlsson, Fredrik H.; Ussery, David; Nielsen, Jens

    2011-01-01

    The human gut is extremely densely inhabited by bacteria mainly from two phyla, Bacteroidetes and Firmicutes, and there is a great interest in analyzing whole-genome sequences for these species because of their relation to human health and disease. Here, we do whole-genome comparison of 105...... of extracytoplasmic function σ factors (ECF σ factors) and two component systems for extracellular signal transduction compared to other Bacteroidetes/Chlorobi species. A whole-genome phylogenetic analysis shows a very little difference between the Parabacteroides and Bacteroides genera. Further analysis shows...... of members of the Bacteroidetes/Chlorobi phylum by whole genome comparison. Gut living Bacteroides have an enriched set of glycan, vitamin, and cofactor enzymes important for diet digestion....

  12. In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

    International Nuclear Information System (INIS)

    Timraz, Sara B.H.; Farhat, Ilyas A.H.; Alhussein, Ghada; Christoforou, Nicolas; Teo, Jeremy C.M.

    2016-01-01

    In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, and reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.

  13. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening

    OpenAIRE

    Katki, Hormuzd A.; Cheung, Li C.; Fetterman, Barbara; Castle, Philip E.; Sundaram, Rajeshwari

    2015-01-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interv...

  14. Physician Decisions to Defer Antiretroviral Therapy in Key Populations: Implications for Reducing Human Immunodeficiency Virus Incidence and Mortality in Malaysia

    OpenAIRE

    Ferro, Enrico G.; Culbert, Gabriel J.; Wickersham, Jeffrey A.; Marcus, Ruthanne; Steffen, Alana D.; Pauls, Heather A.; Westergaard, Ryan P.; Lee, Christopher K.; Kamarulzaman, Adeeba; Altice, Frederick L.

    2017-01-01

    Abstract Background. Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. Methods. Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and...

  15. In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Timraz, Sara B.H., E-mail: sara.timraz@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Farhat, Ilyas A.H., E-mail: ilyas.farhat@outlook.com [Department of Applied Mathematics and Sciences, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Alhussein, Ghada, E-mail: ghada.alhussein@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Christoforou, Nicolas, E-mail: nicolas.christoforou@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Department of Biomedical Engineering, Duke University, Durham, NC 27708 (United States); Teo, Jeremy C.M., E-mail: jeremy.teo@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates)

    2016-05-01

    In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, and reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.

  16. Clearance Prediction Methodology Needs Fundamental Improvement: Trends Common to Rat and Human Hepatocytes/Microsomes and Implications for Experimental Methodology.

    Science.gov (United States)

    Wood, F L; Houston, J B; Hallifax, D

    2017-11-01

    Although prediction of clearance using hepatocytes and liver microsomes has long played a decisive role in drug discovery, it is widely acknowledged that reliably accurate prediction is not yet achievable despite the predominance of hepatically cleared drugs. Physiologically mechanistic methodology tends to underpredict clearance by several fold, and empirical correction of this bias is confounded by imprecision across drugs. Understanding the causes of prediction uncertainty has been slow, possibly reflecting poor resolution of variables associated with donor source and experimental methods, particularly for the human situation. It has been reported that among published human hepatocyte predictions there was a tendency for underprediction to increase with increasing in vivo intrinsic clearance, suggesting an inherent limitation using this particular system. This implied an artifactual rate limitation in vitro, although preparative effects on cell stability and performance were not yet resolved from assay design limitations. Here, to resolve these issues further, we present an up-to-date and comprehensive examination of predictions from published rat as well as human studies (where n = 128 and 101 hepatocytes and n = 71 and 83 microsomes, respectively) to assess system performance more independently. We report a clear trend of increasing underprediction with increasing in vivo intrinsic clearance, which is similar both between species and between in vitro systems. Hence, prior concerns arising specifically from human in vitro systems may be unfounded and the focus of investigation in the future should be to minimize the potential in vitro assay limitations common to whole cells and subcellular fractions. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  17. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota.

    Science.gov (United States)

    Milani, Christian; Duranti, Sabrina; Bottacini, Francesca; Casey, Eoghan; Turroni, Francesca; Mahony, Jennifer; Belzer, Clara; Delgado Palacio, Susana; Arboleya Montes, Silvia; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Rodriguez, Juan Miguel; Bode, Lars; de Vos, Willem; Gueimonde, Miguel; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2017-12-01

    The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and

  18. Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

    Science.gov (United States)

    2013-07-01

    transfected with RNA. NatBiotech. 1998;16:364-369. 20. Heiser A, Dahm P, Yancey DR, et al. Human dendritic cells transfected with RNA encoding prostate...specific antigen stimulate prostate-specific CTL responses in vitro. J Immunol. 2000;164(10):5508-5514. 21. Heiser A, Maurice MA, Yancey DR...primary and metastatic tumors. Cancer Res. 2001;61(8):3388-3393. 22. Heiser A, Coleman D, Dannull J, et al. Autologous dendritic cells transfected

  19. Widespread molecular patterns associated with drug sensitivity in breast cancer cell lines, with implications for human tumors.

    Directory of Open Access Journals (Sweden)

    Chad J Creighton

    Full Text Available BACKGROUND: Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1 set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. METHODS AND RESULTS: With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA, and incorporated all profiled features (not only the "best" predictive ones. As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser were used to "predict" the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas. Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers. CONCLUSIONS: Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of

  20. Insisting on the Healer's Art: The Implications of Required Participation in a Medical School Course on Values and Humanism.

    Science.gov (United States)

    Rabow, Michael W; Lapedis, Marissa; Feingold, Anat; Thomas, Mark; Remen, Rachel N

    2016-01-01

    Elective courses, by definition, allow medical students to self-select for participation in the class. In a small-group learning setting, students uninterested or not ready for a particular learning topic might change the educational experience ("poison the well") for those students most interested in the topic. It is not known how medical students required to take a course in humanism (that they otherwise would not have elected to take) might be impacted by the course or how their presence might affect students originally interested in the course. Medical students in a required course on humanism and values in medicine will have different experiences based on whether a particular student might have or not have elected to enroll in the course. Students uninterested in taking a course in humanism and values, but required to enroll, will limit the benefit of the course for those students originally interested in participating. In 2012, all 1st-year students at a U.S. medical school were required to take the Healer's Art, an elective on professional values and humanism offered at more than 90 other schools in the United States and internationally. Students completed pre/postcourse surveys assessing emotional exhaustion, work engagement, positive emotions, and cynicism. We analyzed differences between those who would have elected to take the course (Elective students) and those who would not have elected to take it (Required students). Elective students did not differ from Required students in baseline demographic characteristics, emotional exhaustion, work engagement, or positive emotions. At baseline, Elective students did report feeling safer to talk openly, a greater sense of community, and higher levels of cynicism. Over time, there were no differences in course evaluations or outcomes between Elective and Required students. Required students do not differ greatly from those who would have elected to take Healer's Art, and all students appear to have similar

  1. ‘Bound Coolies’ and Other Indentured Workers in the Caribbean: Implications for debates about human trafficking and modern slavery

    Directory of Open Access Journals (Sweden)

    Kamala Kempadoo

    2017-09-01

    Full Text Available Under systems of indenture in the Caribbean, Europeans such as Irish, Scots and Portuguese, as well as Asians, primarily Indians, Chinese and Indonesians, were recruited, often under false pretences, and transported to the ‘New World’, where they were bound to an employer and the plantation in a state of ‘interlocking incarceration’. Indentureship not only preceded, co-existed with, and survived slavery in the Caribbean, but was distinct in law and in practice from slavery. This article argues that the conditions of Caribbean indenture can be seen to be much more analogous to those represented in contemporary discussions about human trafficking and ‘modern slavery’ than those of slavery. Caribbean histories of indenture, it is proposed, can provide more appropriate conceptual tools for thinking about unfree labour today—whether state or privately sponsored—than the concept of slavery, given the parallels between this past migrant labour system in the Caribbean and those we witness and identify today as ‘modern slavery’ or human trafficking. This article thus urges a move away from the conflation of slavery and human trafficking with all forced, bonded and migrant labour, as is commonly the case, and for greater attention for historical evidence.

  2. The Fibularis (Peroneus Tertius Muscle in Humans: A Meta-Analysis of Anatomical Studies with Clinical and Evolutionary Implications

    Directory of Open Access Journals (Sweden)

    Kaissar Yammine

    2017-01-01

    Full Text Available Being considered an exclusive human structure for a long time, fibularis tertius (FT is believed to have a secondary function of foot dorsiflexion and eversion. This study is an attempt to approach the issue from an anatomical perspective. A systematic literature search identified 35 studies (7601 legs which met the inclusion criteria. The weighted results of FT presence were as follows: an “adult cadaveric” frequency of 93.2% and a clinical frequency of 80%. The most common FT origin and insertion sites were the distal half of fibula and the base of the 5th metatarsal, respectively. In 95% of cases, an accessory fibular muscle was detected when FT was lacking. We demonstrated that the discrepancy found between the adult cadaveric and clinical frequency values would point out a probable bias in interpreting previous kinesiological results. On an evolutionary level, comparative anatomy demonstrated a very low FT prevalence among monkeys while reaching a frequency of 30% in gorillas, the only non-human apes having an almost exclusive terrestrial locomotion. The consistent prevalence among humans and the presence of similar functional muscles when it is missing would support an essential role of FT during the phylogenetic development of the erect bipedal posture and probably during gait.

  3. Implications of the quadratic cell survival curve and human skin radiation ''tolerance doses'' on fractionation and superfractionation dose selection

    International Nuclear Information System (INIS)

    Douglas, B.G.

    1982-01-01

    An analysis of early published multifraction orthovoltage human acute skin irradiation tolerance isoeffect doses is presented. It indicates that human acute skin radiation reactions may result from the repetition, with each dose fraction, of a cell survival curve of the form: S = e/sup -(αD + βD 2 )/). The analysis also shows no need for an independent proliferation related time factor for skin, for daily treatments of six weeks or less in duration. The value obtained for the constant β/α for orthovoltage irradiation from these data is 2.9 x 10 -3 rad -1 for the cell line determining acute skin tolerance. A radiation isoeffect relationship, based on the quadratic cell survival curve, is introduced for human skin. This relationship has some advantages over the nominal standard dose (NSD). First, its use is not restricted to tolerance level reactions. Second, a modification of the relationship, which is also introduced, may be employed in the selection of doses per treatment when irradiation dose fractions are administered at short intervals where repair of sublethal injury is incomplete

  4. Thrombin impairs human endometrial endothelial angiogenesis; implications for progestin-only contraceptive-induced abnormal uterine bleeding.

    Science.gov (United States)

    Shapiro, John P; Guzeloglu-Kayisli, Ozlem; Kayisli, Umit A; Semerci, Nihan; Huang, S Joseph; Arlier, Sefa; Larsen, Kellie; Fadda, Paolo; Schatz, Frederick; Lockwood, Charles J

    2017-06-01

    Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by prothrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis. Liquid chromatography/tandem mass spectrometry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time-polymerase chain reaction (PCR) evaluated conditioned medium supernatant and cell lysates from control versus thrombin-treated HESCs. Pre- and post-Depo medroxyprogesterone acetate (DMPA)-administered endometria were immunostained for CSPG4. Proliferation, apoptosis and tube formation were assessed in human endometrial endothelial cells (HEECs) incubated with recombinant human (rh)-CSPG4 or thrombin or both. Thrombin induced CSPG4 protein expression in cultured HESCs as detected by mass spectrometry and ELISA (pabnormal uterine bleeding in DMPA users. Mass spectrometry analysis identified several HESC-secreted proteins regulated by thrombin. Therapeutic agents blocking angiogenic effects of thrombin in HESCs can prevent or minimize progestin-only contraceptive-induced abnormal uterine bleeding. Copyright © 2017. Published by Elsevier Inc.

  5. Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy.

    Science.gov (United States)

    Heusschen, Roy; Freitag, Nancy; Tirado-González, Irene; Barrientos, Gabriela; Moschansky, Petra; Muñoz-Fernández, Raquel; Leno-Durán, Ester; Klapp, Burghard F; Thijssen, Victor L J L; Blois, Sandra M

    2013-01-