Science.gov

Sample records for affect human activities

  1. ANALYSIS OF DISCRIMINATING FACTORS IN HUMAN ACTIVITIES THAT AFFECT EXPOSURE

    EPA Science Inventory

    Accurately modeling exposure to particulate matter (PM) and other pollutants ultimately involves the utilization of human location-activity databases to assist in understanding the potential variability of microenvironmental exposures. This paper critically considers and stati...

  2. Disturbances of electrodynamic activity affect abortion in human

    NASA Astrophysics Data System (ADS)

    Jandová, A.; Nedbalová, M.; Kobilková, J.; Čoček, A.; Dohnalová, A.; Cifra, M.; Pokorný, J.

    2011-12-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  3. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    PubMed

    Moreira-Arce, Dario; Vergara, Pablo M; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants

  4. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape

    PubMed Central

    Moreira-Arce, Dario; Vergara, Pablo M.; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants and

  5. Do human activities affect the picoplankton structure of the Ahe atoll lagoon (Tuamotu Archipelago, French Polynesia)?

    PubMed

    Bouvy, Marc; Dupuy, Christine; Pagano, Marc; Barani, Aude; Charpy, Loic

    2012-01-01

    The spatial variations of the picoplankton (photoautotrophic and heterotrophic microorganisms) in the Ahe atoll lagoon were studied in May and October 2008 to assess whether they were affected by human activities along the atoll. Spatial patterns were studied using 10 sampling stations chosen according to the location of the anthropogenic activities (pearl farming, harbor). Experiments were also carried out to determine whether bacterial growth, with or without predators, was limited by inorganic (N and P) substrates. The results showed that heterotrophic bacterioplankton abundance was superior to the photoautotrophic organisms, especially in May. Significant increases in bacterial abundance were observed in May after 24 h incubation with +P and +N (but not in October). All samples complied with the quality levels for fecal indicator bacteria (FIB) defined by the European Union and there was no evidence that human sewage had any impact on picoplankton over the whole atoll.

  6. Dissociation in human prefrontal cortex of affective influences on working memory-related activity.

    PubMed

    Perlstein, William M; Elbert, Thomas; Stenger, V Andrew

    2002-02-05

    Although neural activity associated with emotion is becoming better understood, the influence of affective parameters on brain activity reflecting cognitive functioning in humans remains poorly characterized. We examined affective influences on working memory (WM) and tested the hypotheses that (i) dorsolateral prefrontal cortex (DLPFC) activity reflecting WM is influenced by the emotion-evoking qualities of task-relevant stimuli, but only when brought "on-line" by task demands, and (ii) DLPFC and orbitofrontal cortex (OFC) activities are inversely related as a function of emotional valence. Participants performed two tasks while event-related functional MRI measured brain activity; one task required active maintenance of stimulus representations in WM, and the other task required target detection responses with no demand for WM. Stimuli were standardized emotional (pleasant and unpleasant) and neutral pictures. Emotional stimuli differentially influenced DPFC and OFC activity during WM; DLPFC was influenced by emotional valence, enhanced by pleasant and reduced by unpleasant, compared to neutral stimuli, only when task conditions required WM. OFC was valence-sensitive during both tasks, greater to arousing than neutral stimuli when WM demand was low and in inverse relationship to DLPFC with high WM demand. Further, DLPFC and OFC activities are inversely related with respect to emotional valence during the WM task. The results are consistent with the hypothesis that the intrinsic valence of task-relevant stimuli maintained in WM modulates DLPFC activity but only when the DLPFC is required for task demands. Findings suggest a conceptualization of DLPFC and its involvement in WM that takes into account a role for affective parameters.

  7. Low-frequency sound affects active micromechanics in the human inner ear.

    PubMed

    Kugler, Kathrin; Wiegrebe, Lutz; Grothe, Benedikt; Kössl, Manfred; Gürkov, Robert; Krause, Eike; Drexl, Markus

    2014-10-01

    Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing.

  8. Rapid and Quantitative Assay of Amyloid-Seeding Activity in Human Brains Affected with Prion Diseases

    PubMed Central

    Takatsuki, Hanae; Satoh, Katsuya; Sano, Kazunori; Fuse, Takayuki; Nakagaki, Takehiro; Mori, Tsuyoshi; Ishibashi, Daisuke; Mihara, Ban; Takao, Masaki; Iwasaki, Yasushi; Yoshida, Mari; Atarashi, Ryuichiro; Nishida, Noriyuki

    2015-01-01

    The infectious agents of the transmissible spongiform encephalopathies are composed of amyloidogenic prion protein, PrPSc. Real-time quaking-induced conversion can amplify very small amounts of PrPSc seeds in tissues/body fluids of patients or animals. Using this in vitro PrP-amyloid amplification assay, we quantitated the seeding activity of affected human brains. End-point assay using serially diluted brain homogenates of sporadic Creutzfeldt–Jakob disease patients demonstrated that 50% seeding dose (SD50) is reached approximately 1010/g brain (values varies 108.79–10.63/g). A genetic case (GSS-P102L) yielded a similar level of seeding activity in an autopsy brain sample. The range of PrPSc concentrations in the samples, determined by dot-blot assay, was 0.6–5.4 μg/g brain; therefore, we estimated that 1 SD50 unit was equivalent to 0.06–0.27 fg of PrPSc. The SD50 values of the affected brains dropped more than three orders of magnitude after autoclaving at 121°C. This new method for quantitation of human prion activity provides a new way to reduce the risk of iatrogenic prion transmission. PMID:26070208

  9. 4-Methylthiobutyl isothiocyanate (Erucin) from rocket plant dichotomously affects the activity of human immunocompetent cells.

    PubMed

    Gründemann, Carsten; Garcia-Käufer, Manuel; Lamy, Evelyn; Hanschen, Franziska S; Huber, Roman

    2015-03-15

    Isothiocyanates (ITC) from the Brassicaceae plant family are regarded as promising for prevention and treatment of cancer. However, experimental settings consider their therapeutic action without taking into account the risk of unwanted effects on healthy tissues. In the present study we investigated the effects of Eruca sativa seed extract containing MTBITC (Erucin) and pure Erucin from rocket plant on healthy cells of the human immune system in vitro. Hereby, high doses of the plant extract as well as of Erucin inhibited cell viability of human lymphocytes via induction of apoptosis to comparable amounts. Non-toxic low concentrations of the plant extract and pure Erucin altered the expression of the interleukin (IL)-2 receptor but did not affect further T cell activation, proliferation and the release of the effector molecules interferon (IFN)-gamma and IL-2 of T-lymphocytes. However, the activity of NK-cells was significantly reduced by non-toxic concentrations of the plant extract and pure Erucin. These results indicate that the plant extract and pure Erucin interfere with the function of human T lymphocytes and decreases the activity of NK-cells in comparable concentrations. Long-term clinical studies with ITC-enriched plant extracts from Brassicaceae should take this into account.

  10. PMCA activity and membrane tubulin affect deformability of erythrocytes from normal and hypertensive human subjects.

    PubMed

    Monesterolo, Noelia E; Nigra, Ayelen D; Campetelli, Alexis N; Santander, Verónica S; Rivelli, Juan F; Arce, Carlos A; Casale, Cesar H

    2015-11-01

    Our previous studies demonstrated formation of a complex between acetylated tubulin and brain plasma membrane Ca(2+)-ATPase (PMCA), and the effect of the lipid environment on structure of this complex and on PMCA activity. Deformability of erythrocytes from hypertensive human subjects was reduced by an increase in membrane tubulin content. In the present study, we examined the regulation of PMCA activity by tubulin in normotensive and hypertensive erythrocytes, and the effect of exogenously added diacylglycerol (DAG) and phosphatidic acid (PA) on erythrocyte deformability. Some of the key findings were that: (i) PMCA was associated with tubulin in normotensive and hypertensive erythrocytes, (ii) PMCA enzyme activity was directly correlated with erythrocyte deformability, and (iii) when tubulin was present in the erythrocyte membrane, treatment with DAG or PA led to increased deformability and associated PMCA activity. Taken together, our findings indicate that PMCA activity is involved in deformability of both normotensive and hypertensive erythrocytes. This rheological property of erythrocytes is affected by acetylated tubulin and its lipid environment because both regulate PMCA activity.

  11. 50 Hz sinusoidal magnetic fields do not affect human lymphocyte activation and proliferation in vitro

    NASA Astrophysics Data System (ADS)

    Capri, Miriam; Mesirca, Pietro; Remondini, Daniel; Carosella, Simona; Pasi, Sara; Castellani, Gastone; Franceschi, Claudio; Bersani, Ferdinando

    2004-12-01

    In the last 30 years, an increasing public concern about the possible harmful effects of electromagnetic fields generated by power lines and domestic appliances has pushed the scientific community to search for a correct and comprehensive answer to this problem. In this work the effects of exposure to 50 Hz sinusoidal magnetic fields, with a magnetic flux density of 0.05 mT and 2.5 mT (peak values), were studied on human peripheral blood mononuclear cells (PBMCs) collected from healthy young and elderly donors. Cell activation and proliferation were investigated by using flow cytometry techniques and 3H-TdR incorporation assays, respectively. The results obtained indicated that exposure to the fields altered neither DNA synthesis nor the capacity of lymphocytes to enter the activation phase and progress into the cell cycle. Thus, the conclusions are that two important functional phases of human lymphocytes, such as activation and proliferation, are not affected by exposures to 50 Hz magnetic fields similar to those found under power lines.

  12. Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.

    PubMed

    Liu, Wanqing; Ramírez, Jacqueline; Gamazon, Eric R; Mirkov, Snezana; Chen, Peixian; Wu, Kehua; Sun, Chang; Cox, Nancy J; Cook, Edwin; Das, Soma; Ratain, Mark J

    2014-10-15

    The aim of this study was to discover cis- and trans-acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28 and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these UGTs were quantified. We found that UGT expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74-217% and 52%, 39-105%, respectively). CAR, PXR and ESR1 were found to be the most important trans-regulators of UGT transcription (median and range of correlation coefficients: 46%, 6-58%; 47%, 9-58%; and 52%, 24-75%, respectively). Hepatic UGT activities were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted P < 0.05) associated with mRNA expression and/or activities of UGT1A1, UGT1A3 and UGT2B17. We found novel SNPs in the UGT2B17 CNV region accounting for variability in UGT2B17 gene transcription and testosterone glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs.

  13. Food Affects Human Behavior.

    ERIC Educational Resources Information Center

    Kolata, Gina

    1982-01-01

    A conference on whether food and nutrients affect human behavior was held on November 9, 1982 at the Massachusetts Institute of Technology. Various research studies on this topic are reviewed, including the effects of food on brain biochemistry (particularly sleep) and effects of tryptophane as a pain reducer. (JN)

  14. Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells.

    PubMed

    Gosset, P; Charbonnier, A S; Delerive, P; Fontaine, J; Staels, B; Pestel, J; Tonnel, A B; Trottein, F

    2001-10-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma ), a member of the nuclear receptor superfamily, has recently been described as a modulator of macrophage functions and as an inhibitor of T cell proliferation. Here, we investigated the role of PPARgamma in dendritic cells (DC), the most potent antigen-presenting cells. We showed that PPARgamma is highly expressed in immature human monocyte-derived DC (MDDC) and that it may affect the immunostimulatory function of MDDC stimulated with lipopolysaccharide (LPS) or via CD40 ligand (CD40L). We found that the synthetic PPARgamma agonist rosiglitazone (as well as pioglitazone and troglitazone) significantly increases on LPS- and CD40L-activated MDDC, the surface expression of CD36 (by 184% and 104%, respectively) and CD86 (by 54% and 48%), whereas it reduces the synthesis of CD80 (by 42% and 42%). Moreover, activation of PPARgamma resulted in a dramatic decreased secretion of the Th1-promoting factor IL-12 in LPS- and CD40L-stimulated cells (by 47% and 62%), while the production of IL-1beta, TNF-alpha, IL-6 and IL-10 was unaffected. Finally, PPARgamma ligands down-modulate the synthesis of IFN-gamma -inducible protein-10 (recently termed as CXCL10) and RANTES (CCL5), both chemokines involved in the recruitment of Th1 lymphocytes (by 49% and 30%), but not the levels of the Th2 cell-attracting chemokines,macrophage-derived chemokine (CCL22) and thymus and activation regulated chemokine (CCL17), in mature MDDC. Taken together, our data suggest that activation of PPARgamma in human DC may have an impact in the orientation of primary and secondary immune responses by favoring type 2 responses.

  15. Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide.

    PubMed Central

    Amin, A R; Attur, M; Patel, R N; Thakker, G D; Marshall, P J; Rediske, J; Stuchin, S A; Patel, I R; Abramson, S B

    1997-01-01

    Cartilage specimens from osteoarthritis (OA)-affected patients spontaneously released PGE2 at 48 h in ex vivo culture at levels at least 50-fold higher than in normal cartilage and 18-fold higher than in normal cartilage + cytokines + endotoxin. The superinduction of PGE2 production coincides with the upregulation of cyclooxygenase-2 (COX-2) in OA-affected cartilage. Production of both nitric oxide (NO) and PGE2 by OA cartilage explants is regulated at the level of transcription and translation. Dexamethasone inhibited only the spontaneously released PGE2 production, and not NO, in OA-affected cartilage. The NO synthase inhibitor HN(G)-monomethyl-L-arginine monoacetate inhibited OA cartilage NO production by > 90%, but augmented significantly (twofold) the spontaneous production of PGE2 in the same explants. Similarly, addition of exogenous NO donors to OA cartilage significantly inhibited PGE2 production. Cytokine + endotoxin stimulation of OA explants increased PGE2 production above the spontaneous release. Addition of L-NMMA further augmented cytokine-induced PGE2 production by at least fourfold. Inhibition of PGE2 by COX-2 inhibitors (dexamethasone or indomethacin) or addition of exogenous PGE2 did not significantly affect the spontaneous NO production. These data indicate that human OA-affected cartilage in ex vivo conditions shows (a) superinduction of PGE2 due to upregulation of COX-2, and (b) spontaneous release of NO that acts as an autacoid to attenuate the production of the COX-2 products such as PGE2. These studies, together with others, also suggest that PGE2 may be differentially regulated in normal and OA-affected chondrocytes. PMID:9077531

  16. Nutritional status affects branched-chain oxoacid dehydrogenase activity during exercise in humans.

    PubMed

    Jackman, M L; Gibala, M J; Hultman, E; Graham, T E

    1997-02-01

    We examined the effect of glycogen availability and branched-chain amino acid (BCAA) supplementation on branched-chain oxoacid dehydrogenase (BCOAD) activity during exercise. Six subjects cycled at approximately 75% of their maximal oxygen uptake to exhaustion on three occasions under different preexercise conditions: 1) low muscle glycogen (LOW), 2) low muscle glycogen plus BCAA supplementation (LOW+BCAA), and 3) high muscle glycogen (CON). The LOW trial was performed first, followed by the other two conditions in random order, and biopsies for all trials were obtained at rest, after 15 min of exercise (15 min), and at the point of exhaustion during the LOW trial (49 min). BCOAD activity was not different among the three conditions at rest; however, at 15 min BCOAD activity was higher (P < or = 0.05) for the LOW (31 +/- 5%) and LOW+BCAA (43 +/- 11%) conditions compared with CON (12 +/- 1%). BCOAD activity at 49 min was not different from respective values at 15 min for any condition. These data indicate that BCOAD is rapidly activated during submaximal exercise under conditions associated with low carbohydrate availability. However, there was no relationship between BCOAD activity and glycogen concentration or net glycogenolysis, which suggests that factors other than glycogen availability are important for BCOAD regulation during exercise in humans.

  17. Neural networks to simulate regional ground water levels affected by human activities.

    PubMed

    Feng, Shaoyuan; Kang, Shaozhong; Huo, Zailin; Chen, Shaojun; Mao, Xiaomin

    2008-01-01

    In arid regions, human activities like agriculture and industry often require large ground water extractions. Under these circumstances, appropriate ground water management policies are essential for preventing aquifer overdraft, and thereby protecting critical ecologic and economic objectives. Identification of such policies requires accurate simulation capability of the ground water system in response to hydrological, meteorological, and human factors. In this research, artificial neural networks (ANNs) were developed and applied to investigate the effects of these factors on ground water levels in the Minqin oasis, located in the lower reach of Shiyang River Basin, in Northwest China. Using data spanning 1980 through 1997, two ANNs were developed to model and simulate dynamic ground water levels for the two subregions of Xinhe and Xiqu. The ANN models achieved high predictive accuracy, validating to 0.37 m or less mean absolute error. Sensitivity analyses were conducted with the models demonstrating that agricultural ground water extraction for irrigation is the predominant factor responsible for declining ground water levels exacerbated by a reduction in regional surface water inflows. ANN simulations indicate that it is necessary to reduce the size of the irrigation area to mitigate ground water level declines in the oasis. Unlike previous research, this study demonstrates that ANN modeling can capture important temporally and spatially distributed human factors like agricultural practices and water extraction patterns on a regional basin (or subbasin) scale, providing both high-accuracy prediction capability and enhanced understanding of the critical factors influencing regional ground water conditions.

  18. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase.

    PubMed

    Schweiger, Martina; Paar, Margret; Eder, Christina; Brandis, Janina; Moser, Elena; Gorkiewicz, Gregor; Grond, Susanne; Radner, Franz P W; Cerk, Ines; Cornaciu, Irina; Oberer, Monika; Kersten, Sander; Zechner, Rudolf; Zimmermann, Robert; Lass, Achim

    2012-11-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL), which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 switch gene-2 (G0S2). CGI-58 activates and G0S2 inhibits ATGL activity. In contrast to mice, the functional role of G0S2 in human adipocyte lipolysis is poorly characterized. Here we show that overexpression or silencing of G0S2 in human SGBS adipocytes decreases and increases lipolysis, respectively. Human G0S2 is upregulated during adipocyte differentiation and inhibits ATGL activity in a dose-dependent manner. Interestingly, C-terminally truncated ATGL mutants, which fail to localize to lipid droplets, translocate to the lipid droplet upon coexpression with G0S2, suggesting that G0S2 anchors ATGL to lipid droplets independent of ATGL's C-terminal lipid binding domain. Taken together, our results indicate that G0S2 also regulates human lipolysis by affecting enzyme activity and intracellular localization of ATGL. Increased lipolysis is known to contribute to the pathogenesis of insulin resistance, and G0S2 expression has been shown to be reduced in poorly controlled type 2 diabetic patients. Our data indicate that downregulation of G0S2 in adipose tissue could represent one of the underlying causes leading to increased lipolysis in the insulin-resistant state.

  19. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    PubMed Central

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  20. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    PubMed

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  1. Physical activity affects plasma coenzyme Q10 levels differently in young and old humans.

    PubMed

    Del Pozo-Cruz, Jesús; Rodríguez-Bies, Elisabet; Ballesteros-Simarro, Manuel; Navas-Enamorado, Ignacio; Tung, Bui Thanh; Navas, Plácido; López-Lluch, Guillermo

    2014-04-01

    Coenzyme Q (Q) is a key lipidic compound for cell bioenergetics and membrane antioxidant activities. It has been shown that also has a central role in the prevention of oxidation of plasma lipoproteins. Q has been associated with the prevention of cholesterol oxidation and several aging-related diseases. However, to date no clear data on the levels of plasma Q during aging are available. We have measured the levels of plasmatic Q10 and cholesterol in young and old individuals showing different degrees of physical activity. Our results indicate that plasma Q10 levels in old people are higher that the levels found in young people. Our analysis also indicates that there is no a relationship between the degree of physical activity and Q10 levels when the general population is studied. However, very interestingly, we have found a different tendency between Q10 levels and physical activity depending on the age of individuals. In young people, higher activity correlates with lower Q10 levels in plasma whereas in older adults this ratio changes and higher activity is related to higher plasma Q10 levels and higher Q10/Chol ratios. Higher Q10 levels in plasma are related to lower lipoperoxidation and oxidized LDL levels in elderly people. Our results highlight the importance of life habits in the analysis of Q10 in plasma and indicate that the practice of physical activity at old age can improve antioxidant capacity in plasma and help to prevent cardiovascular diseases.

  2. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    SciTech Connect

    Not Available

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  3. Verbal working memory load affects prefrontal cortices activation: evidence from a functional NIRS study in humans

    NASA Astrophysics Data System (ADS)

    Li, Chengjun; Gong, Hui; Zeng, Shaoqun; Luo, Qingming

    2005-03-01

    Working memory (WM) refers to the temporary maintenance of information that is no longer accessible in the environment, and the manipulation of this information for subsequent use. PET and functional MRI studies suggest that prefrontal cortex (PFC) is involved in WM. Here, we report a functional near-infrared spectroscopy (NIRS) study on the PFC activation caused by a WM task, a verbal n-back task. During performance of the task, concentration changes of oxy-Hb (HbO2), deoxy-Hb (Hb), and total-Hb (HbT) in subjects" prefrontal cortex were monitored by a 24-channel functional NIRS imager. The behavioral performances (accuracy and response time) were recorded simultaneously. Results revealed that as memory load increased, subjects showed poorer behavioral performance as well as monotonously increasing magnitudes of the activations in the left ventrolateral PFC (VLPFC) and bilateral dorsolateral PFC (DLPFC). In addition, the analysis of comparison between subjects showed that certain relations likely exist between the cerebral activation and the performance parameters for an individual subject: lower accuracy is accompanied by longer response time and further activation. Such means that the subject with difficulty in solving a problem will demonstrate more significant hemodynamic changes compared with the subject without difficulty in solving the same problem.

  4. The osteogenic activity of human mandibular fracture haematoma-derived progenitor cells is affected by bisphosphonate in vitro.

    PubMed

    Imai, Y; Hasegawa, T; Takeda, D; Akashi, M; Komori, T

    2015-03-01

    It is known that bisphosphonates (BPs) suppress the activity of osteoclasts; however, it has not been reported whether BPs affect the potential of human mandibular fracture haematoma-derived cells (MHCs) for bone differentiation. In this study, we examined whether the degree of bone differentiation changes following the administration of BP in vitro. The effects of alendronate and risedronate (10(-8) to 10(-7)M (mol/l)) on cell proliferation were evaluated at 4 and 8 days, after which BP treatment was applied for 4, 8, 14, and 20 days prior to assessing the alkaline phosphatase (ALP) activity and performing the mineralization assay. Alendronate 10(-8) and 10(-7)M and risedronate 10(-7)M decreased the degree of cell proliferation on day 8 (P<0.05). Using an ELISA, the ALP activity of the control, alendronate 10(-8)M, risedronate 10(-8)M, and risedronate 10(-7)M groups were 112.1±10.2%, 156.1±24.3%, 138.8±16.5%, and 133.3±10.3%, respectively, at 14 days after treatment (day 0 in each group was considered to be 100%). ALP activity was significantly higher in the alendronate 10(-8)M and risedronate 10(-8) and 10(-7)M groups than in the control group (P=0.010, 0.014, and 0.009, respectively). It is possible that BPs increase the potential of MHCs for osteogenic differentiation depending on the concentration of the drug.

  5. Human cerebral response to animal affective vocalizations.

    PubMed

    Belin, Pascal; Fecteau, Shirley; Charest, Ian; Nicastro, Nicholas; Hauser, Marc D; Armony, Jorge L

    2008-03-07

    It is presently unknown whether our response to affective vocalizations is specific to those generated by humans or more universal, triggered by emotionally matched vocalizations generated by other species. Here, we used functional magnetic resonance imaging in normal participants to measure cerebral activity during auditory stimulation with affectively valenced animal vocalizations, some familiar (cats) and others not (rhesus monkeys). Positively versus negatively valenced vocalizations from cats and monkeys elicited different cerebral responses despite the participants' inability to differentiate the valence of these animal vocalizations by overt behavioural responses. Moreover, the comparison with human non-speech affective vocalizations revealed a common response to the valence in orbitofrontal cortex, a key component on the limbic system. These findings suggest that the neural mechanisms involved in processing human affective vocalizations may be recruited by heterospecific affective vocalizations at an unconscious level, supporting claims of shared emotional systems across species.

  6. Brain activation related to affective dimension during thermal stimulation in humans: a functional magnetic resonance imaging study.

    PubMed

    Sung, Eun-Jung; Yoo, Seung-Schik; Yoon, Hyo Woon; Oh, Sung-Suk; Han, Yeji; Park, Hyun Wook

    2007-07-01

    The aim of this study was to identify the activated brain region that is involved with the affective dimension of thermal stimulation (not pain, but innocuous warming) using functional MR imaging. Twelve healthy, right-handed male subjects participated in the study. Thermal stimulation with two different temperatures of 41 degrees C and 34 degrees C was applied to the subjects using a fomentation pack, wrapped around the right lower leg of each subject. On the basis of the subjects' responses after the scanning sessions, the authors were able to observe that the subjects felt "warm" and "slightly pleasant and comfortable" under the 41 degrees C condition. The experimental results indicated that warm stimulation produced a significant increase of activation compared to thermal neutral stimulation in various regions such as contralateral insular, ipsilateral cerebellum, ipsilateral putamen, contralateral middle frontal gyrus, ipsilateral inferior frontal gyrus, contralateral postcentral gyrus, and contralateral paracentral lobule. The activated regions are known to be related to thermal sensory, affective/emotional awareness, cognitive functions, sensory-discrimination, and emotion/affective processing, and so on. These results suggest that an appropriate thermal stimulation can produce a positive emotion and activate emotion/affect related regions of the brain.

  7. Alpha7-nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: role of mitogen-activated protein kinase pathway.

    PubMed

    Trombino, Sonya; Cesario, Alfredo; Margaritora, Stefano; Granone, PierLuigi; Motta, Giovanni; Falugi, Carla; Russo, Patrizia

    2004-01-01

    This study presents data suggesting that both human mesothelioma (cell lines and human mesothelioma biopsies) and human normal mesothelial cells express receptors for acetylcholine and that stimulation of these receptors by nicotine prompted cell growth via activation of nicotinic cholinergic receptors. Thus, these data demonstrate that: (a) human mesothelioma cells and human biopsies of mesothelioma as well as of normal pleural mesothelial cells express functionally alpha-7 nicotinic acethlycholine receptors, evaluated by alpha-bungarotoxin-FITC binding, receptor binding assay, Western blot, and reverse transcription-PCR; (b) choline acetyltransferase immunostaining is present in mesothelioma cells; (c) mesothelioma cell growth is modulated by the cholinergic system in which agonists (i.e., nicotine) has a proliferative effect, and antagonists (i.e., curare) has an inhibitory effect, evaluated by cell cloning, DNA synthesis and cell cycle; (d) nicotine induces Ca(+2) influx, evaluated by [(45)Ca(2+)] uptake, and consequently activation of mitogen-activated protein kinase pathway (extracellular signal-regulated kinase and p90(RSK) phosphorylation), evaluated by Western blot; and (e) apoptosis mechanisms in mesothelioma cells are under the control of the cholinergic system (nicotine antiapoptotic via induction of nuclear factor-kappaB complexes and phosphorylation of Bad at Ser(112); curare proapoptotic via G(0)-G(1) arrest p21(waf-1) dependent but p53 independent). The involvement of the nonneuronal cholinergic system in mesothelioma appears reasonable and open up new therapeutic strategies.

  8. Active site mutant transgene confers tolerance to human β-glucuronidase without affecting the phenotype of MPS VII mice

    PubMed Central

    Sly, William S.; Vogler, Carole; Grubb, Jeffrey H.; Zhou, Mi; Jiang, Jinxing; Zhou, Xiao Yan; Tomatsu, Shunji; Bi, Yanhua; Snella, Elizabeth M.

    2001-01-01

    Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an autosomal recessive lysosomal storage disorder due to an inherited deficiency of β-glucuronidase. A naturally occurring mouse model for this disease was discovered at The Jackson Laboratory and shown to be due to homozygosity for a 1-bp deletion in exon 10 of the gus gene. The murine model MPS VII (gusmps/mps) has been very well characterized and used extensively to evaluate experimental strategies for lysosomal storage diseases, including bone marrow transplantation, enzyme replacement therapy, and gene therapy. To enhance the value of this model for enzyme and gene therapy, we produced a transgenic mouse expressing the human β-glucuronidase cDNA with an amino acid substitution at the active site nucleophile (E540A) and bred it onto the MPS VII (gusmps/mps) background. We demonstrate here that the mutant mice bearing the active site mutant human transgene retain the clinical, morphological, biochemical, and histopathological characteristics of the original MPS VII (gusmps/mps) mouse. However, they are now tolerant to immune challenge with human β-glucuronidase. This “tolerant MPS VII mouse model” should be useful for preclinical trials evaluating the effectiveness of enzyme and/or gene therapy with the human gene products likely to be administered to human patients with MPS VII. PMID:11226217

  9. Active site mutant transgene confers tolerance to human beta-glucuronidase without affecting the phenotype of MPS VII mice.

    PubMed

    Sly, W S; Vogler, C; Grubb, J H; Zhou, M; Jiang, J; Zhou, X Y; Tomatsu, S; Bi, Y; Snella, E M

    2001-02-27

    Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an autosomal recessive lysosomal storage disorder due to an inherited deficiency of beta-glucuronidase. A naturally occurring mouse model for this disease was discovered at The Jackson Laboratory and shown to be due to homozygosity for a 1-bp deletion in exon 10 of the gus gene. The murine model MPS VII (gus(mps/mps)) has been very well characterized and used extensively to evaluate experimental strategies for lysosomal storage diseases, including bone marrow transplantation, enzyme replacement therapy, and gene therapy. To enhance the value of this model for enzyme and gene therapy, we produced a transgenic mouse expressing the human beta-glucuronidase cDNA with an amino acid substitution at the active site nucleophile (E540A) and bred it onto the MPS VII (gus(mps/mps)) background. We demonstrate here that the mutant mice bearing the active site mutant human transgene retain the clinical, morphological, biochemical, and histopathological characteristics of the original MPS VII (gus(mps/mps)) mouse. However, they are now tolerant to immune challenge with human beta-glucuronidase. This "tolerant MPS VII mouse model" should be useful for preclinical trials evaluating the effectiveness of enzyme and/or gene therapy with the human gene products likely to be administered to human patients with MPS VII.

  10. Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes

    SciTech Connect

    Lynch, Caitlin; Pan, Yongmei; Li, Linhao; Heyward, Scott; Moeller, Timothy; Swaan, Peter W.; Wang, Hongbing

    2014-08-15

    Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods: Ligand-based structure–activity models were used for virtual screening of the Specs database ( (www.specs.net)) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results: Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fatty acid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion: Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fatty acid synthesis. Implications: Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. - Highlights: • Novel hCAR activators were identified by computational and biological approaches. • The role

  11. Priming affects the activity of a specific region of the promoter of the human beta interferon gene.

    PubMed Central

    Dron, M; Lacasa, M; Tovey, M G

    1990-01-01

    Treatment of Daudi or HeLa cells with human interferon (IFN) alpha 8 before induction with either poly(I)-poly(C) or Sendai virus resulted in an 8- to 100-fold increase in IFN production. The extent of priming in Daudi cells paralleled the increase in the intracellular content of IFN-beta mRNA. IFN-alpha mRNA remained undetectable in poly(I)-poly(C)-treated Daudi cells either before or after priming. An IFN-resistant clone of Daudi cells was found to produce 4- to 20-fold more IFN after priming, indicating that priming was unrelated to the phenotype of IFN sensitivity. IFN treatment of either Daudi or HeLa cells transfected with the human IFN-beta promoter (-282 to -37) linked to the chloramphenicol acetyltransferase (CAT) gene resulted in an increase in CAT activity after induction with poly(I)-poly(C) or Sendai virus. A synthetic double-stranded oligonucleotide corresponding to an authentic 30-base-pair (bp) region of the human IFN-beta promoter between positions -91 and -62 was found to confer virus inducibility upon the reporter CAT gene in HeLa cells. IFN treatment of HeLa cells transfected with this 30-bp region of the IFN-beta promoter in either the correct or reversed orientation also increased CAT activity upon subsequent induction. IFN treatment alone had no detectable effect on the activity of either the 30-bp region or the complete human IFN promoter. Images PMID:2153928

  12. Musical expertise affects attention as reflected by auditory-evoked gamma-band activity in human EEG.

    PubMed

    Ott, Cyrill G M; Stier, Christina; Herrmann, Christoph S; Jäncke, Lutz

    2013-06-19

    Musical expertise has been shown to induce widespread structural and functional alterations in the brain, even-handedly affecting top-down and bottom-up factors. At the same time, it is known that the early evoked gamma-band response (GBR) can be modulated by top-down as well as bottom-up factors such as attention and sound intensity. In this study, we examined the effects of musicianship and attention on the intensity modulation of the auditory-evoked GBR. We compared the electroencephalogram of 17 professional musicians with that of 17 musical laymen obtained during either a forced-choice discrimination task (active) or a passive listening condition. Pure 1000 Hz sine tones were presented at three systematically varied sound intensities (40, 60, and 80 dB sound pressure levels). The results of auditory-evoked potentials and evoked GBRs obtained in the active condition predominantly corresponded to the findings of previous studies. Besides the already known augmentation of the early evoked GBR because of enhanced intertrial phase coherence with increasing sound intensity, we also observed stronger GBRs and enhanced phase locking under the active condition compared with passive listening, whereas the general shape of intensity modulation was comparable between the two conditions. In addition, phase locking to stimulus onset was increased for stimuli of all three intensities when attended, whereas in musicians, only stimuli of the highest intensity (80 dB) induced significantly increased phase locking under the active condition. Taken together, our results suggest that musical expertise influences attention effects on the intensity-modulated early auditory-evoked GBR with respect to intertrial phase coherence.

  13. Water immersion to the femur level affects cerebral cortical activity in humans: functional near-infrared spectroscopy study.

    PubMed

    Sato, Daisuke; Onishi, Hideaki; Yamashiro, Koya; Iwabe, Tatsuya; Shimoyama, Yoshimitsu; Maruyama, Atsuo

    2012-04-01

    Water immersion is widely used in physiotherapy and may even improve the functional outcomes of hemiplegic patients after stroke. To investigate the cortical responses to water immersion, functional near-infrared spectroscopy (fNIRS) was used to measure cortical activations in the primary somatosensory area (S1), parietal association area (PAA), supplementary motor area (SMA), and primary motor area (M1). Nine healthy adult males were rested in a sitting position for 15 min with simultaneous measurements of fNIRS, blood pressure, and skin temperature. The fNIRS signal and other physiological parameters were measured under three conditions, the non-immersed condition (baseline control), as the immersion tank was filling with water (pouring water condition), and during sustained water immersion. Each condition lasted for 5 min. The water level was allowed to reach the femur, and during the experiment, room and water temperatures were maintained at 34°C. Oxygenated hemoglobin (oxyHb) concentrations in the S1, PAA, SMA, and M1 remained stable during baseline recording but gradually increased during water pouring and immersion. Significantly higher oxyHb levels were observed in S1 at 20 s after the onset of water immersion condition and in the PAA at 40 s. Subsequently, oxyHb levels in the SMA and M1 increased significantly 100 s after the onset of water immersion condition. In contrast, no significant changes in blood pressure, heart rate, or skin temperature were observed. Water immersion resulted in increased activity in both sensory and motor areas of cortex as measured by non-invasive fNIRS. Water immersion may enhance the efficacy of physical therapy by providing background activation to affected areas of the cortex, thereby enhancing signal processing and learning.

  14. Stimulus intensity affects early sensory processing: sound intensity modulates auditory evoked gamma-band activity in human EEG.

    PubMed

    Schadow, Jeanette; Lenz, Daniel; Thaerig, Stefanie; Busch, Niko A; Fründ, Ingo; Herrmann, Christoph S

    2007-08-01

    We studied the effect of different sound intensities on the auditory evoked gamma-band response (GBR). Previous studies observed oscillatory gamma activity in the auditory cortex of animals and humans. For the visual modality, it has been demonstrated that the GBR can be modulated by top-down (attention, memory) as well as bottom-up factors (stimulus properties). Therefore, we expected to find a sound intensity modulation for the auditory GBR. 21 healthy participants without hearing deficits were investigated in a forced-choice discrimination task. Sinusoidal tones were presented at three systematically varied sound intensities (30, 45, 60 dB hearing level). The results of the auditory evoked potentials were predominantly consistent with previous studies. Furthermore, we observed an augmentation of the evoked GBR with increasing sound intensity. The analysis indicated that this intensity difference in the GBR amplitude most likely arises from increased phase-locking. The results demonstrate a distinct dependency between sound intensity and gamma-band oscillations. Future experiments that investigate the relationship between auditory evoked GBRs and higher cognitive processes should therefore select stimuli with an adequate sound intensity and control this variable to avoid confounding effects. In addition, it seems that gamma-band activity is more sensitive to exogenous stimulus parameters than evoked potentials.

  15. Satellite cell activity is differentially affected by contraction mode in human muscle following a work-matched bout of exercise

    PubMed Central

    Hyldahl, Robert D.; Olson, Ty; Welling, Tyson; Groscost, Logan; Parcell, Allen C.

    2014-01-01

    Optimal repair and adaptation of skeletal muscle is facilitated by resident stem cells (satellite cells). To understand how different exercise modes influence satellite cell dynamics, we measured satellite cell activity in conjunction with markers of muscle damage and inflammation in human skeletal muscle following a single work- and intensity-matched bout of eccentric (ECC) or concentric contractions (CON). Participants completed a single bout of ECC (n = 7) or CON (n = 7) of the knee extensors. A muscle biopsy was obtained before and 24 h after exercise. Functional measures and immunohistochemical analyses were used to determine the extent of muscle damage and indices of satellite cell activity. Cytokine concentrations were measured using a multiplexed magnetic bead assay. Isokinetic peak torque decreased following ECC (p < 0.05) but not CON. Greater histological staining of the damage marker Xin was observed in muscle samples of ECC vs. CON. Tenasin C immunoreactivity increased 15 fold (p < 0.01) following ECC and was unchanged following CON. The inflammatory cytokines interferon gamma-induced protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) increased pre- to post-ECC (4.26 ± 1.4 vs. 10.49 ± 5.8 pg/ml, and 3.06 ± 0.7 vs. 6.25 ± 4.6 pg/ml, respectively; p < 0.05). There was no change in any cytokine post-CON. Satellite cell content increased 27% pre- to post-ECC (0.10 ± 0.031 vs. 0.127 ± 0.041, respectively; p < 0.05). There was no change in satellite cell number in CON (0.099 ± 0.027 vs. 0.102 ± 0.029, respectively). There was no fiber type-specific satellite cell response following either exercise mode. ECC but not CON resulted in an increase in MyoD positive nuclei per myofiber pre- to post-exercise (p < 0.05), but there was no change in MyoD DNA binding activity in either condition. In conclusion, ECC but not CON results in functional and histological evidence of muscle damage that is accompanied by increased satellite cell activity 24 h

  16. Chemical form of selenium affects its uptake, transport and glutathione peroxidase activity in the human intestinal Caco-2 cell model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Determining the effect of selenium (Se) chemical form on uptake and transport in human intestinal cells is critical to assess Se bioavailability. In the present study, we measured the uptake and transport of various Se compounds in the human intestinal Caco-2 cell model. We found that two sources...

  17. Arthropods affecting the human eye.

    PubMed

    Panadero-Fontán, Rosario; Otranto, Domenico

    2015-02-28

    Ocular infestations by arthropods consist in the parasitization of the human eye, either directly (e.g., some insect larvae causing ophthalmomyiasis) or via arthropods feeding on lachrymal/conjunctival secretions (e.g., some eye-seeking insects, which also act as vectors of eye pathogens). In addition, demodicosis and phthiriasis may also cause eye discomfort in humans. Ophthalmomyiasis by larvae of the families Oestridae, Calliphoridae and Sarcophagidae, are frequent causative agents of human ocular infestations. Over the last decades, the extensive use of macrocyclic lactones in cattle has reduced the frequency of infestations by Hypoderma bovis and Hypoderma lineatum (family Oestridae), and consequently, human infestations by these species. A prompt diagnosis of ocular myiasis (e.g., by serological tests) is pivotal for positive prognoses, particularly when the larvae are not detectable during the ophthalmologic examination. Molecular diagnoses may also assist physicians and parasitologists in achieving time-efficient diagnoses of infestations by Oestridae causing myiasis. Finally, due to widespread international travel to exotic destinations, cases of myiasis are increasing in non-endemic areas, therefore requiring physicians to acquire a profound knowledge of the clinical symptoms linked to these infestations to prevent costly, inappropriate treatments or severe complications.

  18. Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

    PubMed Central

    Abooali, Maryam; Yasinska, Inna M.; Casely-Hayford, Maxwell A.; Berger, Steffen M.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.

    2015-01-01

    Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells. PMID:26384306

  19. Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity.

    PubMed

    Gibbs, Bernhard F; Gonçalves Silva, Isabel; Prokhorov, Alexandr; Abooali, Maryam; Yasinska, Inna M; Casely-Hayford, Maxwell A; Berger, Steffen M; Fasler-Kan, Elizaveta; Sumbayev, Vadim V

    2015-10-06

    Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells.

  20. Coriandrum sativum L. (Coriander) essential oil: antifungal activity and mode of action on Candida spp., and molecular targets affected in human whole-genome expression.

    PubMed

    Freires, Irlan de Almeida; Murata, Ramiro Mendonça; Furletti, Vivian Fernandes; Sartoratto, Adilson; Alencar, Severino Matias de; Figueira, Glyn Mara; de Oliveira Rodrigues, Janaina Aparecida; Duarte, Marta Cristina Teixeira; Rosalen, Pedro Luiz

    2014-01-01

    Oral candidiasis is an opportunistic fungal infection of the oral cavity with increasingly worldwide prevalence and incidence rates. Novel specifically-targeted strategies to manage this ailment have been proposed using essential oils (EO) known to have antifungal properties. In this study, we aim to investigate the antifungal activity and mode of action of the EO from Coriandrum sativum L. (coriander) leaves on Candida spp. In addition, we detected the molecular targets affected in whole-genome expression in human cells. The EO phytochemical profile indicates monoterpenes and sesquiterpenes as major components, which are likely to negatively impact the viability of yeast cells. There seems to be a synergistic activity of the EO chemical compounds as their isolation into fractions led to a decreased antimicrobial effect. C. sativum EO may bind to membrane ergosterol, increasing ionic permeability and causing membrane damage leading to cell death, but it does not act on cell wall biosynthesis-related pathways. This mode of action is illustrated by photomicrographs showing disruption in biofilm integrity caused by the EO at varied concentrations. The EO also inhibited Candida biofilm adherence to a polystyrene substrate at low concentrations, and decreased the proteolytic activity of Candida albicans at minimum inhibitory concentration. Finally, the EO and its selected active fraction had low cytotoxicity on human cells, with putative mechanisms affecting gene expression in pathways involving chemokines and MAP-kinase (proliferation/apoptosis), as well as adhesion proteins. These findings highlight the potential antifungal activity of the EO from C. sativum leaves and suggest avenues for future translational toxicological research.

  1. G364R mutation of MCM4 detected in human skin cancer cells affects DNA helicase activity of MCM4/6/7 complex.

    PubMed

    Ishimi, Yukio; Irie, Daiki

    2015-06-01

    A number of gene mutations are detected in cells derived from human cancer tissues, but roles of these mutations in cancer cell development are largely unknown. We examined G364R mutation of MCM4 detected in human skin cancer cells. Formation of MCM4/6/7 complex is not affected by the mutation. Consistent with this notion, the binding to MCM6 is comparable between the mutant MCM4 and wild-type MCM4. Nuclear localization of this mutant MCM4 expressed in HeLa cells supports this conclusion. Purified MCM4/6/7 complex containing the G364R MCM4 exhibited similar levels of single-stranded DNA binding and ATPase activities to the complex containing wild-type MCM4. However, the mutant complex showed only 30-50% of DNA helicase activity of the wild-type complex. When G364R MCM4 was expressed in HeLa cells, it was fractionated into nuclease-sensitive chromatin fraction, similar to wild-type MCM4. These results suggest that this mutation does not affect assembly of MCM2-7 complex on replication origins but it interferes some step at function of MCM2-7 helicase. Thus, this mutation may contribute to cancer cell development by disturbing DNA replication.

  2. Inhibition of retinoic acid-induced activation of 3' human HOXB genes by antisense oligonucleotides affects sequential activation of genes located upstream in the four HOX clusters.

    PubMed Central

    Faiella, A; Zappavigna, V; Mavilio, F; Boncinelli, E

    1994-01-01

    Most homeobox genes belonging to the Hox family are sequentially activated in embryonal carcinoma cells upon treatment with retinoic acid. Genes located at the 3' end of each one of the four Hox clusters are activated first, whereas upstream Hox genes are activated progressively later. This activation has been extensively studied for human HOX genes in the NT2/D1 cell line and shown to take place at the transcriptional level. To understand the molecular mechanisms of sequential HOX gene activation in these cells, we tried to modulate the expression of 3' HOX genes through the use of antisense oligonucleotides added to the culture medium. We chose the HOXB locus. A 5- to 15-fold reduction of the expression of HOXB1 and HOXB3 was sufficient to produce a significant inhibition of the activation of the upstream HOXB genes, as well as of their paralogs in the HOXA, HOXC, and HOXD clusters. Conversely, no effect was detectable on downstream HOX genes. The extent of this inhibition increased for progressively more-5' genes. The stability of the corresponding mRNAs appeared to be unaffected, supporting the idea that the observed effect might be mediated at the transcriptional level. These data suggest a cascade model of progressive activation of Hox genes, with a 3'-to-5' polarity. Images PMID:7911240

  3. Parathyroid Hormone Receptor Type 1/Indian Hedgehog Expression Is Preserved in the Growth Plate of Human Fetuses Affected with Fibroblast Growth Factor Receptor Type 3 Activating Mutations

    PubMed Central

    Cormier, Sarah; Delezoide, Anne-Lise; Benoist-Lasselin, Catherine; Legeai-Mallet, Laurence; Bonaventure, Jacky; Silve, Caroline

    2002-01-01

    The fibroblast growth factor receptor type 3 (FGFR3) and Indian hedgehog (IHH)/parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1) systems are both essential regulators of endochondral ossification. Based on mouse models, activation of the FGFR3 system is suggested to regulate the IHH/PTHR1 pathway. To challenge this possible interaction in humans, we analyzed the femoral growth plates from fetuses carrying activating FGFR3 mutations (9 achondroplasia, 21 and 8 thanatophoric dysplasia types 1 and 2, respectively) and 14 age-matched controls by histological techniques and in situ hybridization using riboprobes for human IHH, PTHR1, type 10 and type 1 collagen transcripts. We show that bone-perichondrial ring enlargement and growth plate increased vascularization in FGFR3-mutated fetuses correlate with the phenotypic severity of the disease. PTHR1 and IHH expression in growth plates, bone-perichondrial rings and vascular canals is not affected by FGFR3 mutations, irrespective of the mutant genotype and age, and is in keeping with cell phenotypes. These results indicate that in humans, FGFR3 signaling does not down-regulate the main players of the IHH/PTHR1 pathway. Furthermore, we show that cells within the bone-perichondrial ring in controls and patients express IHH, PTHR1, and type 10 and type 1 collagen transcripts, suggesting that bone-perichondrial ring formation involves cells of both chondrocytic and osteoblastic phenotypes. PMID:12368206

  4. Urban Biodiversity, City-Dwellers and Conservation: How Does an Outdoor Activity Day Affect the Human-Nature Relationship?

    PubMed Central

    Jaillon, Alexandre; Piron, Armony; Julliard, Romain; Raymond, Richard; Simon, Laurent; Prévot-Julliard, Anne-Caroline

    2012-01-01

    Urban conservation education programs aim to increase knowledge and awareness towards biodiversity and to change attitudes and behaviour towards the environment. However, to date, few urban conservation education studies have evaluated to what extent these programs have managed to achieve their goals. In this study, we experimentally explored the influence of an urban conservation activity day on individual knowledge, awareness and actions towards biodiversity, in both the short and longer term. We organised three activity days in Paris (France), during which people were invited to participate in urban conservation efforts. Both quantitative (questionnaire) and qualitative (interviews) methods were employed to investigate the influence of this short urban nature experience on the relationships that city-dwellers develop with nearby biodiversity. We found a strong positive correlation between the levels of participation and an immediate interest towards local urban biodiversity. In the longer term, however, although participants claimed to have gained more knowledge, local awareness and interest for species in their daily environment, they did not seem to extend this interest to participating in other related activities. These results highlight the complexity of validating the effectiveness of this type of education program for achieving conservation goals. Although such a short activity may only have a limited environmental impact, it nevertheless seems to increase people's knowledge, awareness, interest and concern. We therefore believe that when repeated locally, these short conservation education programs could enhance people's experience with nature in cities and achieve conservation goals more fully. PMID:22715403

  5. Urban biodiversity, city-dwellers and conservation: how does an outdoor activity day affect the human-nature relationship?

    PubMed

    Shwartz, Assaf; Cosquer, Alix; Jaillon, Alexandre; Piron, Armony; Julliard, Romain; Raymond, Richard; Simon, Laurent; Prévot-Julliard, Anne-Caroline

    2012-01-01

    Urban conservation education programs aim to increase knowledge and awareness towards biodiversity and to change attitudes and behaviour towards the environment. However, to date, few urban conservation education studies have evaluated to what extent these programs have managed to achieve their goals. In this study, we experimentally explored the influence of an urban conservation activity day on individual knowledge, awareness and actions towards biodiversity, in both the short and longer term.We organised three activity days in Paris (France), during which people were invited to participate in urban conservation efforts. Both quantitative (questionnaire) and qualitative (interviews) methods were employed to investigate the influence of this short urban nature experience on the relationships that city-dwellers develop with nearby biodiversity. We found a strong positive correlation between the levels of participation and an immediate interest towards local urban biodiversity. In the longer term, however, although participants claimed to have gained more knowledge, local awareness and interest for species in their daily environment, they did not seem to extend this interest to participating in other related activities. These results highlight the complexity of validating the effectiveness of this type of education program for achieving conservation goals. Although such a short activity may only have a limited environmental impact, it nevertheless seems to increase people's knowledge, awareness, interest and concern. We therefore believe that when repeated locally, these short conservation education programs could enhance people's experience with nature in cities and achieve conservation goals more fully.

  6. A risk variant for alcoholism in the NMDA receptor affects amygdala activity during fear conditioning in humans.

    PubMed

    Cacciaglia, Raffaele; Nees, Frauke; Pohlack, Sebastian T; Ruttorf, Michaela; Winkelmann, Tobias; Witt, Stephanie H; Nieratschker, Vanessa; Rietschel, Marcella; Flor, Herta

    2013-09-01

    People at high risk for alcoholism show deficits in aversive learning, as indicated by impaired electrodermal responses during fear conditioning, a basic form of associative learning that depends on the amygdala. A positive family history of alcohol dependence has also been related to decreased amygdala responses during emotional processing. In the present study we report reduced amygdala activity during the acquisition of conditioned fear in healthy carriers of a risk variant for alcoholism (rs2072450) in the NR2A subunit-containing N-methyl-d-aspartate (NMDA)-receptor. These results indicate that rs2072450 might confer risk for alcohol dependence through deficient fear acquisition indexed by a diminished amygdala response during aversive learning, and provide a neural basis for a weak behavioral inhibition previously documented in individuals at high risk for alcohol dependence. Carriers of the risk variant additionally exhibit dampened insula activation, a finding that further strengthens our data, given the importance of this brain region in fear conditioning.

  7. Stimulus intensity affects early sensory processing: visual contrast modulates evoked gamma-band activity in human EEG.

    PubMed

    Schadow, Jeanette; Lenz, Daniel; Thaerig, Stefanie; Busch, Niko A; Fründ, Ingo; Rieger, Jochem W; Herrmann, Christoph S

    2007-10-01

    We studied the effect of different contrast levels on the visual evoked gamma-band response (GBR) in order to investigate whether the GBR is modulated in a similar manner as previously reported for visual evoked potentials. Previous studies showed that the GBR can be modulated by individual characteristics (age) and experimental conditions (task difficulty, attention). However, stimulus properties, such as size and spatial frequency, also have a large impact on the GBR, which necessitates identification and control of relevant stimulus properties for optimal experimental setups. Twenty-one healthy participants were investigated during a forced-choice discrimination task. Sinusoidal gratings were presented at three contrast levels with a constant spatial frequency of 5 cycles per degree visual arc (cpd). The present data replicate the results reported for visual evoked potentials and exhibit a contrast dependent modulation of the GBR. Gamma activity is increased for higher contrast levels. These results demonstrate the importance of stimulus contrast for evoked gamma activity. Thus, it appears meaningful to control the contrast of stimuli in experiments investigating the role of gamma activity in perception and information processing.

  8. Do recreational activities affect coastal biodiversity?

    NASA Astrophysics Data System (ADS)

    Riera, Rodrigo; Menci, Cristiano; Sanabria-Fernández, José Antonio; Becerro, Mikel A.

    2016-09-01

    Human activities are largely affecting coastal communities worldwide. Recreational perturbations have been overlooked in comparison to other perturbations, yet they are potential threats to marine biodiversity. They affect coastal communities in different ways, underpinning consistent shifts in fish and invertebrates assemblages. Several sites were sampled subjected to varying effects by recreational fishermen (low and high pressure) and scuba divers (low and high) in an overpopulated Atlantic island. Non-consistent differences in ecological, trophic and functional diversity were found in coastal communities, considering both factors ("diving" and "fishing"). Multivariate analyses only showed significant differences in benthic invertebrates between intensively-dived and non-dived sites. The lack of clear trends may be explained by the depletion of coastal resources in the study area, an extensively-affected island by overfishing.

  9. Affect in Human-Robot Interaction

    DTIC Science & Technology

    2014-01-01

    even without deliberately modeling them: for example, if a robot backs away from a staircase it might be interpreted as a fear of falling by a person...chosen to deliberately embed explicit models of affect into robots, with the express purpose of enhancing the relationship between the human and robot...many psychological models of human affect have been explored. Two examples that have had commercial success are described

  10. How do humans affect wildlife nematodes?

    USGS Publications Warehouse

    Weinstein, Sara B.; Lafferty, Kevin D.

    2015-01-01

    Human actions can affect wildlife and their nematode parasites. Species introductions and human-facilitated range expansions can create new host–parasite interactions. Novel hosts can introduce parasites and have the potential to both amplify and dilute nematode transmission. Furthermore, humans can alter existing nematode dynamics by changing host densities and the abiotic conditions that affect larval parasite survival. Human impacts on wildlife might impair parasites by reducing the abundance of their hosts; however, domestic animal production and complex life cycles can maintain transmission even when wildlife becomes rare. Although wildlife nematodes have many possible responses to human actions, understanding host and parasite natural history, and the mechanisms behind the changing disease dynamics might improve disease control in the few cases where nematode parasitism impacts wildlife.

  11. How do humans affect wildlife nematodes?

    PubMed

    Weinstein, Sara B; Lafferty, Kevin D

    2015-05-01

    Human actions can affect wildlife and their nematode parasites. Species introductions and human-facilitated range expansions can create new host-parasite interactions. Novel hosts can introduce parasites and have the potential to both amplify and dilute nematode transmission. Furthermore, humans can alter existing nematode dynamics by changing host densities and the abiotic conditions that affect larval parasite survival. Human impacts on wildlife might impair parasites by reducing the abundance of their hosts; however, domestic animal production and complex life cycles can maintain transmission even when wildlife becomes rare. Although wildlife nematodes have many possible responses to human actions, understanding host and parasite natural history, and the mechanisms behind the changing disease dynamics might improve disease control in the few cases where nematode parasitism impacts wildlife.

  12. Homo- and hetero-dimerization of human UDP-glucuronosyltransferase 2B7 (UGT2B7) wild type and its allelic variants affect zidovudine glucuronidation activity.

    PubMed

    Yuan, Lingmin; Qian, Sainan; Xiao, Yongsheng; Sun, Hongying; Zeng, Su

    2015-05-01

    Most human UDP-glucuronosyltransferase (UGT; EC 2.4.1.17) genes contain non-synonymous single nucleotide polymorphisms (nsSNPs) which cause amino acid substitutions. Allelic variants caused by nsSNPs may exhibit absent or reduced enzyme activity. UGT2B7 is one of the most important UGTs that glucuronidates abundant endobiotics and xenobiotics, such as estriol, morphine, and anticancer drugs. Three nsSNPs, UGT2B7*71S (211G>T), UGT2B7*2 (802C>T) and UGT2B7*5 (1192G>A) are observed in the UGT2B7 gene, and they code for allozymes UGT2B7*71S (A71S), UGT2B7*2 (H268Y), and UGT2B7*5 (D398N). UGT2B7 has been observed to form oligomers that affect its enzymatic activity and in this study, we investigated protein-protein interactions among UGT2B7 allozymes wild type (WT), A71S, H268Y and D398N, by performing a systematic quantitative fluorescence resonance energy transfer (FRET) analysis in combination with co-immunoprecipitation assay. Quantitative FRET analysis revealed that UGT2B7 allozymes formed homo- and hetero-dimers and showed distinct features in donor-acceptor distances. Both codon 71 and codon 268 in the N-terminal domain were involved in the dimeric interaction. Co-immunoprecipitation experiments also proved that UGT2B7 allozymes formed stable dimers. The glucuronidation activities of homo- and hetero-dimers were further tested with zidovudine as the substrate. An increase in activity was observed when WT hetero-dimerized with A71S compared with homo-dimers, while both H268Y and D398N impaired the activity of WT and A71S by forming hetero-dimers. In addition, zidovudine glucuronidation activity is associated with FRET distance. These findings provide insights into the consequences of amino acid substitution in UGT2B7 on zidovudine glucuronidation and the association between protein-protein interaction and glucuronidation activity.

  13. Activation of Human Complement System by Dextran-Coated Iron Oxide Nanoparticles Is Not Affected by Dextran/Fe Ratio, Hydroxyl Modifications, and Crosslinking

    PubMed Central

    Wang, Guankui; Chen, Fangfang; Banda, Nirmal K.; Holers, V. Michael; Wu, LinPing; Moghimi, S. Moein; Simberg, Dmitri

    2016-01-01

    While having tremendous potential as therapeutic and imaging tools, the clinical use of engineered nanoparticles has been associated with serious safety concerns. Activation of the complement cascade and the release of proinflammatory factors C3a and C5a may contribute to infusion-related reactions, whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry in inciting complement in human serum. Using complement inhibitors and measuring levels of fluid phase markers (sC5b-9, C5a, and Bb), we found that the majority of human complement activation by SPIO is through the alternative pathways (AP). SPIO prepared with high dextran/iron ratio showed some complement activation via calcium-sensitive pathways, but the AP was responsible for the bulk of complement activation and amplification. Activation via the AP required properdin, the positive regulator of the alternative C3bBb convertase. Modification of sugar alcohols of dextran with alkylating, acylating, or crosslinking agents did not overcome complement activation and C3 opsonization. These data demonstrate that human complement activation is independent of dextran modification of SPIO and suggest a crucial role of the AP in immune recognition of nano-assemblies in human serum. PMID:27777575

  14. Humans process dog and human facial affect in similar ways.

    PubMed

    Schirmer, Annett; Seow, Cui Shan; Penney, Trevor B

    2013-01-01

    Humans share aspects of their facial affect with other species such as dogs. Here we asked whether untrained human observers with and without dog experience are sensitive to these aspects and recognize dog affect with better-than-chance accuracy. Additionally, we explored similarities in the way observers process dog and human expressions. The stimulus material comprised naturalistic facial expressions of pet dogs and human infants obtained through positive (i.e., play) and negative (i.e., social isolation) provocation. Affect recognition was assessed explicitly in a rating task using full face images and images cropped to reveal the eye region only. Additionally, affect recognition was assessed implicitly in a lexical decision task using full faces as primes and emotional words and pseudowords as targets. We found that untrained human observers rated full face dog expressions from the positive and negative condition more accurately than would be expected by chance. Although dog experience was unnecessary for this effect, it significantly facilitated performance. Additionally, we observed a range of similarities between human and dog face processing. First, the facial expressions of both species facilitated lexical decisions to affectively congruous target words suggesting that their processing was equally automatic. Second, both dog and human negative expressions were recognized from both full and cropped faces. Third, female observers were more sensitive to affective information than were male observers and this difference was comparable for dog and human expressions. Together, these results extend existing work on cross-species similarities in facial emotions and provide evidence that these similarities are naturally exploited when humans interact with dogs.

  15. Humans Process Dog and Human Facial Affect in Similar Ways

    PubMed Central

    Schirmer, Annett; Seow, Cui Shan; Penney, Trevor B.

    2013-01-01

    Humans share aspects of their facial affect with other species such as dogs. Here we asked whether untrained human observers with and without dog experience are sensitive to these aspects and recognize dog affect with better-than-chance accuracy. Additionally, we explored similarities in the way observers process dog and human expressions. The stimulus material comprised naturalistic facial expressions of pet dogs and human infants obtained through positive (i.e., play) and negative (i.e., social isolation) provocation. Affect recognition was assessed explicitly in a rating task using full face images and images cropped to reveal the eye region only. Additionally, affect recognition was assessed implicitly in a lexical decision task using full faces as primes and emotional words and pseudowords as targets. We found that untrained human observers rated full face dog expressions from the positive and negative condition more accurately than would be expected by chance. Although dog experience was unnecessary for this effect, it significantly facilitated performance. Additionally, we observed a range of similarities between human and dog face processing. First, the facial expressions of both species facilitated lexical decisions to affectively congruous target words suggesting that their processing was equally automatic. Second, both dog and human negative expressions were recognized from both full and cropped faces. Third, female observers were more sensitive to affective information than were male observers and this difference was comparable for dog and human expressions. Together, these results extend existing work on cross-species similarities in facial emotions and provide evidence that these similarities are naturally exploited when humans interact with dogs. PMID:24023954

  16. Biogeochemistry of a tropical river affected by human activities in its catchment: Brantas River estuary and coastal waters of Madura Strait, Java, Indonesia

    NASA Astrophysics Data System (ADS)

    Jennerjahn, T. C.; Ittekkot, V.; Klöpper, S.; Adi, Seno; Purwo Nugroho, Sutopo; Sudiana, Nana; Yusmal, Anyuta; Prihartanto; Gaye-Haake, B.

    2004-07-01

    On a global scale tropical SE Asia is critical in terms of fluvial nutrient and sediment input into the ocean as well as in terms of human modifications of the coastal zone altering these inputs. In order to obtain information on the biogeochemistry of the Brantas River estuary and adjacent coastal waters of the Madura Strait in eastern Java, Indonesia, a densely-populated area which is strongly affected by human activities in the river catchment, we investigated water, suspended matter and sediments from estuarine and coastal waters and plants and soils from the catchment collected during the dry season. Water samples were analyzed for dissolved nutrients and phytoplankton abundance and composition. Suspended matter, sediment, plant and soil samples were analyzed for carbon, nitrogen, amino acids and stable carbon and nitrogen isotopes. Nutrient concentrations were high in the river and then decreased rapidly seaward. Runoff from agricultural soils may be a major nutrient source. Phytoplankton was dominated by diatoms and most abundant in the estuarine mixing zone. A fairly high phytoplankton abundance despite nitrate-depletion and an N/P ratio <4 in coastal waters indicates additional nitrogen sources. Biogeochemical characteristics and stable isotopes indicate the autochthonous origin of suspended organic matter (OM) during the dry season. Major part of the fluvial input appears to be trapped in the inner estuary. Similar information obtained from the analysis of sediments suggests seasonal differences in the quantity and origin of suspended sediments and OM transported by the river with high inputs into coastal waters during the rainy season, the period of peak river discharge. The amino acid composition in combination with stable isotopes indicates agricultural soils to be a major OM source during that time. A high proportion of amino acid-bound nitrogen in suspended matter and sediments and the presumed sources of dissolved nitrogen other than nitrate to

  17. Zoonotic helminths affecting the human eye

    PubMed Central

    2011-01-01

    Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths that affect human eyes (HIE) may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis), food consumption (sparganosis, trichinellosis) and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis). Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs) or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt Seneca Ep 6,5 Men believe their eyes more than their ears PMID:21429191

  18. Human freezing in response to affective films.

    PubMed

    Hagenaars, Muriel A; Roelofs, Karin; Stins, John F

    2014-01-01

    Human freezing has been objectively assessed using a passive picture viewing paradigm as an analog for threat. These results should be replicated for other stimuli in order to determine their stability and generalizability. Affective films are used frequently to elicit affective responses, but it is unknown whether they also elicit freezing-like defense responses. To test whether this is the case, 50 participants watched neutral, pleasant and unpleasant film fragments while standing on a stabilometric platform and wearing a polar band to assess heart rate. Freezing-like responses (indicated by overall reduced body sway and heart rate deceleration) were observed for the unpleasant film only. The unpleasant film also elicited early reduced body sway (1-2 s after stimulus onset). Heart rate and body sway were correlated during the unpleasant film only. The results suggest that ecologically valid stimuli like films are adequate stimuli in evoking defense responses. The results also underscore the importance of including time courses in human experimental research on defense reactions in order to delineate different stages in the defense response.

  19. Deletion of N-terminal amino acids from human lecithin:cholesterol acyltransferase differentially affects enzyme activity toward alpha- and beta-substrate lipoproteins.

    PubMed

    Vickaryous, Nicola K; Teh, Evelyn M; Stewart, Bruce; Dolphin, Peter J; Too, Catherine K L; McLeod, Roger S

    2003-03-21

    Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for generation of the majority of the cholesteryl esters (CE) in human plasma. Although most plasma cholesterol esterification occurs on high-density lipoprotein (HDL), via alpha-LCAT activity, esterification also occurs on low-density lipoprotein (LDL) via the beta-activity of the enzyme. Computer threading techniques have provided a three-dimensional model for use in the structure-function analysis of the core and catalytic site of the LCAT protein, but the model does not extend to the N-terminal region of the enzyme, which may mediate LCAT interaction with lipoprotein substrates. In the present study, we have examined the functional consequences of deletion of the highly conserved hydrophobic N-terminal amino acids (residues 1-5) of human LCAT. Western blot analysis showed that the mutant proteins (Delta 1-Delta 5) were synthesized and secreted from transfected COS-7 cells at levels approximately equivalent to those of wild-type hLCAT. The secreted proteins had apparent molecular weights of 67 kDa, indicating that they were correctly processed and glycosylated during cellular transit. However, deletion of the first residue of the mature LCAT protein (Delta 1 mutant) resulted in a dramatic loss of alpha-LCAT activity (5% of wild type using reconstituted HDL substrate, rHDL), although this mutant retained full beta-LCAT activity (108% of wild-type using human LDL substrate). Removal of residues 1 and 2 (Delta 2 mutant) abolished alpha-LCAT activity and reduced beta-LCAT activity to 12% of wild type. Nevertheless, LCAT Delta 1 and Delta 2 mutants retained their ability to bind to rHDL and LDL lipoprotein substrates. The dramatic loss of enzyme activity suggests that the N-terminal residues of LCAT may be involved in maintaining the conformation of the lid domain and influence activation by the alpha-LCAT cofactor apoA-I (in Delta 1) and/or loss of enzyme activity (in Delta 1-Delta 5). Since the

  20. How does the anthropogenic activity affect the spring discharge?

    NASA Astrophysics Data System (ADS)

    Hao, Yonghong; Zhang, Juan; Wang, Jiaojiao; Li, Ruifang; Hao, Pengmei; Zhan, Hongbin

    2016-09-01

    Karst hydrological process has largely been altered by climate change and human activity. In many places throughout the world, human activity (e.g. groundwater pumping and dewatering from mining) has intensified and surpassed climate change, where human activity becomes the primary factor that affects groundwater system. But it is still largely unclear how the human activity affects spring discharge in magnitude and periodicity. This study investigates the effects of anthropogenic activity on spring discharge, using the Xin'an Springs of China as an example. The Xin'an Spring discharge were divided into two time periods: the pre-development period from 1956 to 1971 and the post-development period from 1972 to 2013. We confirm the dividing time (i.e. 1971) of these two periods using the Wilcoxon rank-sum test. Then the wavelet transform and wavelet coherence were used to analyze the karst hydrological processes for the two periods respectively. We analyze the correlations of precipitation and the Xin'an spring discharge with the monsoons including the Indian Summer Monsoon (ISM) and the West North Pacific Monsoon (WNPM) and the climate teleconnections including El Niño Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO), respectively. The results indicated that the spring discharge was attenuated about 19.63% under the influence of human activity in the Xin'an Springs basin. However, human activity did not alter the size of the resonance frequencies between the spring discharge and the monsoons. In contrast, it reinforced the periodicities of the monsoons-driven spring discharge. It suggested that human has adapted to the major climate periodicities, and human activity had the same rhyme with the primary climate periodicity. In return, human activity enhances the correlation between the monsoons and the spring discharge.

  1. On the Use of Hydrological Models and Satellite Data to Study the Water Budget of River Basins Affected by Human Activities: Examples from the Garonne Basin of France

    NASA Astrophysics Data System (ADS)

    Martin, Eric; Gascoin, Simon; Grusson, Youen; Murgue, Clément; Bardeau, Mélanie; Anctil, François; Ferrant, Sylvain; Lardy, Romain; Le Moigne, Patrick; Leenhardt, Delphine; Rivalland, Vincent; Sánchez Pérez, José-Miguel; Sauvage, Sabine; Therond, Olivier

    2016-03-01

    Natural and anthropogenic forcing factors and their changes significantly impact water resources in many river basins around the world. Information on such changes can be derived from fine scale in situ and satellite observations, used in combination with hydrological models. The latter need to account for hydrological changes caused by human activities to correctly estimate the actual water resource. In this study, we consider the catchment area of the Garonne river (in France) to investigate the capabilities of space-based observations and up-to-date hydrological modeling in estimating water resources of a river basin modified by human activities and a changing climate. Using the ISBA-MODCOU and SWAT hydrological models, we find that the water resources of the Garonne basin display a negative climate trend since 1960. The snow component of the two models is validated using the moderate-resolution imaging spectroradiometer snow cover extent climatology. Crop sowing dates based on remote sensing studies are also considered in the validation procedure. Use of this dataset improves the simulated evapotranspiration and river discharge amounts when compared to conventional data. Finally, we investigate the benefit of using the MAELIA multi-agent model that accounts for a realistic agricultural and management scenario. Among other results, we find that changes in crop systems have significant impacts on water uptake for agriculture. This work constitutes a basis for the construction of a future modeling framework of the sociological and hydrological system of the Garonne river region.

  2. 28 CFR 55.15 - Affected activities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.15 Affected... of applicable language minority groups to be effectively informed of and participate effectively in voting-connected activities. Accordingly, the quoted language should be broadly construed to apply to...

  3. 28 CFR 55.15 - Affected activities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.15 Affected... of applicable language minority groups to be effectively informed of and participate effectively in voting-connected activities. Accordingly, the quoted language should be broadly construed to apply to...

  4. 28 CFR 55.15 - Affected activities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.15 Affected... of applicable language minority groups to be effectively informed of and participate effectively in voting-connected activities. Accordingly, the quoted language should be broadly construed to apply to...

  5. 28 CFR 55.15 - Affected activities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.15 Affected... of applicable language minority groups to be effectively informed of and participate effectively in voting-connected activities. Accordingly, the quoted language should be broadly construed to apply to...

  6. 28 CFR 55.15 - Affected activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Minority Language Materials and Assistance § 55.15 Affected... of applicable language minority groups to be effectively informed of and participate effectively in voting-connected activities. Accordingly, the quoted language should be broadly construed to apply to...

  7. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  8. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  9. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  10. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  11. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  12. Vaccine-Mediated Activation of Human TLR4 Is Affected by Modulation of Culture Conditions during Whole-Cell Pertussis Vaccine Preparation

    PubMed Central

    Hoonakker, Marieke E.; Verhagen, Lisa M.; Pupo, Elder; de Haan, Alex; Metz, Bernard; Hendriksen, Coenraad F. M.; Han, Wanda G. H.; Sloots, Arjen

    2016-01-01

    The potency of whole-cell pertussis (wP) vaccines is still determined by an intracerebral mouse protection test. To allow development of suitable in vitro alternatives to this test, insight into relevant parameters to monitor the consistency of vaccine quality is essential. To this end, a panel of experimental wP vaccines of varying quality was prepared by sulfate-mediated suppression of the BvgASR master virulence regulatory system of Bordetella pertussis during cultivation. This system regulates the transcription of a range of virulence proteins, many of which are considered important for the induction of effective host immunity. The protein compositions and in vivo potencies of the vaccines were BvgASR dependent, with the vaccine containing the highest amount of virulence proteins having the highest in vivo potency. Here, the capacities of these vaccines to stimulate human Toll-like receptors (hTLR) 2 and 4 and the role these receptors play in wP vaccine-mediated activation of antigen-presenting cells in vitro were studied. Prolonged BvgASR suppression was associated with a decreased capacity of vaccines to activate hTLR4. In contrast, no significant differences in hTLR2 activation were observed. Similarly, vaccine-induced activation of MonoMac-6 and monocyte-derived dendritic cells was strongest with the highest potency vaccine. Blocking of TLR2 and TLR4 showed that differences in antigen-presenting cell activation could be largely attributed to vaccine-dependent variation in hTLR4 signalling. Interestingly, this BvgASR-dependent decrease in hTLR4 activation coincided with a reduction in GlcN-modified lipopolysaccharides in these vaccines. Accordingly, expression of the lgmA-C genes, required for this glucosamine modification, was significantly reduced in bacteria exposed to sulfate. Together, these findings demonstrate that the BvgASR status of bacteria during wP vaccine preparation is critical for their hTLR4 activation capacity and suggest that including

  13. Dust in the western U.S.: how biological, physical and human activities at the local scale interact to affect hydrologic function at the landscape scale (Invited)

    NASA Astrophysics Data System (ADS)

    Belnap, J.; Reheis, M. C.; Munson, S. M.

    2009-12-01

    Dryland regions constitute over 35% of terrestrial lands around the globe. Limited rainfall in these regions restricts plant growth and the spaces between vascular plants are often large. Most interspace soils are protected from wind erosion by the cover of rocks, physical crusts, and biological crusts (cyanobacteria, lichens, and mosses). However, disturbance of the soil surface in dryland regions (e.g., recreation, livestock, mining and energy exploration, military exercises, fire) reduces or eliminates the protective cover of the soils. Rising temperatures will reduce soil moisture and thus plant cover. Wind tunnel data show that most desert surfaces produce little sediment under typical wind speeds. However, disturbing the soil surface with vehicles, humans, or animals resulted in much higher sediment production from all surfaces tested, regardless of parent material, texture, or age of the soil surface. Synergist effects, such as surface disturbance occurring during drought periods in annualized plant communities, can create very large dust events. As surface disturbance, invasion, and drought are expected to increase in the future, an increase in dust production can be expected as well. Increased particulates in the air threaten human well-being through disease, highway accidents, and economic losses. Where dust losses are greater than the inputs, the source areas lose carbon and nutrients. These compounds are transferred to high elevation regions, where such fertilization likely impacts ecosystem function. Deposition of dust on the snowpack darkens the surface, increasing snowmelt by 30 days or more and exposing soils to evaporation, all of which decrease the quantity and quality of water in major streams and rivers. As increases occur in temperature, pumping of shallow aquifers, human activities, and invasion of exotic annual plants in dryland regions, the frequency, severity, and negative impact of dust storms is expected to increase as well. The

  14. Human Development Program: Level V Activity Guide.

    ERIC Educational Resources Information Center

    Ball, Geraldine

    The curriculum guide presents the activities component of the Human Development Program for grade 5. The Human Development Program (HDP) is an affective curricular approach developed by psychologists to help teachers instill responsibility and self-confidence in children. The activity guide presents topics and directions for 180 sequential Human…

  15. Human Infrastructure & Human Activity Detection

    DTIC Science & Technology

    2007-07-01

    researchers are developing sensors systems that detect footfalls (or gait ) [1, 2], speech, the spectral response of human skin, etc [3]. Little work has...cone shaped field of view. • Visible imagers can capture color or grayscale video for human gait detection and object recognition. • Infrared...his/her gait produces a unique signature [13]. Indirect means of detecting personnel include the usage of acoustic, seismic, magnetic, passive

  16. [Affective computing--a mysterious tool to explore human emotions].

    PubMed

    Li, Xin; Li, Honghong; Dou, Yi; Hou, Yongjie; Li, Changwu

    2013-12-01

    Perception, affection and consciousness are basic psychological functions of human being. Affection is the subjective reflection of different kinds of objects. The foundation of human being's thinking is constituted by the three basic functions. Affective computing is an effective tool of revealing the affectiveness of human being in order to understand the world. Our research of affective computing focused on the relation, the generation and the influent factors among different affections. In this paper, the affective mechanism, the basic theory of affective computing, is studied, the method of acquiring and recognition of affective information is discussed, and the application of affective computing is summarized as well, in order to attract more researchers into this working area.

  17. Solar activity affects avian timing of reproduction

    PubMed Central

    Visser, Marcel E.; Sanz, Juan José

    2009-01-01

    Avian timing of reproduction is strongly affected by ambient temperature. Here we show that there is an additional effect of sunspots on laying date, from five long-term population studies of great and blue tits (Parus major and Cyanistes caeruleus), demonstrating for the first time that solar activity not only has an effect on population numbers but that it also affects the timing of animal behaviour. This effect is statistically independent of ambient temperature. In years with few sunspots, birds initiate laying late while they are often early in years with many sunspots. The sunspot effect may be owing to a crucial difference between the method of temperature measurements by meteorological stations (in the shade) and the temperatures experienced by the birds. A better understanding of the impact of all the thermal components of weather on the phenology of ecosystems is essential when predicting their responses to climate change. PMID:19574283

  18. Intrinsic Patterns of Human Activity

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  19. Infrasound from Wind Turbines Could Affect Humans

    ERIC Educational Resources Information Center

    Salt, Alec N.; Kaltenbach, James A.

    2011-01-01

    Wind turbines generate low-frequency sounds that affect the ear. The ear is superficially similar to a microphone, converting mechanical sound waves into electrical signals, but does this by complex physiologic processes. Serious misconceptions about low-frequency sound and the ear have resulted from a failure to consider in detail how the ear…

  20. Does Globalization Affect Human Well-Being?

    ERIC Educational Resources Information Center

    Tsai, Ming-Chang

    2007-01-01

    The prevailing theorizing of globalization's influence of human well-being suggests to assess both the favorable and unfavorable outcomes. This study formulates a dialectical model, adopts a comprehensive globalization measure and uses a three-wave panel data during 1980-2000 to empirically test direct and indirect effects of global flows' human…

  1. Ectoparasites from feral pigeons affecting humans.

    PubMed

    Haag-Wackernagel, Daniel; Bircher, Andreas J

    2010-01-01

    Feral pigeons pose a considerable health risk to the human population. They are vectors of infectious diseases and source of antigens causing allergic diseases. Breeding and roosting sites of pigeons harbor parasites that may infest humans. In the present article, a concomitant parasitization of a young female with 3 different ectoparasites, the bedbug Cimex lectularius, the pigeon tick Argas reflexus and the red mite Dermanyssus gallinae, is reported. The parasites invaded the apartment from a balcony used as roost by feral pigeons and infested the patient continuously over a period of more than 2 months. To our knowledge this case presents the first record of a coincidental infestation of a single patient with several ectoparasite species deriving from feral pigeons. Additionally we report general symptoms in the patient probably caused by the high number of stings. Dermatologists should be aware of the possibility of an infestation with ectoparasites deriving from feral pigeons. In a review we give an overview on the most important ectoparasites transmitted from feral pigeons to humans and their importance for the dermatologist.

  2. TGF-β Affects the Differentiation of Human GM-CSF+ CD4+ T Cells in an Activation- and Sodium-Dependent Manner

    PubMed Central

    Éliás, Szabolcs; Schmidt, Angelika; Kannan, Venkateshan; Andersson, John; Tegnér, Jesper

    2016-01-01

    The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is involved in the pathogenesis of chronic inflammatory diseases such as multiple sclerosis. However, the environmental cues promoting differentiation of GM-CSF producing T cells are unclear. Herein, we performed a broad experimental screening of cytokines and data-driven analysis assessing their ability to induce human GM-CSF+ CD4+ T cells and their subpopulations. TGF-β was discovered to induce GM-CSF production independently of proliferation and IL-2 signaling including STAT5. In contrast, IL-6 and IL-23 decreased GM-CSF production. On the population level, GM-CSF induction was highly correlated with expression of FOXP3 across cytokine stimulations but not with that of IL-17. However, on single-cell level GM-CSF and IFN-γ expression were most correlated, independently of the cytokine environment. Importantly, under low sodium conditions in the medium or upon stimulation with plate-bound instead of bead-bound anti-CD3 and anti-CD28 antibodies, the effects of TGF-β on GM-CSF, but not on FOXP3, were reversed. Our analysis indicates a novel role for TGF-β in generating GM-CSF+ subsets of human CD4+ T cells. These results are important for understanding of autoimmune disease and therapeutic considerations. PMID:28066414

  3. Concentration of fibrin and presence of plasminogen affect proliferation, fibrinolytic activity, and morphology of human fibroblasts and keratinocytes in 3D fibrin constructs.

    PubMed

    Reinertsen, Erik; Skinner, Michael; Wu, Benjamin; Tawil, Bill

    2014-11-01

    Fibrin is a hemostatic protein found in the clotting cascade. It is used in the operating room to stop bleeding and deliver cells and growth factors to heal wounds. However, formulations of clinically approved fibrin are optimized for hemostasis, and the extent to which biochemical and physical cues in fibrin mediate skin cell behavior is not fully understood nor utilized in the design of biomaterials. To determine if the concentration of fibrinogen and the presence of plasminogen affect cell behavior relevant to wound healing, we fabricated three-dimensional fibrin constructs made from 5, 10, or 20 mg/mL of clinical fibrin or plasminogen-depleted (PD) fibrin. We cultured dermal fibroblasts or epidermal keratinocytes in these constructs. Fibroblasts proliferated similarly in both types of fibrin, but keratinocytes proliferated more in low concentrations of clinical fibrin and less in PD fibrin. Clinical fibrin constructs with fibroblasts were less stiff and degraded faster than PD fibrin constructs with fibroblasts. Similarly, keratinocytes degraded clinical fibrin, but not PD fibrin. Fibroblast spreading varied with fibrin concentration in both types of fibrin. In conclusion, the concentration of fibrinogen and the presence of plasminogen affect fibroblast and keratinocyte proliferation, morphology, and fibrin degradation. Creating materials with heterogeneous regions of fibrin formulations and concentrations could be a novel strategy for controlling the phenotype of encapsulated fibroblasts and keratinocytes, and the subsequent biomechanical properties of the construct. However, other well-investigated aspects of wound healing remain to be utilized in the design of fibrin biomaterials, such as autocrine and paracrine signaling between fibroblasts, keratinocytes, and immune cells.

  4. L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance.

    PubMed

    Kelly, Simon P; Gomez-Ramirez, Manuel; Montesi, Jennifer L; Foxe, John J

    2008-08-01

    Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8-14 Hz) activity. We found an increase in hit rate and target discriminability (d') for the combined treatment relative to placebo, and an increase in d' but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.

  5. Functional neuroimaging of human vocalizations and affective speech.

    PubMed

    Frühholz, Sascha; Sander, David; Grandjean, Didier

    2014-12-01

    Neuroimaging studies have verified the important integrative role of the basal ganglia during affective vocalizations. They, however, also point to additional regions supporting vocal monitoring, auditory-motor feedback processing, and online adjustments of vocal motor responses. For the case of affective vocalizations, we suggest partly extending the model to fully consider the link between primate-general and human-specific neural components.

  6. Toward an Affective Pedagogy of Human Rights Education

    ERIC Educational Resources Information Center

    Hung, Ruyu

    2014-01-01

    This paper explores the notion of Affective Pedagogy of Human Rights Education (APHRE) on a theoretical level and suggests a concept of curricular framework. APHRE highlights the significance of affectivity and body in the process of learning, factors usually neglected in the mainstream intellectualistic approach to learning, especially in areas…

  7. Do toxic heavy metals affect antioxidant defense mechanisms in humans?

    PubMed

    Wieloch, Monika; Kamiński, Piotr; Ossowska, Anna; Koim-Puchowska, Beata; Stuczyński, Tomasz; Kuligowska-Prusińska, Magdalena; Dymek, Grażyna; Mańkowska, Aneta; Odrowąż-Sypniewska, Grażyna

    2012-04-01

    The aim of this study was to prove whether anthropogenic pollution affects antioxidant defense mechanisms such as superoxide dismutase (SOD) and catalase (CAT) activity, ferritin (FRT) concentration and total antioxidant status (TAS) in human serum. The study area involves polluted and salted environment (Kujawy region; northern-middle Poland) and Tuchola Forestry (unpolluted control area). We investigated 79 blood samples of volunteers from polluted area and 82 from the control in 2008 and 2009. Lead, cadmium and iron concentrations were measured in whole blood by the ICP-MS method. SOD and CAT activities were measured in serum using SOD and CAT Assay Kits by the standardized colorimetric method. Serum TAS was measured spectrophotometrically by the modified Benzie and Strain (1996) method and FRT concentration-by the immunonefelometric method. Pb and Cd levels and SOD activity were higher in volunteers from polluted area as compared with those from the control (0.0236 mg l(-1) vs. 0.014 mg l(-1); 0.0008 mg l(-1) vs. 0.0005 mg l(-1); 0.137 Um l(-1) vs. 0.055 Um l(-1), respectively). Fe level, CAT activity and TAS were lower in serum of volunteers from polluted area (0.442 g l(-1) vs. 0.476 gl(-1); 3.336 nmol min(-1)ml(-1) vs. 6.017 nmol min(-1)ml(-1); 0.731 Trolox-equivalents vs. 0.936 Trolox-equivalents, respectively), whilst differences in FRT concentration were not significant (66.109 μg l(-1) vs. 37.667 μg l(-1), p=0.3972). Positive correlations between Pb (r=0.206), Cd (r=0.602) and SOD in the inhabitants of polluted area, and between Cd and SOD in the control (r=0.639) were shown. In volunteers from both studied environments TAS-FRT (polluted: r=0.625 vs. control: r=0.837) and Fe-FRT (polluted area: r=0.831 vs. control: r=0.407) correlations, and Pb-FRT (r=0.360) and Pb-TAS (r=0.283) in the control were stated. The higher lead and cadmium concentrations in blood cause an increase of SOD activity. It suggests that this is one of the defense mechanisms of an

  8. Consensus and stratification in the affective meaning of human sociality

    PubMed Central

    Ambrasat, Jens; von Scheve, Christian; Conrad, Markus; Schauenburg, Gesche; Schröder, Tobias

    2014-01-01

    We investigate intrasocietal consensus and variation in affective meanings of concepts related to authority and community, two elementary forms of human sociality. Survey participants (n = 2,849) from different socioeconomic status (SES) groups in German society provided ratings of 909 social concepts along three basic dimensions of affective meaning. Results show widespread consensus on these meanings within society and demonstrate that a meaningful structure of socially shared knowledge emerges from organizing concepts according to their affective similarity. The consensus finding is further qualified by evidence for subtle systematic variation along SES differences. In relation to affectively neutral words, high-status individuals evaluate intimacy-related and socially desirable concepts as less positive and powerful than middle- or low-status individuals, while perceiving antisocial concepts as relatively more threatening. This systematic variation across SES groups suggests that the affective meaning of sociality is to some degree a function of social stratification. PMID:24843121

  9. Consensus and stratification in the affective meaning of human sociality.

    PubMed

    Ambrasat, Jens; von Scheve, Christian; Conrad, Markus; Schauenburg, Gesche; Schröder, Tobias

    2014-06-03

    We investigate intrasocietal consensus and variation in affective meanings of concepts related to authority and community, two elementary forms of human sociality. Survey participants (n = 2,849) from different socioeconomic status (SES) groups in German society provided ratings of 909 social concepts along three basic dimensions of affective meaning. Results show widespread consensus on these meanings within society and demonstrate that a meaningful structure of socially shared knowledge emerges from organizing concepts according to their affective similarity. The consensus finding is further qualified by evidence for subtle systematic variation along SES differences. In relation to affectively neutral words, high-status individuals evaluate intimacy-related and socially desirable concepts as less positive and powerful than middle- or low-status individuals, while perceiving antisocial concepts as relatively more threatening. This systematic variation across SES groups suggests that the affective meaning of sociality is to some degree a function of social stratification.

  10. Mutations affecting enzymatic activity in liver arginase

    SciTech Connect

    Vockley, J.G.; Tabor, D.E.; Goodman, B.K.

    1994-09-01

    The hydrolysis of arginine to ornithine and urea is catalyzed by arginase in the last step of the urea cycle. We examined a group of arginase deficient patients by PCR-SSCP analysis to characterize the molecular basis of this disorder. A heterogeneous population of nonsense mutations, microdeletions, and missense mutations has been identified in our cohort. Microdeletions which introduce premature stop codons downstream of the deletion and nonsense mutations result in no arginase activity. These mutations occur randomly along the gene. The majority of missense mutations identified appear to occur in regions of high cross-species homology. To test the effect of these missense mutations on arginase activity, site-directed mutagenesis was used to re-create the patient mutations for in vivo expression studies in a prokaryotic fusion-protein expression system. Of 4 different missense mutations identified in 6 individuals, only one was located outside of a conserved region. The three substitution mutations within the conserved regions had a significant effect on enzymatic activity (0-3.1 nmole/30min, normal is 1300-1400 nmoles/30min, as determined by in vitro arginase assay), while the fourth mutation, a T to S substitution, did not. In addition, site-directed mutagenesis was utilized to create mutations not in residues postulated to play a significant role in the enzymatic function or active site formation in manganese-binding proteins such as arginase. We have determined that the substitution of glycine for a histidine residue, located in a very highly conserved region of exon 3, and the substitution of a histidine and an aspartic acid residue within a similarly conserved region in exon 4, totally abolishes enzymatic activity. Mutations substituting glycine for an additional histidine and aspartic acid residue in exon 4 and two aspartic acid residues in exon 7 have also been created. We are currently in the process of characterizing these mutations.

  11. How Do Volcanoes Affect Human Life? Integrated Unit.

    ERIC Educational Resources Information Center

    Dayton, Rebecca; Edwards, Carrie; Sisler, Michelle

    This packet contains a unit on teaching about volcanoes. The following question is addressed: How do volcanoes affect human life? The unit covers approximately three weeks of instruction and strives to present volcanoes in an holistic form. The five subject areas of art, language arts, mathematics, science, and social studies are integrated into…

  12. Affective Man-Machine Interface: Unveiling Human Emotions through Biosignals

    NASA Astrophysics Data System (ADS)

    van den Broek, Egon L.; Lisý, Viliam; Janssen, Joris H.; Westerink, Joyce H. D. M.; Schut, Marleen H.; Tuinenbreijer, Kees

    As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological proce-sses, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals.

  13. Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals

    PubMed Central

    Panksepp, Jaak

    2011-01-01

    Background The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. Principal Findings The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as ‘rewards’ and ‘punishments’ in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher

  14. Human body contour data based activity recognition.

    PubMed

    Myagmarbayar, Nergui; Yuki, Yoshida; Imamoglu, Nevrez; Gonzalez, Jose; Otake, Mihoko; Yu, Wenwei

    2013-01-01

    This research work is aimed to develop autonomous bio-monitoring mobile robots, which are capable of tracking and measuring patients' motions, recognizing the patients' behavior based on observation data, and providing calling for medical personnel in emergency situations in home environment. The robots to be developed will bring about cost-effective, safe and easier at-home rehabilitation to most motor-function impaired patients (MIPs). In our previous research, a full framework was established towards this research goal. In this research, we aimed at improving the human activity recognition by using contour data of the tracked human subject extracted from the depth images as the signal source, instead of the lower limb joint angle data used in the previous research, which are more likely to be affected by the motion of the robot and human subjects. Several geometric parameters, such as, the ratio of height to weight of the tracked human subject, and distance (pixels) between centroid points of upper and lower parts of human body, were calculated from the contour data, and used as the features for the activity recognition. A Hidden Markov Model (HMM) is employed to classify different human activities from the features. Experimental results showed that the human activity recognition could be achieved with a high correct rate.

  15. Incorporating affective bias in models of human decision making

    NASA Technical Reports Server (NTRS)

    Nygren, Thomas E.

    1991-01-01

    Research on human decision making has traditionally focused on how people actually make decisions, how good their decisions are, and how their decisions can be improved. Recent research suggests that this model is inadequate. Affective as well as cognitive components drive the way information about relevant outcomes and events is perceived, integrated, and used in the decision making process. The affective components include how the individual frames outcomes as good or bad, whether the individual anticipates regret in a decision situation, the affective mood state of the individual, and the psychological stress level anticipated or experienced in the decision situation. A focus of the current work has been to propose empirical studies that will attempt to examine in more detail the relationships between the latter two critical affective influences (mood state and stress) on decision making behavior.

  16. Biologically active extracts with kidney affections applications

    NASA Astrophysics Data System (ADS)

    Pascu (Neagu), Mihaela; Pascu, Daniela-Elena; Cozea, Andreea; Bunaciu, Andrei A.; Miron, Alexandra Raluca; Nechifor, Cristina Aurelia

    2015-12-01

    This paper is aimed to select plant materials rich in bioflavonoid compounds, made from herbs known for their application performances in the prevention and therapy of renal diseases, namely kidney stones and urinary infections (renal lithiasis, nephritis, urethritis, cystitis, etc.). This paper presents a comparative study of the medicinal plant extracts composition belonging to Ericaceae-Cranberry (fruit and leaves) - Vaccinium vitis-idaea L. and Bilberry (fruit) - Vaccinium myrtillus L. Concentrated extracts obtained from medicinal plants used in this work were analyzed from structural, morphological and compositional points of view using different techniques: chromatographic methods (HPLC), scanning electronic microscopy, infrared, and UV spectrophotometry, also by using kinetic model. Liquid chromatography was able to identify the specific compounds of the Ericaceae family, present in all three extracts, arbutosid, as well as specific components of each species, mostly from the class of polyphenols. The identification and quantitative determination of the active ingredients from these extracts can give information related to their therapeutic effects.

  17. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions.

    PubMed

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant.

  18. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions

    PubMed Central

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant. PMID:26186596

  19. Human footprint affects US carbon balance more than climate change

    USGS Publications Warehouse

    Bachelet, Dominique; Ferschweiler, Ken; Sheehan, Tim; Baker, Barry; Sleeter, Benjamin M.; Zhu, Zhiliang

    2017-01-01

    The MC2 model projects an overall increase in carbon capture in conterminous United States during the 21st century while also simulating a rise in fire causing much carbon loss. Carbon sequestration in soils is critical to prevent carbon losses from future disturbances, and we show that natural ecosystems store more carbon belowground than managed systems do. Natural and human-caused disturbances affect soil processes that shape ecosystem recovery and competitive interactions between native, exotics, and climate refugees. Tomorrow's carbon budgets will depend on how land use, natural disturbances, and climate variability will interact and affect the balance between carbon capture and release.

  20. Cognitive Factors Affecting Freeze-like Behavior in Humans.

    PubMed

    Alban, Michael W; Pocknell, Victoria

    2017-01-01

    Contemporary research on survival-related defensive behaviors has identified physiological markers of freeze/flight/fight. Our research focused on cognitive factors associated with freeze-like behavior in humans. Study 1 tested if an explicit decision to freeze is associated with the psychophysiological state of freezing. Heart rate deceleration occurred when participants chose to freeze. Study 2 varied the efficacy of freezing relative to other defense options and found "freeze" was responsive to variations in the perceived effectiveness of alternative actions. Study 3 tested if individual differences in motivational orientation affect preference for a "freeze" option when the efficacy of options is held constant. A trend in the predicted direction suggested that naturally occurring cognitions led loss-avoiders to select "freeze" more often than reward-seekers. In combination, our attention to the cognitive factors affecting freeze-like behavior in humans represents a preliminary step in addressing an important but neglected research area.

  1. Human likeness: cognitive and affective factors affecting adoption of robot-assisted learning systems

    NASA Astrophysics Data System (ADS)

    Yoo, Hosun; Kwon, Ohbyung; Lee, Namyeon

    2016-07-01

    With advances in robot technology, interest in robotic e-learning systems has increased. In some laboratories, experiments are being conducted with humanoid robots as artificial tutors because of their likeness to humans, the rich possibilities of using this type of media, and the multimodal interaction capabilities of these robots. The robot-assisted learning system, a special type of e-learning system, aims to increase the learner's concentration, pleasure, and learning performance dramatically. However, very few empirical studies have examined the effect on learning performance of incorporating humanoid robot technology into e-learning systems or people's willingness to accept or adopt robot-assisted learning systems. In particular, human likeness, the essential characteristic of humanoid robots as compared with conventional e-learning systems, has not been discussed in a theoretical context. Hence, the purpose of this study is to propose a theoretical model to explain the process of adoption of robot-assisted learning systems. In the proposed model, human likeness is conceptualized as a combination of media richness, multimodal interaction capabilities, and para-social relationships; these factors are considered as possible determinants of the degree to which human cognition and affection are related to the adoption of robot-assisted learning systems.

  2. Global water resources affected by human interventions and climate change.

    PubMed

    Haddeland, Ingjerd; Heinke, Jens; Biemans, Hester; Eisner, Stephanie; Flörke, Martina; Hanasaki, Naota; Konzmann, Markus; Ludwig, Fulco; Masaki, Yoshimitsu; Schewe, Jacob; Stacke, Tobias; Tessler, Zachary D; Wada, Yoshihide; Wisser, Dominik

    2014-03-04

    Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future.

  3. Global water resources affected by human interventions and climate change

    PubMed Central

    Haddeland, Ingjerd; Heinke, Jens; Biemans, Hester; Eisner, Stephanie; Flörke, Martina; Hanasaki, Naota; Konzmann, Markus; Ludwig, Fulco; Masaki, Yoshimitsu; Schewe, Jacob; Stacke, Tobias; Tessler, Zachary D.; Wada, Yoshihide; Wisser, Dominik

    2014-01-01

    Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future. PMID:24344275

  4. Is it the real deal? Perception of virtual characters versus humans: an affective cognitive neuroscience perspective

    PubMed Central

    de Borst, Aline W.; de Gelder, Beatrice

    2015-01-01

    Recent developments in neuroimaging research support the increased use of naturalistic stimulus material such as film, avatars, or androids. These stimuli allow for a better understanding of how the brain processes information in complex situations while maintaining experimental control. While avatars and androids are well suited to study human cognition, they should not be equated to human stimuli. For example, the uncanny valley hypothesis theorizes that artificial agents with high human-likeness may evoke feelings of eeriness in the human observer. Here we review if, when, and how the perception of human-like avatars and androids differs from the perception of humans and consider how this influences their utilization as stimulus material in social and affective neuroimaging studies. First, we discuss how the appearance of virtual characters affects perception. When stimuli are morphed across categories from non-human to human, the most ambiguous stimuli, rather than the most human-like stimuli, show prolonged classification times and increased eeriness. Human-like to human stimuli show a positive linear relationship with familiarity. Secondly, we show that expressions of emotions in human-like avatars can be perceived similarly to human emotions, with corresponding behavioral, physiological and neuronal activations, with exception of physical dissimilarities. Subsequently, we consider if and when one perceives differences in action representation by artificial agents versus humans. Motor resonance and predictive coding models may account for empirical findings, such as an interference effect on action for observed human-like, natural moving characters. However, the expansion of these models to explain more complex behavior, such as empathy, still needs to be investigated in more detail. Finally, we broaden our outlook to social interaction, where virtual reality stimuli can be utilized to imitate complex social situations. PMID:26029133

  5. Is it the real deal? Perception of virtual characters versus humans: an affective cognitive neuroscience perspective.

    PubMed

    de Borst, Aline W; de Gelder, Beatrice

    2015-01-01

    Recent developments in neuroimaging research support the increased use of naturalistic stimulus material such as film, avatars, or androids. These stimuli allow for a better understanding of how the brain processes information in complex situations while maintaining experimental control. While avatars and androids are well suited to study human cognition, they should not be equated to human stimuli. For example, the uncanny valley hypothesis theorizes that artificial agents with high human-likeness may evoke feelings of eeriness in the human observer. Here we review if, when, and how the perception of human-like avatars and androids differs from the perception of humans and consider how this influences their utilization as stimulus material in social and affective neuroimaging studies. First, we discuss how the appearance of virtual characters affects perception. When stimuli are morphed across categories from non-human to human, the most ambiguous stimuli, rather than the most human-like stimuli, show prolonged classification times and increased eeriness. Human-like to human stimuli show a positive linear relationship with familiarity. Secondly, we show that expressions of emotions in human-like avatars can be perceived similarly to human emotions, with corresponding behavioral, physiological and neuronal activations, with exception of physical dissimilarities. Subsequently, we consider if and when one perceives differences in action representation by artificial agents versus humans. Motor resonance and predictive coding models may account for empirical findings, such as an interference effect on action for observed human-like, natural moving characters. However, the expansion of these models to explain more complex behavior, such as empathy, still needs to be investigated in more detail. Finally, we broaden our outlook to social interaction, where virtual reality stimuli can be utilized to imitate complex social situations.

  6. Phenyl valerate esterase activity of human butyrylcholinesterase.

    PubMed

    Mangas, Iris; Vilanova, Eugenio; Estévez, Jorge

    2017-03-15

    Phenyl valerate is used for detecting and measuring neuropathy target esterase (NTE) and has been used for discriminating esterases as potential target in hen model of organophosphorus delayed neuropathy. In previous studies we observed that phenyl valerate esterase (PVase) activity of an enzymatic fraction in chicken brain might be due to a butyrylcholinesterase protein (BuChE), and it was suggested that this enzymatic fraction could be related to the potentiation/promotion phenomenon of the organophosphate-induced delayed neuropathy (OPIDN). In this work, PVase activity of purified human butyrylcholinesterase (hBuChE) is demonstrated and confirms the novel observation that a relationship of BuChE with PVase activities is also relevant for humans, as is, therefore the potential role in toxicity for humans. The KM and catalytic constant (kcat) were estimated as 0.52/0.72 µM and 45,900/49,200 min(-1) respectively. Furthermore, this work studies the inhibition by preincubation of PVase and cholinesterase activities of hBuChE with irreversible inhibitors (mipafox, iso-OMPA or PMSF), showing that these inhibitors interact similarly in both activities with similar second-order inhibition constants. Acethylthiocholine and phenyl valerate partly inhibit PVase and cholinesterase activities, respectively. All these observations suggest that both activities occur in the same active center. The interaction with a reversible inhibitor (ethopropazine) showed that the cholinesterase activity was more sensitive than the PVase activity, showing that the sensitivity for this reversible inhibitor is affected by the nature of the substrate. The present work definitively establishes the capacity of BuChE to hydrolyze the carboxylester phenyl valerate using a purified enzyme (hBuChE). Therefore, BuChE should be considered in the research of organophosphorus targets of toxicity related with PVase proteins.

  7. Perinatal Oxidative Stress May Affect Fetal Ghrelin Levels in Humans.

    PubMed

    Luo, Zhong-Cheng; Bilodeau, Jean-François; Nuyt, Anne Monique; Fraser, William D; Julien, Pierre; Audibert, Francois; Xiao, Lin; Garofalo, Carole; Levy, Emile

    2015-12-08

    In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24-28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p < 0.0001). Adjusting for gestational age at blood sampling, cord plasma ghrelin concentrations were consistently negatively correlated to oxidative stress biomarkers in maternal (r = -0.32, p < 0.0001 for MDA; r = -0.31, p < 0.0001 for F2-isoprostanes) or cord plasma (r = -0.13, p = 0.04 for MDA; r = -0.32, p < 0.0001 for F2-isoprostanes). Other fetal metabolic health biomarkers were not correlated to oxidative stress. Adjusting for maternal and pregnancy characteristics, similar associations were observed. Our study provides the first preliminary evidence suggesting that oxidative stress may affect fetal ghrelin levels in humans. The implications in developmental "programming" the vulnerability to metabolic syndrome related disorders remain to be elucidated.

  8. Humanized Foxp2 specifically affects cortico-basal ganglia circuits.

    PubMed

    Reimers-Kipping, S; Hevers, W; Pääbo, S; Enard, W

    2011-02-23

    It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution and influence aspects of speech and language. Recently it was shown that when these substitutions are introduced into the endogenous Foxp2 gene of mice, they increase dendrite length and long-term depression (LTD) in medium spiny neurons of the striatum. Here we investigated if these effects are found in other brain regions. We found that neurons in the cerebral cortex, the thalamus and the striatum have increased dendrite lengths in the humanized mice whereas neurons in the amygdala and the cerebellum do not. In agreement with previous work we found increased LTD in medium spiny neurons, but did not detect alterations of synaptic plasticity in Purkinje cells. We conclude that although Foxp2 is expressed in many brain regions and has multiple roles during mammalian development, the evolutionary changes that occurred in the protein in human ancestors specifically affect brain regions that are connected via cortico-basal ganglia circuits.

  9. Corrugator activity confirms immediate negative affect in surprise

    PubMed Central

    Topolinski, Sascha; Strack, Fritz

    2015-01-01

    The emotion of surprise entails a complex of immediate responses, such as cognitive interruption, attention allocation to, and more systematic processing of the surprising stimulus. All these processes serve the ultimate function to increase processing depth and thus cognitively master the surprising stimulus. The present account introduces phasic negative affect as the underlying mechanism responsible for this switch in operating mode. Surprising stimuli are schema-discrepant and thus entail cognitive disfluency, which elicits immediate negative affect. This affect in turn works like a phasic cognitive tuning switching the current processing mode from more automatic and heuristic to more systematic and reflective processing. Directly testing the initial elicitation of negative affect by surprising events, the present experiment presented high and low surprising neutral trivia statements to N = 28 participants while assessing their spontaneous facial expressions via facial electromyography. High compared to low surprising trivia elicited higher corrugator activity, indicative of negative affect and mental effort, while leaving zygomaticus (positive affect) and frontalis (cultural surprise expression) activity unaffected. Future research shall investigate the mediating role of negative affect in eliciting surprise-related outcomes. PMID:25762956

  10. Sex differences in the brain response to affective scenes with or without humans.

    PubMed

    Proverbio, Alice Mado; Adorni, Roberta; Zani, Alberto; Trestianu, Laura

    2009-10-01

    Recent findings have demonstrated that women might be more reactive than men to viewing painful stimuli (vicarious response to pain), and therefore more empathic [Han, S., Fan, Y., & Mao, L. (2008). Gender difference in empathy for pain: An electrophysiological investigation. Brain Research, 1196, 85-93]. We investigated whether the two sexes differed in their cerebral responses to affective pictures portraying humans in different positive or negative contexts compared to natural or urban scenarios. 440 IAPS slides were presented to 24 Italian students (12 women and 12 men). Half the pictures displayed humans while the remaining scenes lacked visible persons. ERPs were recorded from 128 electrodes and swLORETA (standardized weighted Low-Resolution Electromagnetic Tomography) source reconstruction was performed. Occipital P115 was greater in response to persons than to scenes and was affected by the emotional valence of the human pictures. This suggests that processing of biologically relevant stimuli is prioritized. Orbitofrontal N2 was greater in response to positive than negative human pictures in women but not in men, and not to scenes. A late positivity (LP) to suffering humans far exceeded the response to negative scenes in women but not in men. In both sexes, the contrast suffering-minus-happy humans revealed a difference in the activation of the occipito/temporal, right occipital (BA19), bilateral parahippocampal, left dorsal prefrontal cortex (DPFC) and left amygdala. However, increased right amygdala and right frontal area activities were observed only in women. The humans-minus-scenes contrast revealed a difference in the activation of the middle occipital gyrus (MOG) in men, and of the left inferior parietal (BA40), left superior temporal gyrus (STG, BA38) and right cingulate (BA31) in women (270-290 ms). These data indicate a sex-related difference in the brain response to humans, possibly supporting human empathy.

  11. Human Empathy, Personality and Experience Affect the Emotion Ratings of Dog and Human Facial Expressions.

    PubMed

    Kujala, Miiamaaria V; Somppi, Sanni; Jokela, Markus; Vainio, Outi; Parkkonen, Lauri

    2017-01-01

    Facial expressions are important for humans in communicating emotions to the conspecifics and enhancing interpersonal understanding. Many muscles producing facial expressions in humans are also found in domestic dogs, but little is known about how humans perceive dog facial expressions, and which psychological factors influence people's perceptions. Here, we asked 34 observers to rate the valence, arousal, and the six basic emotions (happiness, sadness, surprise, disgust, fear, and anger/aggressiveness) from images of human and dog faces with Pleasant, Neutral and Threatening expressions. We investigated how the subjects' personality (the Big Five Inventory), empathy (Interpersonal Reactivity Index) and experience of dog behavior affect the ratings of dog and human faces. Ratings of both species followed similar general patterns: human subjects classified dog facial expressions from pleasant to threatening very similarly to human facial expressions. Subjects with higher emotional empathy evaluated Threatening faces of both species as more negative in valence and higher in anger/aggressiveness. More empathetic subjects also rated the happiness of Pleasant humans but not dogs higher, and they were quicker in their valence judgments of Pleasant human, Threatening human and Threatening dog faces. Experience with dogs correlated positively with ratings of Pleasant and Neutral dog faces. Personality also had a minor effect on the ratings of Pleasant and Neutral faces in both species. The results imply that humans perceive human and dog facial expression in a similar manner, and the perception of both species is influenced by psychological factors of the evaluators. Especially empathy affects both the speed and intensity of rating dogs' emotional facial expressions.

  12. Human Empathy, Personality and Experience Affect the Emotion Ratings of Dog and Human Facial Expressions

    PubMed Central

    Kujala, Miiamaaria V.; Somppi, Sanni; Jokela, Markus; Vainio, Outi; Parkkonen, Lauri

    2017-01-01

    Facial expressions are important for humans in communicating emotions to the conspecifics and enhancing interpersonal understanding. Many muscles producing facial expressions in humans are also found in domestic dogs, but little is known about how humans perceive dog facial expressions, and which psychological factors influence people’s perceptions. Here, we asked 34 observers to rate the valence, arousal, and the six basic emotions (happiness, sadness, surprise, disgust, fear, and anger/aggressiveness) from images of human and dog faces with Pleasant, Neutral and Threatening expressions. We investigated how the subjects’ personality (the Big Five Inventory), empathy (Interpersonal Reactivity Index) and experience of dog behavior affect the ratings of dog and human faces. Ratings of both species followed similar general patterns: human subjects classified dog facial expressions from pleasant to threatening very similarly to human facial expressions. Subjects with higher emotional empathy evaluated Threatening faces of both species as more negative in valence and higher in anger/aggressiveness. More empathetic subjects also rated the happiness of Pleasant humans but not dogs higher, and they were quicker in their valence judgments of Pleasant human, Threatening human and Threatening dog faces. Experience with dogs correlated positively with ratings of Pleasant and Neutral dog faces. Personality also had a minor effect on the ratings of Pleasant and Neutral faces in both species. The results imply that humans perceive human and dog facial expression in a similar manner, and the perception of both species is influenced by psychological factors of the evaluators. Especially empathy affects both the speed and intensity of rating dogs’ emotional facial expressions. PMID:28114335

  13. Do ELF magnetic fields affect human reaction time?

    SciTech Connect

    Podd, J.V.; Whittington, C.J.; Barnes, G.R.G.; Page, W.H.; Rapley, B.I.

    1995-12-01

    Two double-blind studies were run in an attempt to confirm the finding that a 0.2 Hz magnetic field affects simple reaction time (RT) in humans, whereas a 0.1 Hz field does not. In the first experiment, 12 volunteer subjects were exposed to a continuous 0.2 Hz, 0.1 Hz, or sham field in a fully counter-balanced, within-subjects design. Subjects were run singly for one condition each day over 3 consecutive days with a field strength of 1.1 mT and a daily expose duration of 5 min. Neither magnetic field had any effect on RT at any time during the exposure. One condition of a second study, using a new group of 24 volunteer subjects, also failed to find any field effects at 0.2 Hz. Additionally, the second study failed to show any effects when the frequency, flux density, and field orientation were set according to parameter resonance theory. It is suggested that, although ELF magnetic field effects on human behavior may be elusive, future research can improve detection rates by paying greater attention to reducing error variance and increasing statistical power.

  14. Has solar variability caused climate change that affected human culture?

    NASA Astrophysics Data System (ADS)

    Feynman, Joan

    If solar variability affects human culture it most likely does so by changing the climate in which the culture operates. Variations in the solar radiative input to the Earth's atmosphere have often been suggested as a cause of such climate change on time scales from decades to tens of millennia. In the last 20 years there has been enormous progress in our knowledge of the many fields of research that impinge on this problem; the history of the solar output, the effect of solar variability on the Earth's mean climate and its regional patterns, the history of the Earth's climate and the history of mankind and human culture. This new knowledge encourages revisiting the question asked in the title of this talk. Several important historical events have been reliably related to climate change including the Little Ice Age in northern Europe and the collapse of the Classical Mayan civilization in the 9th century AD. In the first section of this paper we discus these historical events and review the evidence that they were caused by changes in the solar output. Perhaps the most important event in the history of mankind was the development of agricultural societies. This began to occur almost 12,000 years ago when the climate changed from the Pleistocene to the modern climate of the Holocene. In the second section of the paper we will discuss the suggestion ( Feynman and Ruzmaikin, 2007) that climate variability was the reason agriculture developed when it did and not before.

  15. Design and Development of an Affective Interface for Supporting Energy-saving Activities and its Evaluation

    NASA Astrophysics Data System (ADS)

    Ito, Kyoko; Tomita, Daisuke; Imaki, Tomotaka; Hongo, Taishiro; Yoshikawa, Hidekazu

    Toward a sustainable society, energy and environmental issues are very important and controversial problems, and it is expected to support various human activities for the measures by using Information Technology. The purpose of this study is to develop an affective interface for supporting people's energy-saving activities. First, a model for supporting people's energy-saving activities involving affective elements has been constructed for supporting people's energy-saving activities, based on social psychological approaches. Based on the proposed model, the requirements on an affective interface for people's energy-saving activities have been considered. In this study, the affective interface presents suitable energy-saving activities and current electric energy consumption by a character agent with a graphical shape and synthesized voice. The character agent recommends people's energy-saving activities, tells the method of energy-saving activities and the effectiveness, and so on. The affective interface for supporting energy-saving activities has been designed in detail and developed. Then, the evaluation experiment of the developed interface has been conducted, and the results of the experiments were analyzed.

  16. 16 CFR 801.3 - Activities in or affecting commerce.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Activities in or affecting commerce. 801.3 Section 801.3 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.3...

  17. 16 CFR 801.3 - Activities in or affecting commerce.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Activities in or affecting commerce. 801.3 Section 801.3 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.3...

  18. 16 CFR 801.3 - Activities in or affecting commerce.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Activities in or affecting commerce. 801.3 Section 801.3 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.3...

  19. 16 CFR 801.3 - Activities in or affecting commerce.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Activities in or affecting commerce. 801.3 Section 801.3 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.3...

  20. 16 CFR 801.3 - Activities in or affecting commerce.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Activities in or affecting commerce. 801.3 Section 801.3 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.3...

  1. Monitoring Affect States during Effortful Problem Solving Activities

    ERIC Educational Resources Information Center

    D'Mello, Sidney K.; Lehman, Blair; Person, Natalie

    2010-01-01

    We explored the affective states that students experienced during effortful problem solving activities. We conducted a study where 41 students solved difficult analytical reasoning problems from the Law School Admission Test. Students viewed videos of their faces and screen captures and judged their emotions from a set of 14 states (basic…

  2. Determinants affecting physical activity levels in animal models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C L.; Wade, Charles E.

    2002-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  3. Determinants Affecting Physical Activity Levels In Animal Models

    NASA Technical Reports Server (NTRS)

    Tou, Janet C. L.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play all underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multi-factorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked making it difficult to determine whether a single, combination or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to tile ventral medial hypothalamus and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.

  4. Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise.

    PubMed

    Apró, William; Moberg, Marcus; Hamilton, D Lee; Ekblom, Björn; Rooyackers, Olav; Holmberg, Hans-Christer; Blomstrand, Eva

    2015-10-01

    We examined how the stimulatory effect of leucine on the mechanistic target of rapamycin complex 1 (mTORC1) pathway is affected by the presence of the remaining essential amino acids (EAAs). Nine male subjects performed resistance exercise on 4 occasions and were randomly supplied EAAs with leucine, EAAs without leucine (EAA-Leu), leucine alone, or flavored water (placebo; control). Muscle biopsies were taken from the vastus lateralis before and 60 and 90 min after exercise. Biopsies were analyzed for protein phosphorylation, kinase activity, protein-protein interactions, amino acid concentrations, and tracer incorporation. Leucine alone stimulated ribosomal protein s6 kinase 1 (S6K1) phosphorylation ∼280% more than placebo and EAA-Leu after exercise. Moreover, this response was enhanced by 60-75% after intake of EAAs compared with that of leucine alone (P < 0.05). Kinase activity of S6K1 reflected that of S6K1 phosphorylation; 60 min after exercise, the activity was elevated 3.3- and 4.2-fold with intake of leucine alone and with EAAs, respectively (P < 0.05). The interaction between mammalian target of rapamycin and regulatory-associated protein of mammalian target of rapamycin was unaltered in response to both resistance exercise and amino acid provision. Leucine alone stimulates mTORC1 signaling, although this response is enhanced by other EAAs and does not appear to be caused by alterations in mTORC1 assembly.

  5. Human monocyte differentiation stage affects response to arachidonic acid.

    PubMed

    Escobar-Alvarez, Elizabeth; Pelaez, Carlos A; García, Luis F; Rojas, Mauricio

    2010-01-01

    AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.

  6. Temperature Affects Human Sweet Taste via At Least Two Mechanisms.

    PubMed

    Green, Barry G; Nachtigal, Danielle

    2015-07-01

    The reported effects of temperature on sweet taste in humans have generally been small and inconsistent. Here, we describe 3 experiments that follow up a recent finding that cooling from 37 to 21 °C does not reduce the initial sweetness of sucrose but increases sweet taste adaptation. In experiment 1, subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5-41 °C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre-exposures to the same solutions or to H2O; experiment 2 compared the effects of temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame, and saccharin); and experiment 3 employed a flow-controlled gustometer to rule out the possibility the effects of temperature in the preceding experiments were unique to dipping the tongue into a still taste solution. The results (i) confirmed that mild cooling does not attenuate sweetness but can increase sweet taste adaptation; (ii) demonstrated that cooling to 5-12 °C can directly reduce sweetness intensity; and (iii) showed that both effects vary across stimuli. These findings have implications for the TRPM5 hypothesis of thermal effects on sweet taste and raise the possibility that temperature also affects an earlier step in the T1R2-T1R3 transduction cascade.

  7. Temperature Affects Human Sweet Taste via At Least Two Mechanisms

    PubMed Central

    Nachtigal, Danielle

    2015-01-01

    The reported effects of temperature on sweet taste in humans have generally been small and inconsistent. Here, we describe 3 experiments that follow up a recent finding that cooling from 37 to 21 °C does not reduce the initial sweetness of sucrose but increases sweet taste adaptation. In experiment 1, subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5–41 °C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre-exposures to the same solutions or to H2O; experiment 2 compared the effects of temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame, and saccharin); and experiment 3 employed a flow-controlled gustometer to rule out the possibility the effects of temperature in the preceding experiments were unique to dipping the tongue into a still taste solution. The results (i) confirmed that mild cooling does not attenuate sweetness but can increase sweet taste adaptation; (ii) demonstrated that cooling to 5–12 °C can directly reduce sweetness intensity; and (iii) showed that both effects vary across stimuli. These findings have implications for the TRPM5 hypothesis of thermal effects on sweet taste and raise the possibility that temperature also affects an earlier step in the T1R2–T1R3 transduction cascade. PMID:25963040

  8. Asymmetric frontal cortical activity and negative affective responses to ostracism.

    PubMed

    Peterson, Carly K; Gravens, Laura C; Harmon-Jones, Eddie

    2011-06-01

    Ostracism arouses negative affect. However, little is known about variables that influence the intensity of these negative affective responses. Two studies fill this void by incorporating work on approach- and withdrawal-related emotional states and their associated cortical activations. Study 1 found that following ostracism anger related directly to relative left frontal cortical activation. Study 2 used unilateral hand contractions to manipulate frontal cortical activity prior to an ostracizing event. Right-hand contractions, compared to left-hand contractions, caused greater relative left frontal cortical activation during the hand contractions as well as ostracism. Also, right-hand contractions caused more self-reported anger in response to being ostracized. Within-condition correlations revealed patterns of associations between ostracism-induced frontal asymmetry and emotive responses to ostracism consistent with Study 1. Taken together, these results suggest that asymmetrical frontal cortical activity is related to angry responses to ostracism, with greater relative left frontal cortical activity being associated with increased anger.

  9. Telomerase activity in human cancer

    SciTech Connect

    Griffith, J.

    2000-10-01

    The overall goal of this collaborative project was to investigate the role in malignant cells of both chromosome telomeres, and telomerase, the enzyme that replicates telomeres. Telomeres are highly conserved nucleoprotein complexes located at the ends of eucaryotic chromosomes. Telomere length in somatic cells is reduced by 40--50 nucleotide pairs with every cell division due to incomplete replication of terminal DNA sequences and the absence of telomerase, the ribonucleoprotein that adds telomere DNA to chromosome ends. Although telomerase is active in cells with extended proliferative capacities, including more than 85% of tumors, work performed under this contract demonstrated that the telomeres of human cancer cells are shorter than those of paired normal cells, and that the length of the telomeres is characteristic of particular types of cancers. The extent of telomere shortening ostensibly is related to the number of cell divisions the tumor has undergone. It is believed that ongoing cell proliferation leads to the accumulation and fixation of new mutations in tumor cell lineages.Therefore, it is not unreasonable to assume that the degree of phenotypic variability is related to the proliferative history of the tumor, and therefore to telomere length, implying a correlation with prognosis. In some human tumors, short telomeres are also correlated with genomic instabilities, including interstitial chromosome translocation, loss of heterozygosity, and aneuoploidy. Moreover, unprotected chromosome ends are highly recombinogenic and telomere shortening in cultured human cells correlates with the formation of dicentric chromosomes, suggesting that critically short telomeres not only identify, but also predispose, cells to genomic instability, again implying a correlation with prognosis. Therefore, telomere length or content could be an important predictor of metastatic potential or responsiveness to various therapeutic modalities.

  10. Factors affecting farm noise during common agricultural activities.

    PubMed

    Franklin, R C; Depczynski, J; Challinor, K; Williams, W; Fragar, L J

    2006-05-01

    Hearing injury due to exposure to excessive noise during common farming activities is a significant problem for farmers. The aim of this study was to investigate factors that affect the level of risk to hearing caused by common farming activities. Noise levels on farms were measured across a range of activities and producer groups, and situational factors that effect noise levels were also investigated. Older tractors were found to be 6 dB louder than newer tractors. Cabs reduced noise to the operator by 16 dB, which was halved to 8 dB if a door was open. Radios added between 3 and 5 dB to the noise in the cab. These variables significantly affect the noise level at the ear of operators and others in the workplace, and affect the subsequent exposure limits that are considered safe. Situational factors need to be considered in assessing the level of risk to farmers' hearing and in choosing noise management strategies on the farm. This information has been incorporated into material about hearing and discussions with farmers who participated in field day hearing screening programs in Australia.

  11. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    SciTech Connect

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  12. Melatonin differentially affects vascular blood flow in humans.

    PubMed

    Cook, Jonathan S; Sauder, Charity L; Ray, Chester A

    2011-02-01

    Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial Doppler), arterial blood pressure, and heart rate were measured in 10 healthy subjects (29±1 yr; 5 men and 5 women) in the supine position for 3 min. The protocol began 45 min after the ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the other substance. Melatonin did not alter heart rate and mean arterial pressure. Renal blood flow velocity (RBFV) and renal vascular conductance (RVC) were lower during the melatonin trial compared with placebo (RBFV, 40.5±2.9 vs. 45.4±1.5 cm/s; and RVC, 0.47±0.02 vs. 0.54±0.01 cm·s(-1)·mmHg(-1), respectively). In contrast, forearm blood flow (FBF) and forearm vascular conductance (FVC) were greater with melatonin compared with placebo (FBF, 2.4±0.2 vs. 1.9±0.1 ml·100 ml(-1)·min(-1); and FVC, 0.029±0.003 vs. 0.023±0.002 arbitrary units, respectively). Melatonin did not alter cerebral blood flow measurements compared with placebo. Additionally, phentolamine (5-mg bolus) after melatonin reversed the decrease in RVC, suggesting that melatonin increases sympathetic outflow to the kidney to mediate renal vasoconstriction. In summary, exogenous melatonin differentially alters vascular blood flow in humans. These data suggest the complex nature of melatonin on the vasculature in humans.

  13. Visual stimulus eccentricity affects human gamma peak frequency.

    PubMed

    van Pelt, Stan; Fries, Pascal

    2013-09-01

    The peak frequency of neuronal gamma-band synchronization has received much attention in recent years. Gamma peak frequency shifts to higher frequency values for higher contrast, faster moving, and attended stimuli. In monkey V1, gamma peak frequency for a drifting grating is higher for a parafoveal as compared to an eccentric stimulus (Lima et al., 2010). This effect might be due to the cortical magnification factor: the higher cortical magnification for parafoveal stimuli increases the velocity with which the cortical representations of the moving grating stripes move across the cortical surface. Since faster moving stimuli lead to higher gamma frequency, a faster moving cortical representation might do the same. This explanation predicts that the eccentricity effect on gamma peak frequency is absent for stationary stimuli. To test this, we investigated the effect of eccentricity on gamma peak frequency by recording magnetoencephalography in human subjects while they viewed moving or stationary gratings. We found that both the moving and the stationary stimuli induced lower peak frequencies for larger eccentricities, arguing against an explanation based on the cortical magnification factor. We further investigated whether this eccentricity effect was explained by differences in the size or the spatial frequency of the expected cortical activation. Neither of those explained the eccentricity effect. We propose that the different stimulus and top-down factors leading to higher gamma peak frequency all result in higher stimulus salience, that salience is translated into gamma peak frequency, and that gamma peak frequency might subserve the preferential processing of neuronal activity induced by salient stimuli.

  14. Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

    PubMed Central

    Cools, Roshan; Nakamura, Kae; Daw, Nathaniel D

    2011-01-01

    Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin—comprising both affective and activational ones, as well as a number of other functions not overtly related to either—can be seen as consequences of a single root mechanism. PMID:20736991

  15. MISR Satellite Observations of Aerosol Types Affecting Human Health

    NASA Astrophysics Data System (ADS)

    Kalashnikova, O. V.; Franklin, M.; Garay, M. J.; Diner, D. J.

    2015-12-01

    Ground-based observations of pollutants and concentrations of particulate matter (PM), that includes small particles designated PM2.5 and dust-dominated PM10, are the gold standard in studies of environmental impacts on human health. However, because monitoring stations are costly, they typically provide only limited spatial coverage, especially in rural and remote areas. We will demonstrate how data from the Multi-angle Imaging SpectroRadiometer (MISR) instrument that has been flying on NASA's Terra Earth Observing System satellite since early 2000 can be used to provide estimates of surface PM types. The current MISR operational aerosol retrieval uses a combination of multi-spectral and multi-angle data to retrieve aerosol optical depth (AOD) and particle property information (including dust AOD) globally at 17.6 km spatial resolution. Using the same algorithm with data collected in all 36-channels at 275 m resolution (Local Mode), which is available over greater Los Angeles area, and also was activated during 2013 DISCOVER-AQ California field campaign, high-resolution 4.4 km aerosol retrievals were performed in addition to the standard 17.6 km retrievals. The 4.4 km spatial resolution of the PM information data is fine enough to be able to resolve local differences in PM loading that may be important for understanding regional health effects of pollution in the region. In particular, we demonstrate that MISR high-resolution AOD retrievals are in better agreement with ground-based aerosol observations and reveal more details about the aerosol spatial variability compared to the MISR standard 17.6 km product. Then we will discuss techniques and show examples of the application of high-resolution MISR data to provide estimates of surface PM for the greater Los Angeles area in 2008 and for California San Joaquin Valley during the 2013 DISCOVER-AQ field campaign. Finally, we will discuss future NASA instruments that will provide new information allowing for better

  16. Oxalomalate affects the inducible nitric oxide synthase expression and activity.

    PubMed

    Irace, Carlo; Esposito, Giuseppe; Maffettone, Carmen; Rossi, Antonietta; Festa, Michela; Iuvone, Teresa; Santamaria, Rita; Sautebin, Lidia; Carnuccio, Rosa; Colonna, Alfredo

    2007-03-13

    Inducible nitric oxide synthase (iNOS) is an homodimeric enzyme which produces large amounts of nitric oxide (NO) in response to inflammatory stimuli. Several factors affect the synthesis and catalytic activity of iNOS. Particularly, dimerization of NOS monomers is promoted by heme, whereas an intracellular depletion of heme and/or L-arginine considerably decreases NOS resistance to proteolysis. In this study, we found that oxalomalate (OMA, oxalomalic acid, alpha-hydroxy-beta-oxalosuccinic acid), an inhibitor of both aconitase and NADP-dependent isocitrate dehydrogenase, inhibited nitrite production and iNOS protein expression in lipopolysaccharide (LPS)-activated J774 macrophages, without affecting iNOS mRNA content. Furthermore, injection of OMA precursors to LPS-stimulated rats also decreased nitrite production and iNOS expression in isolated peritoneal macrophages. Interestingly, alpha-ketoglutarate or succinyl-CoA administration reversed OMA effect on NO production, thus correlating NO biosynthesis with the anabolic capacity of Krebs cycle. When protein synthesis was blocked by cycloheximide in LPS-activated J774 cells treated with OMA, iNOS protein levels, evaluated by Western blot analysis and (35)S-metabolic labelling, were decreased, suggesting that OMA reduces iNOS biosynthesis and induces an increase in the degradation rate of iNOS protein. Moreover, we showed that OMA inhibits the activity of the iNOS from lung of LPS-treated rats by enzymatic assay. Our results, demonstrating that OMA acts regulating synthesis, catalytic activity and degradation of iNOS, suggest that this compound might have a potential role in reducing the NO overproduction occurring in some pathological conditions.

  17. Alteration of membrane phospholipid methylation by adenosine analogs does not affect T lymphocyte activation

    SciTech Connect

    Gormand, F.; Pacheco, Y. ); Fonlupt, P. ); Revillard, J.P. )

    1990-01-01

    Membrane phospholipid methylation has been described during activation of various immune cells. Moreover recent data indicated modulation of immune cells functions by adenosine. As S-adenosyl-methionine and S-adenosyl-homocysteine are adenosine analogs and modulators of transmethylation reactions, the effects of SAH and SAM were investigated on membrane phospholipid methylation and lymphocyte activation. SAM was shown to induce the membrane phospholipid methylation as assessed by the {sup 3}Hmethyl-incorporation in membrane extract. This effect was inhibited by SAH. In contrast SAM and SAH did not affect the phytohemagglutinin-induced proliferative response of peripheral blood mononuclear cells. SAH neither modified the early internalization of membrane CD3 antigens nor did it prevent the late expression of HLA-DR antigens on lymphocytes activated by phytohemagglutinin. These results indicate that in vitro alteration of phospholipid methylation does not affect subsequent steps of human T lymphocyte activation and proliferation.

  18. Activities affecting surface water resources: A general overview

    SciTech Connect

    Not Available

    1990-01-01

    In November 1987, P.E.I. signed a federal/provincial work-sharing arrangement on water resource management focusing on groundwater pollution, surface water degradation and estuarine eutrophication. The surface water program was designed to identify current surface water uses and users within 12 major watersheds across the Island containing 26 individual rivers, as well as problems arising due to practices that degrade the quality of surface water and restricts its value to other user groups. This report presents a general overview of the program, covering the general characteristics of the Island; operations in agriculture, fish and wildlife, forestry, recreation, fisheries, and industry; alterations of natural features of waterways; wetlands; additional watershed activities such as hydrometric stations and subdivision development; and activities affecting surface water resources such as sedimentation sources, pollution point sources and instream obstructions.

  19. Intolerance of uncertainty correlates with insula activation during affective ambiguity

    PubMed Central

    Simmons, Alan; Matthews, Scott C.; Paulus, Martin P.; Stein, Murray B.

    2009-01-01

    Intolerance of uncertainty (IU), or the increased affective response to situations with uncertain outcomes, is an important component process of anxiety disorders. Increased IU is observed in panic disorder (PD), obsessive compulsive disorder (OCD) and generalized anxiety disorder (GAD), and is thought to relate to dysfunctional behaviors and thought patterns in these disorders. Identifying what brain systems are associated with IU would contribute to a comprehensive model of anxiety processing, and increase our understanding of the neurobiology of anxiety disorders. Here, we used a behavioral task, Wall of Faces (WOF), during functional magnetic resonance imaging (fMRI), which probes both affect and ambiguity, to examine the neural circuitry of IU in fourteen (10 females) college age (18.8 yrs) subjects. All subjects completed the Intolerance of Uncertainty Scale (IUS), Anxiety Sensitivity Index (ASI), and a measure of neuroticism (i.e. the NEO-N). IUS scores but neither ASI nor NEO-N scores, correlated positively with activation in bilateral insula during affective ambiguity. Thus, the experience of IU during certain types of emotion processing may relate to the degree to which bilateral insula processes uncertainty. Previously observed insula hyperactivity in anxiety disorder individuals may therefore be directly linked to altered processes of uncertainty. PMID:18079060

  20. Intolerance of uncertainty correlates with insula activation during affective ambiguity.

    PubMed

    Simmons, Alan; Matthews, Scott C; Paulus, Martin P; Stein, Murray B

    2008-01-10

    Intolerance of uncertainty (IU), or the increased affective response to situations with uncertain outcomes, is an important component process of anxiety disorders. Increased IU is observed in panic disorder (PD), obsessive compulsive disorder (OCD) and generalized anxiety disorder (GAD), and is thought to relate to dysfunctional behaviors and thought patterns in these disorders. Identifying what brain systems are associated with IU would contribute to a comprehensive model of anxiety processing, and increase our understanding of the neurobiology of anxiety disorders. Here, we used a behavioral task, Wall of Faces (WOFs), during functional magnetic resonance imaging (fMRI), which probes both affect and ambiguity, to examine the neural circuitry of IU in 14 (10 females) college age (18.8 years) subjects. All subjects completed the Intolerance of Uncertainty Scale (IUS), Anxiety Sensitivity Index (ASI), and a measure of neuroticism (i.e. the NEO-N). IUS scores but neither ASI nor NEO-N scores, correlated positively with activation in bilateral insula during affective ambiguity. Thus, the experience of IU during certain types of emotion processing may relate to the degree to which bilateral insula processes uncertainty. Previously observed insula hyperactivity in anxiety disorder individuals may therefore be directly linked to altered processes of uncertainty.

  1. Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear.

    PubMed

    Pissiota, Anna; Frans, Orjan; Michelgård, Asa; Appel, Lieuwe; Långström, Bengt; Flaten, Magne Arve; Fredrikson, Mats

    2003-09-01

    The human startle response is modulated by emotional experiences, with startle potentiation associated with negative affect. We used positron emission tomography with 15O-water to study neural networks associated with startle modulation by phobic fear in a group of subjects with specific snake or spider phobia, but not both, during exposure to pictures of their feared and non-feared objects, paired and unpaired with acoustic startle stimuli. Measurement of eye electromyographic activity confirmed startle potentiation during the phobic as compared with the non-phobic condition. Employing a factorial design, we evaluated brain correlates of startle modulation as the interaction between startle and affect, using the double subtraction contrast (phobic startle vs. phobic alone) vs. (non-phobic startle vs. non-phobic alone). As a result of startle potentiation, a significant increase in regional cerebral blood flow was found in the left amygdaloid-hippocampal region, and medially in the affective division of the anterior cingulate cortex (ACC). These results provide evidence from functional brain imaging for a modulatory role of the amygdaloid complex on startle reactions in humans. They also point to the involvement of the affective ACC in the processing of startle stimuli during emotionally aversive experiences. The co-activation of these areas may reflect increased attention to fear-relevant stimuli. Thus, we suggest that the amygdaloid area and the ACC form part of a neural system dedicated to attention and orientation to danger, and that this network modulates startle during negative affect.

  2. Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming.

    PubMed

    Li, Heng-Hong; Wang, Yi-Wen; Chen, Renxiang; Zhou, Bin; Ashwell, Jonathan D; Fornace, Albert J

    2015-01-01

    Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures.

  3. City living and urban upbringing affect neural social stress processing in humans.

    PubMed

    Lederbogen, Florian; Kirsch, Peter; Haddad, Leila; Streit, Fabian; Tost, Heike; Schuch, Philipp; Wüst, Stefan; Pruessner, Jens C; Rietschel, Marcella; Deuschle, Michael; Meyer-Lindenberg, Andreas

    2011-06-22

    More than half of the world's population now lives in cities, making the creation of a healthy urban environment a major policy priority. Cities have both health risks and benefits, but mental health is negatively affected: mood and anxiety disorders are more prevalent in city dwellers and the incidence of schizophrenia is strongly increased in people born and raised in cities. Although these findings have been widely attributed to the urban social environment, the neural processes that could mediate such associations are unknown. Here we show, using functional magnetic resonance imaging in three independent experiments, that urban upbringing and city living have dissociable impacts on social evaluative stress processing in humans. Current city living was associated with increased amygdala activity, whereas urban upbringing affected the perigenual anterior cingulate cortex, a key region for regulation of amygdala activity, negative affect and stress. These findings were regionally and behaviourally specific, as no other brain structures were affected and no urbanicity effect was seen during control experiments invoking cognitive processing without stress. Our results identify distinct neural mechanisms for an established environmental risk factor, link the urban environment for the first time to social stress processing, suggest that brain regions differ in vulnerability to this risk factor across the lifespan, and indicate that experimental interrogation of epidemiological associations is a promising strategy in social neuroscience.

  4. Transmission distortion affecting human noncrossover but not crossover recombination: a hidden source of meiotic drive.

    PubMed

    Odenthal-Hesse, Linda; Berg, Ingrid L; Veselis, Amelia; Jeffreys, Alec J; May, Celia A

    2014-02-01

    Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream. To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C) over weak (A/T) base pairs as might be predicted from the well-established correlations between high GC content and recombination activity in mammalian genomes.

  5. Zinc supplementation affects the activity patterns of rural Guatemalan infants.

    PubMed

    Bentley, M E; Caulfield, L E; Ram, M; Santizo, M C; Hurtado, E; Rivera, J A; Ruel, M T; Brown, K H

    1997-07-01

    Zinc deficiency has been associated with growth deficits, reduced dietary intake and appetite, and has been hypothesized to result in reduced activity. This randomized, double-blind, placebo-controlled study examined whether 10 mg of oral zinc as zinc sulfate, given daily for up to 7 mo, affected activity patterns of 85 Guatemalan infants recruited at 6-9 mo of age. Infant activity was assessed by time sampling-observation method at 10-min intervals during a 12-h data collection period, at base line, 3 and 7 mo follow-up. Motor development and the percentage of time infants were observed in various positions (being carried, lying down, sitting, crawling, standing or walking) and engaged in various activities (eating, sleeping, resting, crying/whining or playing) were compared by treatment group. No differences in motor development were observed by treatment group. However, at follow-up 2 (after 7 mo of supplementation), zinc-supplemented infants were significantly more frequently observed sitting up compared with lying down, and were playing during 4.18 +/- 1.95% (P < 0.05) more observations than unsupplemented infants. They were also somewhat less likely to be observed crying or whining (P < 0.10) compared with those receiving the placebo. These effects are independent of other factors including infant age, motor development, sex, maternal education, family socioeconomic status and nutritional status at base line. Further research must be conducted to determine the long-term developmental importance of these differences in activity patterns associated with zinc supplementation in this setting.

  6. Aversive Pavlovian Responses Affect Human Instrumental Motor Performance

    PubMed Central

    Rigoli, Francesco; Pavone, Enea Francesco; Pezzulo, Giovanni

    2012-01-01

    In neuroscience and psychology, an influential perspective distinguishes between two kinds of behavioral control: instrumental (habitual and goal-directed) and Pavlovian. Understanding the instrumental-Pavlovian interaction is fundamental for the comprehension of decision-making. Animal studies (as those using the negative auto-maintenance paradigm), have demonstrated that Pavlovian mechanisms can have maladaptive effects on instrumental performance. However, evidence for a similar effect in humans is scarce. In addition, the mechanisms modulating the impact of Pavlovian responses on instrumental performance are largely unknown, both in human and non-human animals. The present paper describes a behavioral experiment investigating the effects of Pavlovian conditioned responses on performance in humans, focusing on the aversive domain. Results showed that Pavlovian responses influenced human performance, and, similar to animal studies, could have maladaptive effects. In particular, Pavlovian responses either impaired or increased performance depending on modulator variables such as threat distance, task controllability, punishment history, amount of training, and explicit punishment expectancy. Overall, these findings help elucidating the computational mechanisms underlying the instrumental-Pavlovian interaction, which might be at the base of apparently irrational phenomena in economics, social behavior, and psychopathology. PMID:23060738

  7. Affective neuroscience of pleasure: reward in humans and animals

    PubMed Central

    2010-01-01

    Introduction Pleasure and reward are generated by brain circuits that are largely shared between humans and other animals. Discussion Here, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals. Conclusion Topics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness. PMID:18311558

  8. Salient sounds activate human visual cortex automatically

    PubMed Central

    McDonald, John J.; Störmer, Viola S.; Martinez, Antigona; Feng, Wenfeng; Hillyard, Steven A.

    2013-01-01

    Sudden changes in the acoustic environment enhance perceptual processing of subsequent visual stimuli that appear in close spatial proximity. Little is known, however, about the neural mechanisms by which salient sounds affect visual processing. In particular, it is unclear whether such sounds automatically activate visual cortex. To shed light on this issue, the present study examined event-related brain potentials (ERPs) that were triggered either by peripheral sounds that preceded task-relevant visual targets (Experiment 1) or were presented during purely auditory tasks (Experiments 2, 3, and 4). In all experiments the sounds elicited a contralateral ERP over the occipital scalp that was localized to neural generators in extrastriate visual cortex of the ventral occipital lobe. The amplitude of this cross-modal ERP was predictive of perceptual judgments about the contrast of co-localized visual targets. These findings demonstrate that sudden, intrusive sounds reflexively activate human visual cortex in a spatially specific manner, even during purely auditory tasks when the sounds are not relevant to the ongoing task. PMID:23699530

  9. Aggregatibacter actinomycetemcomitans lipopolysaccharide affects human gingival fibroblast cytoskeletal organization.

    PubMed

    Gutiérrez-Venegas, Gloria; Contreras-Marmolejo, Luis Arturo; Román-Alvárez, Patricia; Barajas-Torres, Carolina

    2008-04-01

    The cytoskeleton is a dynamic structure that plays a key role in maintaining cell morphology and function. This study investigates the effect of bacterial wall lipopolysaccharide (LPS), a strong inflammatory agent, on the dynamics and organization of actin, tubulin, vimentin, and vinculin proteins in human gingival fibroblasts (HGF). A time-dependent study showed a noticeable change in actin architecture after 1.5 h of incubation with LPS (1 microg/ml) with the formation of orthogonal fibers and further accumulation of actin filament at the cell periphery by 24 h. When 0.01-10 microg/ml of LPS was added to human gingival fibroblast cultures, cells acquired a round, flat shape and gradually developed cytoplasmic ruffling. Lipopolysaccharides extracted from Aggregatibacter actinomycetemcomitans periodontopathogenic bacteria promoted alterations in F-actin stress fibres of human gingival cells. Normally, human gingival cells have F-actin fibres that are organized in linear distribution throughout the cells, extending along the cell's length. LPS-treated cells exhibited changes in cytoskeletal protein organization, and F-actin was reorganized by the formation of bundles underneath and parallel to the cell membrane. We also found the reorganization of the vimentin network into vimentin bundling after 1.5 h of treatment. HGF cells exhibited diffuse and granular gamma-tubulin stain. There was no change in LPS-treated HGF. However, vinculin plaques distributed in the cell body diminished after LPS treatment. We conclude that the dynamic and structured organization of cytoskeletal filaments and actin assembly in human gingival fibroblasts is altered by LPS treatment and is accompanied by a decrease in F-actin pools.

  10. Human affection exchange: VI. Further tests of reproductive probability as a predictor of men's affection with their adult sons.

    PubMed

    Floyd, Kory; Sargent, Jack E; Di Corcia, Mark

    2004-04-01

    The authors examined the communication of affection in men's relationships with their fathers. Drawing from Affection Exchange Theory, the authors advanced four predictions: (a) heterosexual men receive more affection from their own fathers than do homosexual or bisexual men, (b) fathers communicate affection to their sons more through supportive activities than through direct verbal statements or nonverbal gestures, (c) affectionate communication between fathers and sons is linearly related to closeness and interpersonal involvement between them, and (d) fathers' awareness of their sons' sexual orientation is associated with the amount of affection that the fathers communicate to them. Participants were 170 adult men who completed questionnaires regarding affectionate communication in their relationships with their fathers. Half of the men were self-identified as exclusively heterosexual, and the other half were self-identified as exclusively homosexual or bisexual. The results supported all predictions substantially.

  11. A whole-genome RNA interference screen for human cell factors affecting myxoma virus replication.

    PubMed

    Teferi, Wondimagegnehu M; Dodd, Kristopher; Maranchuk, Rob; Favis, Nicole; Evans, David H

    2013-04-01

    Myxoma virus (MYXV) provides an important model for investigating host-pathogen interactions. Recent studies have also highlighted how mutations in transformed human cells can expand the host range of this rabbit virus. Although virus growth depends upon interactions between virus and host proteins, the nature of these interactions is poorly understood. To address this matter, we performed small interfering RNA (siRNA) screens for genes affecting MYXV growth in human MDA-MB-231 cells. By using siRNAs targeting the whole human genome (21,585 genes), a subset of human phosphatases and kinases (986 genes), and also a custom siRNA library targeting selected statistically significant genes ("hits") and nonsignificant genes ("nonhits") of the whole human genome screens (88 genes), we identified 711 siRNA pools that promoted MYXV growth and 333 that were inhibitory. Another 32 siRNA pools (mostly targeting the proteasome) were toxic. The overall overlap in the results was about 25% for the hits and 75% for the nonhits. These pro- and antiviral genes can be clustered into pathways and related groups, including well-established inflammatory and mitogen-activated protein kinase pathways, as well as clusters relating to β-catenin and the Wnt signaling cascade, the cell cycle, and cellular metabolism. The validity of a subset of these hits was independently confirmed. For example, treating cells with siRNAs that might stabilize cells in G(1), or inhibit passage into S phase, stimulated MYXV growth, and these effects were reproduced by trapping cells at the G(1)/S boundary with an inhibitor of cyclin-dependent kinases 4/6. By using 2-deoxy-D-glucose and plasmids carrying the gene for phosphofructokinase, we also confirmed that infection is favored by aerobic glycolytic metabolism. These studies provide insights into how the growth state and structure of cells affect MYXV growth and how these factors might be manipulated to advantage in oncolytic virus therapy.

  12. Inbreeding affects locomotor activity in Drosophila melanogaster at different ages.

    PubMed

    Manenti, Tommaso; Pertoldi, Cino; Moghadam, Neda Nasiri; Nasiri, Neda; Schou, Mads Fristrup; Kjærsgaard, Anders; Cavicchi, Sandro; Loeschcke, Volker

    2015-01-01

    The ability to move is essential for many behavioural traits closely related to fitness. Here we studied the effect of inbreeding on locomotor activity (LA) of Drosophila melanogaster at different ages under both dark and light regimes. We expected to find a decreased LA in inbred lines compared to control lines. We also predicted an increased differentiation between lines due to inbreeding. LA was higher in the dark compared to the light regime for both inbred and outbred control lines. As expected, inbreeding increased phenotypic variance in LA, with some inbred lines showing higher and some lower LA than control lines. Moreover, age per se did not affect LA neither in control nor in inbred lines, while we found a strong line by age interaction between inbred lines. Interestingly, inbreeding changed the daily activity pattern of the flies: these patterns were consistent across all control lines but were lost in some inbred lines. The departure in the daily pattern of LA in inbred lines may contribute to the inbreeding depression observed in inbred natural populations.

  13. Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes

    SciTech Connect

    Borella, P.; Giardino, A. )

    1991-08-01

    The effect of lead chloride and cadmium chloride on in vitro immunoglobulin (Ig) production by human lymphocytes was investigated. After 7 days in culture, lead added in the range of human exposure (207-1035 {mu}g/liter) significantly enhanced Ig production either when cells were activated by pokeweed mitogen (PWM) or not. The effect was dose-dependent and was related to the Pb were measured in the extracellular medium and in the cells. Independently of the mitogen addition, about 2% of the Pb added was accumulated in the cells, most being associated with the nuclear fraction. Those findings suggest that the Pb effects could depend on its uptake and distribution in the cells. Cadmium added in the 50-500 nM range exhibited a dose-independent mitogenic activity in unstimulated cells, whereas the Ig secretion was not significantly affected by Cd when cells were PWM-activated. A considerable intraindividual variability, however, was observed when blood donors were separately examined, with both an increase, a decrease, or no variation on Ig production. Furthermore, higher percentages of Cd were accumulated in the nuclear fraction, and lower in the cytosol and precipitate, in PWM-activated compared to resting lymphocytes. Genetic factors could be of importance for the observed variability of the immune response to cadmium, and the authors support the hypothesis that differences in the metallothionein (MT) inducibility could play a role.

  14. Multiscale factors affecting human attitudes toward snow leopards and wolves.

    PubMed

    Suryawanshi, Kulbhushansingh R; Bhatia, Saloni; Bhatnagar, Yash Veer; Redpath, Stephen; Mishra, Charudutt

    2014-12-01

    The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierarchically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at

  15. Disturbances of electrodynamic activity affect abortion in animals

    NASA Astrophysics Data System (ADS)

    Nedbalova, M.; Jandova, A.; Dohnalova, A.

    2011-12-01

    A specific kind of intracellular organelles, the mitochondria, is the place of metabolic energy production by oxidative mechanism. We used cell mediated immunity method for verification of the energy metabolism (ATP production). The antigen (immunological functional RNA) was obtained from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus (LDV) and prepared by the high pressure gel chromatography (HPGC). We have studied the immunological adaptability of LDH viral antigen in 62 pigs (12 parents and 50 piglings). Exitus of piglings was in case of positive imunological response on LDV. The statement results from a comparison of the relative frequency of an incidence of identical findings in male piglets and sows and from identical findings in female piglets and pigs. The efficient elaboration and utilization of energy in cell may be damaged by the changes of energy production systems and also by long-term parasitary depletion of ATP energy. Biological activity is based not only on biochemical but also on biophysical mechanisms. Biophysical processes are also involved in the transfer of information and its processing for making decisions and providing control, which are important parts of biological activity. These experimental results were used for the same study in human.

  16. Psychobiological Factors Affecting Cortisol Variability in Human-Dog Dyads

    PubMed Central

    Schöberl, Iris; Wedl, Manuela; Beetz, Andrea; Kotrschal, Kurt

    2017-01-01

    Stress responses within dyads are modulated by interactions such as mutual emotional support and conflict. We investigated dyadic psychobiological factors influencing intra-individual cortisol variability in response to different challenging situations by testing 132 owners and their dogs in a laboratory setting. Salivary cortisol was measured and questionnaires were used to assess owner and dog personality as well as owners' social attitudes towards the dog and towards other humans. We calculated the individual coefficient of variance of cortisol (iCV = sd/mean*100) over the different test situations as a parameter representing individual variability of cortisol concentration. We hypothesized that high cortisol variability indicates efficient and adaptive coping and a balanced individual and dyadic social performance. Female owners of male dogs had lower iCV than all other owner gender-dog sex combinations (F = 14.194, p<0.001), whereas owner Agreeableness (NEO-FFI) scaled positively with owner iCV (F = 4.981, p = 0.028). Dogs of owners high in Neuroticism (NEO-FFI) and of owners who were insecure-ambivalently attached to their dogs (FERT), had low iCV (F = 4.290, p = 0.041 and F = 5.948, p = 0.016), as had dogs of owners with human-directed separation anxiety (RSQ) or dogs of owners with a strong desire of independence (RSQ) (F = 7.661, p = 0.007 and F = 9.192, p = 0.003). We suggest that both owner and dog social characteristics influence dyadic cortisol variability, with the human partner being more influential than the dog. Our results support systemic approaches (i.e. considering the social context) in science and in counselling. PMID:28178272

  17. Skin blood perfusion and oxygenation colour affect perceived human health.

    PubMed

    Stephen, Ian D; Coetzee, Vinet; Law Smith, Miriam; Perrett, David I

    2009-01-01

    Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.

  18. Tech versus the Human Touch: Teacher Affect Is More Effective.

    ERIC Educational Resources Information Center

    Perry, Alan

    2003-01-01

    An experimental group studied Macbeth in an independent, constructivist setting using multimedia; the control group studied traditionally. Eleven of 23 experimental students and 2 of 21 in the traditional class failed. In an experiment with Hamlet, the results were reversed. Students were most successful when the teacher was actively involved,…

  19. Default, Cognitive, and Affective Brain Networks in Human Tinnitus

    DTIC Science & Technology

    2015-10-01

    Mapping (SPM8; a freely available fMRI analysis package), fMRI and structural imaging data from each session were aligned to a standard brain atlas...maps are superimposed on a mean of structural scans (average over subjects contributing to the activation maps). 3.3 Implication of results for the

  20. Sensing Human Activity: GPS Tracking

    PubMed Central

    van der Spek, Stefan; van Schaick, Jeroen; de Bois, Peter; de Haan, Remco

    2009-01-01

    The enhancement of GPS technology enables the use of GPS devices not only as navigation and orientation tools, but also as instruments used to capture travelled routes: as sensors that measure activity on a city scale or the regional scale. TU Delft developed a process and database architecture for collecting data on pedestrian movement in three European city centres, Norwich, Rouen and Koblenz, and in another experiment for collecting activity data of 13 families in Almere (The Netherlands) for one week. The question posed in this paper is: what is the value of GPS as ‘sensor technology’ measuring activities of people? The conclusion is that GPS offers a widely useable instrument to collect invaluable spatial-temporal data on different scales and in different settings adding new layers of knowledge to urban studies, but the use of GPS-technology and deployment of GPS-devices still offers significant challenges for future research. PMID:22574061

  1. Integrin activation controls metastasis in human breast cancer

    PubMed Central

    Felding-Habermann, Brunhilde; O'Toole, Timothy E.; Smith, Jeffrey W.; Fransvea, Emilia; Ruggeri, Zaverio M.; Ginsberg, Mark H.; Hughes, Paul E.; Pampori, Nisar; Shattil, Sanford J.; Saven, Alan; Mueller, Barbara M.

    2001-01-01

    Metastasis is the primary cause of death in human breast cancer. Metastasis to bone, lungs, liver, and brain involves dissemination of breast cancer cells via the bloodstream and requires adhesion within the vasculature. Blood cell adhesion within the vasculature depends on integrins, a family of transmembrane adhesion receptors, and is regulated by integrin activation. Here we show that integrin αvβ3 supports breast cancer cell attachment under blood flow conditions in an activation-dependent manner. Integrin αvβ3 was found in two distinct functional states in human breast cancer cells. The activated, but not the nonactivated, state supported tumor cell arrest during blood flow through interaction with platelets. Importantly, activated αvβ3 was expressed by freshly isolated metastatic human breast cancer cells and variants of the MDA-MB 435 human breast cancer cell line, derived from mammary fat pad tumors or distant metastases in severe combined immunodeficient mice. Expression of constitutively activated mutant αvβ3D723R, but not αvβ3WT, in MDA-MB 435 cells strongly promoted metastasis in the mouse model. Thus breast cancer cells can exhibit a platelet-interactive and metastatic phenotype that is controlled by the activation of integrin αvβ3. Consequently, alterations within tumors that lead to the aberrant control of integrin activation are expected to adversely affect the course of human breast cancer. PMID:11172040

  2. Integrin activation controls metastasis in human breast cancer

    NASA Astrophysics Data System (ADS)

    Felding-Habermann, Brunhilde; O'Toole, Timothy E.; Smith, Jeffrey W.; Fransvea, Emilia; Ruggeri, Zaverio M.; Ginsberg, Mark H.; Hughes, Paul E.; Pampori, Nisar; Shattil, Sanford J.; Saven, Alan; Mueller, Barbara M.

    2001-02-01

    Metastasis is the primary cause of death in human breast cancer. Metastasis to bone, lungs, liver, and brain involves dissemination of breast cancer cells via the bloodstream and requires adhesion within the vasculature. Blood cell adhesion within the vasculature depends on integrins, a family of transmembrane adhesion receptors, and is regulated by integrin activation. Here we show that integrin v3 supports breast cancer cell attachment under blood flow conditions in an activation-dependent manner. Integrin v3 was found in two distinct functional states in human breast cancer cells. The activated, but not the nonactivated, state supported tumor cell arrest during blood flow through interaction with platelets. Importantly, activated αvβ3 was expressed by freshly isolated metastatic human breast cancer cells and variants of the MDA-MB 435 human breast cancer cell line, derived from mammary fat pad tumors or distant metastases in severe combined immunodeficient mice. Expression of constitutively activated mutant αvβ3D723R, but not αvβ3WT, in MDA-MB 435 cells strongly promoted metastasis in the mouse model. Thus breast cancer cells can exhibit a platelet-interactive and metastatic phenotype that is controlled by the activation of integrin αvβ3. Consequently, alterations within tumors that lead to the aberrant control of integrin activation are expected to adversely affect the course of human breast cancer.

  3. International study of factors affecting human chromosome translocations

    PubMed Central

    Sigurdson, Alice J.; Ha, Mina; Hauptmann, Michael; Bhatti, Parveen; Sram, Radim J.; Beskid, Olena; Tawn, E. Janet; Whitehouse, Caroline A.; Lindholm, Carita; Nakano, Mimako; Kodama, Yoshiaki; Nakamura, Nori; Vorobtsova, Irena; Oestreicher, Ursula; Stephan, Günther; Yong, Lee C.; Bauchinger, Manfred; Schmid, Ernst; Chung, Hai Won; Darroudi, Firouz; Roy, Laurence; Voisin, Phillipe; Barquinero, Joan F.; Livingston, Gordon; Blakey, David; Hayata, Isamu; Zhang, Wei; Wang, Chunyan; Bennett, L. Michelle; Littlefield, L. Gayle; Edwards, Alan A.; Kleinerman, Ruth A.; Tucker, James D.

    2009-01-01

    Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from sixteen laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages vs. a linear relationship (p <0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09–1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes. PMID:18337160

  4. Relaxation training affects success and activation on a teaching test.

    PubMed

    Helin, P; Hänninen, O

    1987-12-01

    We studied the effects of an audiocassette-relaxation training period (ART) and its timing on success at a teaching test (lecture type), on observed tension and on a number of physiological responses. The electrical activity of the upper trapezius muscle (EMG), heart rate (HR) and blood pressure (BP), of female and male instructor candidates, were examined before, during and after the teaching test as well as during its critique. The relaxation period (18 min) was presented either on the preceding night (ARTnt) or immediately before the teaching test (ARTimm). The influence of personality (types A-B and extrovert-introvert) was also studied. ART improved success at the teaching test in both sexes. In males (but not in females), ARTimm decreased EMG level during the test, but ARTnt increased EMG at the test period as compared to the control group. In females, both ARTnt and ARTimm lowered HR more than in the control group. ARTimm lowered systolic BP in both sexes. Personality types affected the ART responses; ART was more beneficial for type A than B subjects.

  5. The impact of pre- and/or probiotics on human colonic metabolism: does it affect human health?

    PubMed

    De Preter, Vicky; Hamer, Henrike M; Windey, Karen; Verbeke, Kristin

    2011-01-01

    Since many years, the role of the colonic microbiota in maintaining the host's overall health and well-being has been recognized. Dietary modulation of the microbiota composition and activity has been achieved by the use of pre-, pro- and synbiotics. In this review, we will summarize the available evidence on the modification of bacterial metabolism by dietary intervention with pre-, pro- and synbiotics. Enhanced production of SCFA as a marker of increased saccharolytic fermentation is well documented in animal and in vitro studies. Decreased production of potentially toxic protein fermentation metabolites, such as sulfides, phenolic and indolic compounds, has been less frequently demonstrated. Besides, pre-, pro- and synbiotics also affect other metabolic pathways such as the deconjugation of secondary bile acids, bacterial enzyme activities and mineral absorption. Data from human studies are less conclusive. The emergence of new analytical techniques such as metabolite profiling has revealed new pathways affected by dietary intervention. However, an important challenge for current and future research is to relate changes in bacterial metabolism to concrete health benefits. Potential targets and expected benefits have been identified: reduced risk for the metabolic syndrome and prevention of colorectal cancer.

  6. The relationship between activating affects, inhibitory affects, and self-compassion in patients with Cluster C personality disorders.

    PubMed

    Schanche, Elisabeth; Stiles, Tore C; McCullough, Leigh; Svartberg, Martin; Nielsen, Geir Høstmark

    2011-09-01

    In the short-term dynamic psychotherapy model termed "Affect Phobia Treatment," it is assumed that increase in patients' defense recognition, decrease in inhibitory affects (e.g., anxiety, shame, guilt), and increase in the experience of activating affects (e.g., sadness, anger, closeness) are related to enhanced self-compassion across therapeutic approaches. The present study aimed to test this assumption on the basis of data from a randomized controlled trial, which compared a 40-session short-term dynamic psychotherapy (N = 25) with 40-session cognitive treatment (N = 25) for outpatients with Cluster C personality disorders. Patients' defense recognition, inhibitory affects, activating affects, and self-compassion were rated with the Achievement of Therapeutic Objectives Scale (McCullough et al., 2003b) in Sessions 6 and 36. Results showed that increase in self-compassion from early to late in therapy significantly predicted pre- to post-decrease in psychiatric symptoms, interpersonal problems, and personality pathology. Decrease in levels of inhibitory affects and increase in levels of activating affects during therapy were significantly associated with higher self-compassion toward the end of treatment. Increased levels of defense recognition did not predict higher self-compassion when changes in inhibitory and activating affects were statistically controlled for. There were no significant interaction effects with type of treatment. These findings support self-compassion as an important goal of psychotherapy and indicate that increase in the experience of activating affects and decrease in inhibitory affects seem to be worthwhile therapeutic targets when working to enhance self-compassion in patients with Cluster C personality disorders.

  7. Typha capensis (Rohrb.)N.E.Br. (bulrush) extract scavenges free radicals, inhibits collagenase activity and affects human sperm motility and mitochondrial membrane potential in vitro: a pilot study.

    PubMed

    Henkel, R; Fransman, W; Hipler, U-C; Wiegand, C; Schreiber, G; Menkveld, R; Weitz, F; Fisher, D

    2012-05-01

    The biodiversity in South Africa provides more than 30,000 higher plants, of which more than 3000 are used by traditional healers to treat diseases. Typha capensis (bulrush) is one of the medicinal plants used in South Africa to treat male fertility problems. Considering that South African traditional healers have been recognised by Law and the health benefits of T. capensis have not been scientifically investigated yet, this study aimed at investigating the in vitro effects of aqueous extracts from this plant on male reproductive functions. Both leaves and rhizomes of T. capensis were dried, infused with distilled water and freeze-dried. Motile sperm from 50 men were isolated by swim-up and incubated with 1 μg ml(-1) aqueous extract of Typha rhizome for 1 h at 37 °C. Vitality, motility, sperm production of reactive oxygen species and mitochondrial membrane potential were analysed in the test sample, a control and in the pellet from the swim-up. Results showed that the rhizome extract had significant (P < 0.0001) negative effects on all parameters. The extracts from the leaves and rhizomes revealed dose-dependent inhibitory activity for collagenase and free radical formation. No inhibitory activity for elastase was found. The inhibitory activity for collagenase might indicate possible anti-cancer effects.

  8. Noisy human neighbours affect where urban monkeys live

    PubMed Central

    Duarte, Marina H. L.; Vecci, Marco A.; Hirsch, André; Young, Robert J.

    2011-01-01

    Urban areas and many natural habitats are being dominated by a new selection pressure: anthropogenic noise. The ongoing expansion of urban areas, roads and airports throughout the world makes the noise almost omnipresent. Urbanization and the increase of noise levels form a major threat to living conditions in and around cities. Insight into the behavioural strategies of urban survivors may explain the sensitivity of other species to urban selection pressures. Here, we show that urban black-tufted marmosets (Callithrix penicillata) living in noisy urban areas may select their home-range based primarily on ambient noise level. We have tested the hypothesis that the noise from vehicular traffic and visitors in an urban park in Brazil influences the use of home-range (space) by urban marmosets. Marmosets even avoided noisy areas with high food availability. In addition, they systematically preferred the quieter areas even with dynamic changes in the acoustic landscape of the park between weekdays and Sundays (no observations were made on Saturdays). These data provide evidence that the use of home-range by wild animals can be affected by a potential aversive stimulus such as noise pollution. PMID:21715396

  9. Stress shifts brain activation towards ventral 'affective' areas during emotional distraction.

    PubMed

    Oei, Nicole Y L; Veer, Ilya M; Wolf, Oliver T; Spinhoven, Philip; Rombouts, Serge A R B; Elzinga, Bernet M

    2012-04-01

    Acute stress has been shown to impair working memory (WM), and to decrease prefrontal activation during WM in healthy humans. Stress also enhances amygdala responses towards emotional stimuli. Stress might thus be specifically detrimental to WM when one is distracted by emotional stimuli. Usually, emotional stimuli presented as distracters in a WM task slow down performance, while evoking more activation in ventral 'affective' brain areas, and a relative deactivation in dorsal 'executive' areas. We hypothesized that after acute social stress, this reciprocal dorsal-ventral pattern would be shifted towards greater increase of ventral 'affective' activation during emotional distraction, while impairing WM performance. To investigate this, 34 healthy men, randomly assigned to a social stress or control condition, performed a Sternberg WM task with emotional and neutral distracters inside an MRI scanner. Results showed that WM performance after stress tended to be slower during emotional distraction. Brain activations during emotional distraction was enhanced in ventral affective areas, while dorsal executive areas tended to show less deactivation after stress. These results suggest that acute stress shifts priority towards processing of emotionally significant stimuli, at the cost of WM performance.

  10. Neural coding of cooperative vs. affective human interactions: 150 ms to code the action's purpose.

    PubMed

    Proverbio, Alice Mado; Riva, Federica; Paganelli, Laura; Cappa, Stefano F; Canessa, Nicola; Perani, Daniela; Zani, Alberto

    2011-01-01

    The timing and neural processing of the understanding of social interactions was investigated by presenting scenes in which 2 people performed cooperative or affective actions. While the role of the human mirror neuron system (MNS) in understanding actions and intentions is widely accepted, little is known about the time course within which these aspects of visual information are automatically extracted. Event-Related Potentials were recorded in 35 university students perceiving 260 pictures of cooperative (e.g., 2 people dragging a box) or affective (e.g., 2 people smiling and holding hands) interactions. The action's goal was automatically discriminated at about 150-170 ms, as reflected by occipito/temporal N170 response. The swLORETA inverse solution revealed the strongest sources in the right posterior cingulate cortex (CC) for affective actions and in the right pSTS for cooperative actions. It was found a right hemispheric asymmetry that involved the fusiform gyrus (BA37), the posterior CC, and the medial frontal gyrus (BA10/11) for the processing of affective interactions, particularly in the 155-175 ms time window. In a later time window (200-250 ms) the processing of cooperative interactions activated the left post-central gyrus (BA3), the left parahippocampal gyrus, the left superior frontal gyrus (BA10), as well as the right premotor cortex (BA6). Women showed a greater response discriminative of the action's goal compared to men at P300 and anterior negativity level (220-500 ms). These findings might be related to a greater responsiveness of the female vs. male MNS. In addition, the discriminative effect was bilateral in women and was smaller and left-sided in men. Evidence was provided that perceptually similar social interactions are discriminated on the basis of the agents' intentions quite early in neural processing, differentially activating regions devoted to face/body/action coding, the limbic system and the MNS.

  11. Default, Cognitive, and Affective Brain Networks in Human Tinnitus

    DTIC Science & Technology

    2014-10-01

    fMRI session 1 in which subjects perform a working memory task (“2-Back”) and a simple detection task (“Detect 1’s”) based on (a) visual and (b...two major brain networks: the cognitive control network (CCN) and the default mode network (DMN). Using fMRI , we are examining brain activation in...subjects performing cognitive tasks that engage the CCN and DMN. One task is heavily reliant on working memory (N-back) and the other on selective

  12. Factors affecting distribution of airflow in a human tracheobronchial cast.

    PubMed

    Cohen, B S; Sussman, R G; Lippmann, M

    1993-09-01

    Air velocity was measured at end airways of hollow replicate casts of the human tracheobronchial tree in order to determine the flow distribution within casts extending to 3 mm diameter airways. Measurements were made by hot-wire anemometry for constant inspiratory flow rates of 7.5, 15, 30 and 60 L.min-1. Average flow distribution among the lung lobes was as follows: right upper, 18.5%; right middle, 9.2%; right lower, 32.3%; left upper, 15.7%; and left lower, 24.3%. An empirical model derived from the experimental flow distribution data demonstrated the effect of various morphometric parameters of the hollow cast on the distribution of airflow. Airway cross-sectional area, branching angle and total path-length were found to have the greatest influence. As the tracheal flow rate decreased from 60 to 7.5 L.min-1, the influence of branching angle was reduced, while total path-length became more influential. These results provide evidence for the transition of flow regimes within the TB tree within normal physiological flow ranges.

  13. Mimicry profiles are affected by human-induced habitat changes.

    PubMed

    Azmeh, S; Owen, J; Sørensen, K; Grewcock, D; Gilbert, F

    1998-12-07

    Mimicry theory predicts that mimics in a Batesian mimicry complex evolve to resemble models closely, and that there is a limit on the numbers of mimics relative to models. For hoverflies (Diptera: Syrphidae), supposed mimics of social wasps (Hymenoptera: Vespidae, neither of these is true; many mimics are imperfect and in the UK and Europe they outnumber their models manifold. We hypothesized that the high abundance of mimics relative to models in the UK may be the result not just of mimic model dynamics, but of habitat changes caused by humans. Most of the larvae of poor mimics are aphidophagous, and changes from ancient forest to agricultural and/or urban habitats may have vastly augmented aphid numbers. Using new and literature data, we compared mimicry profiles of habitats differing in their degree of habitat disturbance. In both cases more highly disturbed habitats had proportionally more poor mimics and fewer high-fidelity mimics than less disturbed habitats. This supports the hypothesis that habitat change has an effect on model to mimic ratios.

  14. Family poverty affects the rate of human infant brain growth.

    PubMed

    Hanson, Jamie L; Hair, Nicole; Shen, Dinggang G; Shi, Feng; Gilmore, John H; Wolfe, Barbara L; Pollak, Seth D

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

  15. Family Poverty Affects the Rate of Human Infant Brain Growth

    PubMed Central

    Hanson, Jamie L.; Hair, Nicole; Shen, Dinggang G.; Shi, Feng; Gilmore, John H.; Wolfe, Barbara L.; Pollak, Seth D.

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  16. What experimental experience affects dogs' comprehension of human communicative actions?

    PubMed

    Hauser, Marc D; Comins, Jordan A; Pytka, Lisa M; Cahill, Donal P; Velez-Calderon, Sofia

    2011-01-01

    Studies of dogs report that individuals reliably respond to the goal-directed communicative actions (e.g., pointing) of human experimenters. All of these studies use some version of a multi-trial approach, thereby allowing for the possibility of rapid learning within an experimental session. The experiments reported here ask whether dogs can respond correctly to a communicative action based on only a single presentation, thereby eliminating the possibility of learning within the experimental context. We tested 173 dogs. For each dog reaching our test criteria, we used a single presentation of six different goal-directed actions within a session, asking whether they correctly follow to a target goal (container with concealed food) a (1) distal hand point, (2) step toward one container, (3) hand point to one container followed by step toward the other, (4) step toward one container and point to the other, (5) distal foot point with the experimenter's hands free, and (6) distal foot point with the experimenter's hands occupied. Given only a single presentation, dogs selected the correct container when the experimenter hand pointed, foot pointed with hands occupied, or stepped closer to the target container, but failed on the other actions, despite using the same method. The fact that dogs correctly followed foot pointing with hands occupied, but not hands free, suggests that they are sensitive to environmental constraints, and use this information to infer rational, goal-directed action. We discuss these results in light of the role of experience in recognizing communicative gestures, as well as the significance of coding criteria for studies of canine competence.

  17. Human Islets Exhibit Electrical Activity on Microelectrode Arrays (MEA).

    PubMed

    Schönecker, S; Kraushaar, U; Guenther, E; Gerst, F; Ullrich, S; Häring, H-U; Königsrainer, A; Barthlen, W; Drews, G; Krippeit-Drews, P

    2015-05-01

    This study demonstrates for the first time that the microelectrode array (MEA) technique allows analysis of electrical activity of islets isolated from human biopsies. We have shown before that this method, i.e., measuring beta cell electrical activity with extracellular electrodes, is a powerful tool to assess glucose responsiveness of isolated murine islets. In the present study, human islets were shown to exhibit glucose-dependent oscillatory electrical activity. The glucose responsiveness could be furthermore demonstrated by an increase of insulin secretion in response to glucose. Electrical activity was increased by tolbutamide and inhibited by diazoxide. In human islets bursts of electrical activity were markedly blunted by the Na(+) channel inhibitor tetrodotoxin which does not affect electrical activity in mouse islets. Thus, the MEA technique emerges as a powerful tool to decipher online the unique features of human islets.Additionally, this technique will enable research with human islets even if only a few islets are available and it will allow a fast and easy test of metabolic integrity of islets destined for transplantation.

  18. Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

    PubMed

    Tamarozzi, F; Wright, H L; Johnston, K L; Edwards, S W; Turner, J D; Taylor, M J

    2014-10-01

    The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism.

  19. Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

    PubMed Central

    Martinez, Zachary S.; Castro, Edison; Seong, Chang-Soo; Cerón, Maira R.

    2016-01-01

    Three compounds (1, 2, and 3) previously reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase were studied, but only fullerene derivatives 1 and 2 showed strong antiviral activity on the replication of HIV-1 in human CD4+ T cells. However, these compounds did not inhibit infection by single-round infection vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped viruses, indicating no effect on the early steps of the viral life cycle. In contrast, analysis of single-round infection VSV-G-pseudotyped HIV-1 produced in the presence of compound 1 or 2 showed a complete lack of infectivity in human CD4+ T cells, suggesting that the late stages of the HIV-1 life cycle were affected. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. However, Gag and Gag-Pol processing was affected, as evidenced by immunoblot analysis with an anti-p24 antibody and the measurement of virion-associated reverse transcriptase activity, ratifying the effect of the fullerene derivatives on virion maturation of the HIV-1 life cycle. Surprisingly, fullerenes 1 and 2 did not inhibit HIV-1 protease in an in vitro assay at the doses that potently blocked viral infectivity, suggesting a protease-independent mechanism of action. Highlighting the potential therapeutic relevance of fullerene derivatives, these compounds block infection by HIV-1 resistant to protease and maturation inhibitors. PMID:27431232

  20. Environmental noise levels affect the activity budget of the Florida manatee

    NASA Astrophysics Data System (ADS)

    Miksis-Olds, Jennifer L.; Donaghay, Percy L.; Miller, James H.; Tyack, Peter L.

    2005-09-01

    Manatees inhabit coastal bays, lagoons, and estuaries because they are dependent on the aquatic vegetation that grows in shallow waters. Food requirements force manatees to occupy the same areas in which human activities are the greatest. Noise produced from human activities has the potential to affect these animals by eliciting responses ranging from mild behavioral changes to extreme aversion. This study quantifies the behavioral responses of manatees to both changing levels of ambient noise and transient noise sources. Results indicate that elevated environmental noise levels do affect the overall activity budget of this species. The proportion of time manatees spend feeding, milling, and traveling in critical habitats changed as a function of noise level. More time was spent in the directed, goal-oriented behaviors of feeding and traveling, while less time was spent milling when noise levels were highest. The animals also responded to the transient noise of approaching vessels with changes in behavioral state and movements out of the geographical area. This suggests that manatees detect and respond to changes in environmental noise levels. Whether these changes legally constitute harassment and produce biologically significant effects need to be addressed with hypothesis-driven experiments and long-term monitoring. [For Animal Bioacoustics Best Student Paper Award.

  1. Foetal bovine serum-derived exosomes affect yield and phenotype of human cardiac progenitor cell culture

    PubMed Central

    Angelini, Francesco; Ionta, Vittoria; Rossi, Fabrizio; Miraldi, Fabio; Messina, Elisa; Giacomello, Alessandro

    2016-01-01

    Introduction: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation. Methods: The aim of this study was to analyse, from a qualitative and quantitative point of view, the in vitro effects of bovine serum exosomes on human CPCs cultured either as cardiospheres or as monolayers of cardiosphere-forming cells. Results: Effects on proliferation, yield and molecular patterning were detected. We show, for the first time, that exogenous bovine exosomes support the proliferation and migration of human cardiosphere-forming cells, and that their depletion affects cardiospheres formation, in terms of size, yield and extra-cellular matrix production. Conclusion: These results stress the importance of considering differential biological effects of exogenous cell culture supplements on the final phenotype of primary human cell cultures. PMID:27340620

  2. Does human pressure affect the community structure of surf zone fish in sandy beaches?

    NASA Astrophysics Data System (ADS)

    Costa, Leonardo Lopes; Landmann, Júlia G.; Gaelzer, Luiz R.; Zalmon, Ilana R.

    2017-01-01

    Intense tourism and human activities have resulted in habitat destruction in sandy beach ecosystems with negative impacts on the associated communities. To investigate whether urbanized beaches affect surf zone fish communities, fish and their benthic macrofaunal prey were collected during periods of low and high human pressure at two beaches on the Southeastern Brazilian coast. A BACI experimental design (Before-After-Control-Impact) was adapted for comparisons of tourism impact on fish community composition and structure in urbanized, intermediate and non-urbanized sectors of each beach. At the end of the summer season, we observed a significant reduction in fish richness, abundance, and diversity in the high tourist pressure areas. The negative association between visitors' abundance and the macrofaunal density suggests that urbanized beaches are avoided by surf zone fish due to higher human pressure and the reduction of food availability. Our results indicate that surf zone fish should be included in environmental impact studies in sandy beaches, including commercial species, e.g., the bluefish Pomatomus saltatrix. The comparative results from the less urbanized areas suggest that environmental zoning and visitation limits should be used as effective management and preservation strategies on beaches with high conservation potential.

  3. Beta2-adrenergic signaling affects the phenotype of human cardiac progenitor cells through EMT modulation.

    PubMed

    Pagano, Francesca; Angelini, Francesco; Siciliano, Camilla; Tasciotti, Julia; Mangino, Giorgio; De Falco, Elena; Carnevale, Roberto; Sciarretta, Sebastiano; Frati, Giacomo; Chimenti, Isotta

    2017-01-15

    Human cardiac progenitor cells (CPCs) offer great promises to cardiac cell therapy for heart failure. Many in vivo studies have shown their therapeutic benefits, paving the way for clinical translation. The 3D model of cardiospheres (CSs) represents a unique niche-like in vitro microenvironment, which includes CPCs and supporting cells. CSs have been shown to form through a process mediated by epithelial-to-mesenchymal transition (EMT). β2-Adrenergic signaling significantly affects stem/progenitor cells activation and mobilization in multiple tissues, and crosstalk between β2-adrenergic signaling and EMT processes has been reported. In the present study, we aimed at investigating the biological response of CSs to β2-adrenergic stimuli, focusing on EMT modulation in the 3D culture system of CSs. We treated human CSs and CS-derived cells (CDCs) with the β2-blocker butoxamine (BUT), using either untreated or β2 agonist (clenbuterol) treated CDCs as control. BUT-treated CS-forming cells displayed increased migration capacity and a significant increase in their CS-forming ability, consistently associated with increased expression of EMT-related genes, such as Snai1. Moreover, long-term BUT-treated CDCs contained a lower percentage of CD90+ cells, and this feature has been previously correlated with higher cardiogenic and therapeutic potential of the CDCs population. In addition, long-term BUT-treated CDCs had an increased ratio of collagen-III/collagen-I gene expression levels, and showed decreased release of inflammatory cytokines, overall supporting a less fibrosis-prone phenotype. In conclusion, β2 adrenergic receptor block positively affected the stemness vs commitment balance within CSs through the modulation of type1-EMT (so called "developmental"). These results further highlight type-1 EMT to be a key process affecting the features of resident cardiac progenitor cells, and mediating their response to the microenvironment.

  4. Age‐related neuromuscular changes affecting human vastus lateralis

    PubMed Central

    Piasecki, M.; Ireland, A.; Stashuk, D.; Hamilton‐Wright, A.; Jones, D. A.

    2015-01-01

    Key points Skeletal muscle size and strength decline in older age.The vastus lateralis, a large thigh muscle, undergoes extensive neuromuscular remodelling in healthy ageing, as characterized by a loss of motor neurons, enlargement of surviving motor units and instability of neuromuscular junction transmission.The loss of motor axons and changes to motor unit potential transmission precede a clinically‐relevant loss of muscle mass and function. Abstract The anterior thigh muscles are particularly susceptible to muscle loss and weakness during ageing, although how this is associated with changes to neuromuscular structure and function in terms of motor unit (MU) number, size and MU potential (MUP) stability remains unclear. Intramuscular (I.M.) and surface electromyographic signals were recorded from the vastus lateralis (VL) during voluntary contractions held at 25% maximal knee extensor strength in 22 young (mean ± SD, 25.3 ± 4.8 years) and 20 physically active older men (71.4 ± 6.2 years). MUP size, firing rates, phases, turns and near fibre (NF) jiggle were determined and MU number estimates (MUNEs) were made by comparing average surface MUP with maximal electrically‐evoked compound muscle action potentials. Quadriceps cross‐sectional area was measured by magnetic resonance imaging. In total, 379 individual MUs were sampled in younger men and 346 in older men. Compared to the MU in younger participants, those in older participants had 8% lower firing rates and larger MUP size (+25%), as well as increased complexity, as indicated by phases (+13%), turns (+20%) and NF jiggle (+11%) (all P < 0.0005). The MUNE values (derived from the area of muscle in range of the surface‐electrode) in older participants were ∼70% of those in the young (P < 0.05). Taking into consideration the 30% smaller cross‐sectional area of the VL, the total number of MUs in the older muscles was between 50% and 60% lower compared to in young muscles (P < 0

  5. Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides.

    PubMed

    Yi, Guanghui; Brendel, Volker P; Shu, Chang; Li, Pingwei; Palanathan, Satheesh; Cheng Kao, C

    2013-01-01

    The STING (stimulator of interferon genes) protein can bind cyclic dinucleotides to activate the production of type I interferons and inflammatory cytokines. The cyclic dinucleotides can be bacterial second messengers c-di-GMP and c-di-AMP, 3'5'-3'5' cyclic GMP-AMP (3'3' cGAMP) produced by Vibrio cholerae and metazoan second messenger 2'5'-3'5' Cyclic GMP-AMP (2'3' cGAMP). Analysis of single nucleotide polymorphism (SNP) data from the 1000 Genome Project revealed that R71H-G230A-R293Q (HAQ) occurs in 20.4%, R232H in 13.7%, G230A-R293Q (AQ) in 5.2%, and R293Q in 1.5% of human population. In the absence of exogenous ligands, the R232H, R293Q and AQ SNPs had only modest effect on the stimulation of IFN-β and NF-κB promoter activities in HEK293T cells, while HAQ had significantly lower intrinsic activity. The decrease was primarily due to the R71H substitution. The SNPs also affected the response to the cyclic dinucleotides. In the presence of c-di-GMP, the R232H variant partially decreased the ability to activate IFN-βsignaling, while it was defective for the response to c-di-AMP and 3'3' cGAMP. The R293Q dramatically decreased the stimulatory response to all bacterial ligands. Surprisingly, the AQ and HAQ variants maintained partial abilities to activate the IFN-β signaling in the presence of ligands due primarily to the G230A substitution. Biochemical analysis revealed that the recombinant G230A protein could affect the conformation of the C-terminal domain of STING and the binding to c-di-GMP. Comparison of G230A structure with that of WT revealed that the conformation of the lid region that clamps onto the c-di-GMP was significantly altered. These results suggest that hSTING variation can affect innate immune signaling and that the common HAQ haplotype expresses a STING protein with reduced intrinsic signaling activity but retained the ability to response to bacterial cyclic dinucleotides.

  6. Does the trematode Centrocestus formosanus affect the locomotory activity of the mollusc Melanoides tuberculatus?

    PubMed Central

    2013-01-01

    Background Melanoides tuberculatus (Müller, 1774) (Thiaridae), an introduced gastropod mollusc with a wide geographical distribution in the Neotropics, is the intermediate host of the trematode Centrocestus formosanus (Nishigori, 1924) (Heterophyidae). This parasite is considered to be pathogenic to humans. The aim of the present work was to evaluate the locomotory activity of uninfected M. tuberculatus compared with those naturally infected with C. formosanus. Findings The locomotory activity of each mollusc was recorded using an image analysis biomonitoring system, Videomex-V ®, to evaluate and quantify the parameters of ‘Stereotypic’ and ‘Resting time’. The Generalized Estimating Equation analysis of locomotory activity of M. tuberculatus infected with C. formosanus revealed significant differences compared with uninfected molluscs for the parameters ‘Stereotypic time’ and ‘Resting time’ with a reduction of movement. The variations in the values of the monitoring intervals recorded showed a significant difference for the infected molluscs in the case of Stereotypic time, with an irregular locomotory activity pattern, as compared to that of uninfected molluscs. The analysis of the standard length of all molluscs did not exhibit any correlation with locomotory activity, showing that C. formosanus is able to alter the locomotory activity of its snail host regardless of the standard length. Conclusions The trematode C. formosanus affects the locomotory activity of the mollusc M. tuberculatus by reducing its movement and causing it to exhibit an irregular pattern of activity, both of which are independent of the snail's standard length. PMID:23574763

  7. Activation of human lymphocytes by supernatants from human thymic epithelium.

    PubMed

    Goust, J M; Vesole, D H; Fudenberg, H H

    1979-11-01

    Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS.

  8. Activation of human lymphocytes by supernatants from human thymic epithelium.

    PubMed Central

    Goust, J M; Vesole, D H; Fudenberg, H H

    1979-01-01

    Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS. PMID:160851

  9. Levodopa influences striatal activity but does not affect cortical hyper-activity in Parkinson's disease.

    PubMed

    Martinu, K; Degroot, C; Madjar, C; Strafella, A P; Monchi, O

    2012-02-01

    Motor studies of Parkinson's disease (PD) have shown cortical hypo-activity in relation to nigrostriatal dopamine depletion. Cognitive studies also identified increased cortical activity in PD. We have previously suggested that the hypo-activity/hyper-activity patterns observed in PD are related to the striatal contribution. Tasks that recruit the striatum in control participants are associated with cortical hypo-activity in patients with PD, whereas tasks that do not result in cortical hyper-activity. The putamen, a structure affected by the neurodegeneration observed in PD, shows increased activation for externally-triggered (ET) and self-initiated (SI) movements. The first goal of this study was to evaluate the effect of levodopa on the putamen's response to ET and SI movements. Our second goal was to assess the effect of levodopa on the hypo-activity/hyper-activity patterns in cortical areas. Patients with PD on and off levodopa and healthy volunteers performed SI, ET and control finger movements during functional magnetic resonance imaging. Healthy participants displayed significant differences in putamen activity in ET and SI movements. These differences were reduced in patients off medication, with non-task-specific increases in activity after levodopa administration. Furthermore, the ventrolateral prefrontal cortex showed significant increases in activity during SI movements in healthy controls, whereas it was hypo-active in PD. This region showed significantly increased activity during ET movements in patients off medication. Levodopa had no effect on this discrepancy. Our results suggest that dopamine replacement therapy has a non-task-specific effect on motor corticostriatal regions, and support the hypothesis that increases and decreases in cortical activity in PD are related to the mesocortical dopamine pathway imbalance.

  10. Physical environment virtualization for human activities recognition

    NASA Astrophysics Data System (ADS)

    Poshtkar, Azin; Elangovan, Vinayak; Shirkhodaie, Amir; Chan, Alex; Hu, Shuowen

    2015-05-01

    Human activity recognition research relies heavily on extensive datasets to verify and validate performance of activity recognition algorithms. However, obtaining real datasets are expensive and highly time consuming. A physics-based virtual simulation can accelerate the development of context based human activity recognition algorithms and techniques by generating relevant training and testing videos simulating diverse operational scenarios. In this paper, we discuss in detail the requisite capabilities of a virtual environment to aid as a test bed for evaluating and enhancing activity recognition algorithms. To demonstrate the numerous advantages of virtual environment development, a newly developed virtual environment simulation modeling (VESM) environment is presented here to generate calibrated multisource imagery datasets suitable for development and testing of recognition algorithms for context-based human activities. The VESM environment serves as a versatile test bed to generate a vast amount of realistic data for training and testing of sensor processing algorithms. To demonstrate the effectiveness of VESM environment, we present various simulated scenarios and processed results to infer proper semantic annotations from the high fidelity imagery data for human-vehicle activity recognition under different operational contexts.

  11. Understanding human dynamics in microblog posting activities

    NASA Astrophysics Data System (ADS)

    Jiang, Zhihong; Zhang, Yubao; Wang, Hui; Li, Pei

    2013-02-01

    Human activity patterns are an important issue in behavior dynamics research. Empirical evidence indicates that human activity patterns can be characterized by a heavy-tailed inter-event time distribution. However, most researchers give an understanding by only modeling the power-law feature of the inter-event time distribution, and those overlooked non-power-law features are likely to be nontrivial. In this work, we propose a behavior dynamics model, called the finite memory model, in which humans adaptively change their activity rates based on a finite memory of recent activities, which is driven by inherent individual interest. Theoretical analysis shows a finite memory model can properly explain various heavy-tailed inter-event time distributions, including a regular power law and some non-power-law deviations. To validate the model, we carry out an empirical study based on microblogging activity from thousands of microbloggers in the Celebrity Hall of the Sina microblog. The results show further that the model is reasonably effective. We conclude that finite memory is an effective dynamics element to describe the heavy-tailed human activity pattern.

  12. Deep Human Parsing with Active Template Regression.

    PubMed

    Liang, Xiaodan; Liu, Si; Shen, Xiaohui; Yang, Jianchao; Liu, Luoqi; Dong, Jian; Lin, Liang; Yan, Shuicheng

    2015-12-01

    In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28].

  13. A Whole-Genome RNA Interference Screen for Human Cell Factors Affecting Myxoma Virus Replication

    PubMed Central

    Teferi, Wondimagegnehu M.; Dodd, Kristopher; Maranchuk, Rob; Favis, Nicole

    2013-01-01

    Myxoma virus (MYXV) provides an important model for investigating host-pathogen interactions. Recent studies have also highlighted how mutations in transformed human cells can expand the host range of this rabbit virus. Although virus growth depends upon interactions between virus and host proteins, the nature of these interactions is poorly understood. To address this matter, we performed small interfering RNA (siRNA) screens for genes affecting MYXV growth in human MDA-MB-231 cells. By using siRNAs targeting the whole human genome (21,585 genes), a subset of human phosphatases and kinases (986 genes), and also a custom siRNA library targeting selected statistically significant genes (“hits”) and nonsignificant genes (“nonhits”) of the whole human genome screens (88 genes), we identified 711 siRNA pools that promoted MYXV growth and 333 that were inhibitory. Another 32 siRNA pools (mostly targeting the proteasome) were toxic. The overall overlap in the results was about 25% for the hits and 75% for the nonhits. These pro- and antiviral genes can be clustered into pathways and related groups, including well-established inflammatory and mitogen-activated protein kinase pathways, as well as clusters relating to β-catenin and the Wnt signaling cascade, the cell cycle, and cellular metabolism. The validity of a subset of these hits was independently confirmed. For example, treating cells with siRNAs that might stabilize cells in G1, or inhibit passage into S phase, stimulated MYXV growth, and these effects were reproduced by trapping cells at the G1/S boundary with an inhibitor of cyclin-dependent kinases 4/6. By using 2-deoxy-d-glucose and plasmids carrying the gene for phosphofructokinase, we also confirmed that infection is favored by aerobic glycolytic metabolism. These studies provide insights into how the growth state and structure of cells affect MYXV growth and how these factors might be manipulated to advantage in oncolytic virus therapy. PMID

  14. Detection of cardiac activity changes from human speech

    NASA Astrophysics Data System (ADS)

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

    2015-05-01

    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  15. Real-World Affected Upper Limb Activity in Chronic Stroke: An Examination of Potential Modifying Factors

    PubMed Central

    Bailey, Ryan R.; Birkenmeier, Rebecca L.; Lang, Catherine E.

    2015-01-01

    BACKGROUND Despite improvement in motor function after intervention, adults with chronic stroke experience disability in everyday activity. Factors other than motor function may influence affected upper limb (UL) activity. OBJECTIVE To characterize affected UL activity and examine potential modifying factors of affected UL activity in community-dwelling adults with chronic stroke. METHODS Forty-six adults with chronic stroke wore accelerometers on both ULs for 25 hours and provided information about potential modifying factors (time spent in sedentary activity, cognitive impairment, depressive symptomatology, number of comorbidities, motor dysfunction of the affected UL, age, activities of daily living (ADL) status, and living arrangement). Accelerometry was used to quantify duration of affected and unaffected UL activity. The ratio of affected-to-unaffected UL activity was also calculated. Associations within and between accelerometry-derived variables and potential modifying factors were examined. RESULTS Mean hours of affected and unaffected UL activity were 5.0 ± 2.2 and 7.6 ± 2.1 hours, respectively. The ratio of affected-to-unaffected UL activity was 0.64 ± 0.19, and hours of affected and unaffected UL activity were strongly correlated (r=0.78). Increased severity of motor dysfunction and dependence in ADLs were associated with decreased affected UL activity. No other factors were associated with affected UL activity. CONCLUSIONS Severity of motor dysfunction and ADL status should be taken into consideration when setting goals for UL activity in people with chronic stroke. Given the strong, positive correlation between affected and unaffected UL activity, encouragement to increase activity of the unaffected UL may increase affected UL activity. PMID:25776118

  16. Recognition of Intensive Valence and Arousal Affective States via Facial Electromyographic Activity in Young and Senior Adults

    PubMed Central

    Li, Hang; Walter, Steffen; Hrabal, David; Rukavina, Stefanie; Limbrecht-Ecklundt, Kerstin; Hoffman, Holger; Traue, Harald C.

    2016-01-01

    Background Research suggests that interaction between humans and digital environments characterizes a form of companionship in addition to technical convenience. To this effect, humans have attempted to design computer systems able to demonstrably empathize with the human affective experience. Facial electromyography (EMG) is one such technique enabling machines to access to human affective states. Numerous studies have investigated the effects of valence emotions on facial EMG activity captured over the corrugator supercilii (frowning muscle) and zygomaticus major (smiling muscle). The arousal emotion, specifically, has not received much research attention, however. In the present study, we sought to identify intensive valence and arousal affective states via facial EMG activity. Methods Ten blocks of affective pictures were separated into five categories: neutral valence/low arousal (0VLA), positive valence/high arousal (PVHA), negative valence/high arousal (NVHA), positive valence/low arousal (PVLA), and negative valence/low arousal (NVLA), and the ability of each to elicit corresponding valence and arousal affective states was investigated at length. One hundred and thirteen participants were subjected to these stimuli and provided facial EMG. A set of 16 features based on the amplitude, frequency, predictability, and variability of signals was defined and classified using a support vector machine (SVM). Results We observed highly accurate classification rates based on the combined corrugator and zygomaticus EMG, ranging from 75.69% to 100.00% for the baseline and five affective states (0VLA, PVHA, PVLA, NVHA, and NVLA) in all individuals. There were significant differences in classification rate accuracy between senior and young adults, but there was no significant difference between female and male participants. Conclusion Our research provides robust evidences for recognition of intensive valence and arousal affective states in young and senior adults. These

  17. Dynamic changes in brain activations and functional connectivity during affectively different tactile stimuli.

    PubMed

    Hua, Qing-Ping; Zeng, Xiang-Zhu; Liu, Jian-Yu; Wang, Jin-Yan; Guo, Jian-You; Luo, Fei

    2008-01-01

    In the present study, we compared brain activations produced by pleasant, neutral and unpleasant touch, to the anterior lateral surface of lower leg of human subjects. It was found that several brain regions, including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), as well as contralateral middle and posterior insula cortex were commonly activated under the three touch conditions. In addition, pleasant and unpleasant touch conditions shared a few brain regions including the contralateral posterior parietal cortex (PPC) and bilateral premotor cortex (PMC). Unpleasant touch specifically activated a set of pain-related brain regions such as contralateral supplementary motor area (SMA) and dorsal parts of bilateral anterior cingulated cortex, etc. Brain regions specifically activated by pleasant touch comprised bilateral lateral orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), intraparietal cortex and left dorsal lateral prefrontal cortex (DLPFC). Using a novel functional connectivity model based on graph theory, we showed that a series of brain regions related to affectively different touch had significant functional connectivity during the resting state. Furthermore, it was found that such a network can be modulated between affectively different touch conditions.

  18. Human telomerase: biogenesis, trafficking, recruitment, and activation.

    PubMed

    Schmidt, Jens C; Cech, Thomas R

    2015-06-01

    Telomerase is the ribonucleoprotein enzyme that catalyzes the extension of telomeric DNA in eukaryotes. Recent work has begun to reveal key aspects of the assembly of the human telomerase complex, its intracellular trafficking involving Cajal bodies, and its recruitment to telomeres. Once telomerase has been recruited to the telomere, it appears to undergo a separate activation step, which may include an increase in its repeat addition processivity. This review covers human telomerase biogenesis, trafficking, and activation, comparing key aspects with the analogous events in other species.

  19. Human telomerase: biogenesis, trafficking, recruitment, and activation

    PubMed Central

    Schmidt, Jens C.

    2015-01-01

    Telomerase is the ribonucleoprotein enzyme that catalyzes the extension of telomeric DNA in eukaryotes. Recent work has begun to reveal key aspects of the assembly of the human telomerase complex, its intracellular trafficking involving Cajal bodies, and its recruitment to telomeres. Once telomerase has been recruited to the telomere, it appears to undergo a separate activation step, which may include an increase in its repeat addition processivity. This review covers human telomerase biogenesis, trafficking, and activation, comparing key aspects with the analogous events in other species. PMID:26063571

  20. Antioxidant activity of olive polyphenols in humans: a review.

    PubMed

    Raederstorff, Daniel

    2009-05-01

    In vitro and animal studies show that polyphenols from olives have potent antioxidant activities; 50 % of the phenolic compounds contained in olives and virgin olive oil are hydroxytyrosol and derivatives thereof. Hydroxytyrosol is the major olive polyphenol consumed and well absorbed in humans. It is considered to have the highest antioxidant potency compared to the other olive polyphenols. Review of the human intervention studies showed that olive polyphenols decreased the levels of oxidized-LDL in plasma and positively affected several biomarkers of oxidative damage. The antioxidant effects of olive polyphenols on low-density lipoprotein (LDL) oxidation are observed after a dietary intake of about 10 mg per day. The overall evidence from in vitro assays, and animal and human studies support the antioxidant effect of olive polyphenols. However, further larger human studies are needed to clarify the effect of olive polyphenols on markers of oxidative stress, particularly DNA damage and plasma isoprostane levels.

  1. Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele.

    PubMed

    Anders, Silke; Sack, Benjamin; Pohl, Anna; Münte, Thomas; Pramstaller, Peter; Klein, Christine; Binkofski, Ferdinand

    2012-04-01

    Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia-cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia-cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons ('mirror neurons') in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia-cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in

  2. Balancing protein stability and activity in cancer: a new approach for identifying driver mutations affecting CBL ubiquitin ligase activation

    PubMed Central

    Li, Minghui; Kales, Stephen C.; Ma, Ke; Shoemaker, Benjamin A.; Crespo-Barreto, Juan; Cangelosi, Andrew L.; Lipkowitz, Stanley; Panchenko, Anna R.

    2015-01-01

    Oncogenic mutations in the monomeric Casitas B-lineage lymphoma (Cbl) gene have been found in many tumors, but their significance remains largely unknown. Several human c-Cbl (CBL) structures have recently been solved depicting the protein at different stages of its activation cycle and thus provide mechanistic insight underlying how stability-activity tradeoffs in cancer-related proteins may influence disease onset and progression. In this study, we computationally modeled the effects of missense cancer mutations on structures representing four stages of the CBL activation cycle to identify driver mutations that affect CBL stability, binding, and activity. We found that recurrent, homozygous, and leukemia-specific mutations had greater destabilizing effects on CBL states than did random non-cancer mutations. We further tested the ability of these computational models assessing the changes in CBL stability and its binding to ubiquitin conjugating enzyme E2, by performing blind CBL-mediated EGFR ubiquitination assays in cells. Experimental CBL ubiquitin ligase activity was in agreement with the predicted changes in CBL stability and, to a lesser extent, with CBL-E2 binding affinity. Two-thirds of all experimentally tested mutations affected the ubiquitin ligase activity by either destabilizing CBL or disrupting CBL-E2 binding, whereas about one-third of tested mutations were found to be neutral. Collectively, our findings demonstrate that computational methods incorporating multiple protein conformations and stability and binding affinity evaluations can successfully predict the functional consequences of cancer mutations on protein activity, and provide a proof of concept for mutations in CBL. PMID:26676746

  3. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States.

    PubMed

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-03-21

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects' affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain's motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states.

  4. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States

    NASA Astrophysics Data System (ADS)

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-03-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects’ affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain’s motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states.

  5. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States

    PubMed Central

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-01-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects’ affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain’s motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states. PMID:26996254

  6. [The effect of goal framing on the activation of affective representations].

    PubMed

    Takehashi, Hiroki; Karasawa, Kaori

    2007-10-01

    Guided by regulatory focus theory, this study examined the effects of goal framing on the subjective experience of affect and the accessibility of affective representations. Study I examined lay persons' beliefs concerning the relationship between goal framing and certain kinds of affective experiences. The results indicated that a promotion focus was associated with happiness and disappointment, whereas a prevention focus was associated with relaxation and tension. Study 2 examined the effect of goal framing on the activation of affective representations, and found that a promotion focus activated both gain-related representations (happy and disappointment) and loss-related representations (relaxation and tension), whereas a prevention focus activated only loss-related representations. These results suggest that goal framing activates particular affective representations, and the activated affective representations may influence the interpretation of positive or negative experiences. The discussion considered the function of the activation of affective representations as a mediator between goal framing and its cognitive and behavioral consequences.

  7. T Cell Activation Thresholds are Affected by Gravitational

    NASA Technical Reports Server (NTRS)

    Adams, Charley; Gonzalez, M.; Nelman-Gonzalez, M.

    1999-01-01

    T cells stimulated in space flight by various mitogenic signals show a dramatic reduction in proliferation and expression of early activation markers. Similar results are also obtained in a ground based model of microgravity, clinorotation, which provides a vector-averaged reduction of the apparent gravity on cells without significant shear force. Here we demonstrate that T cell inhibition is due to an increase in the required threshold for activation. Dose response curves indicate that cells activated during clinorotation require higher stimulation to achieve the same level of activation, as measured by CD69 expression. Interleukin 2 receptor expression, and DNA synthesis. The amount of stimulation necessary for 50% activation is 5 fold in the clinostat relative to static. Correlation of TCR internalization with activation also exhibit a dramatic right shift in clinorotation, demonstrating unequivocally that signal transduction mechanism independent of TCR triggering account for the increased activation threshold. Previous results from space flight experiments are consistent with the dose response curves obtained for clinorotation. Activation thresholds are important aspects of T cell memory, autoimmunity and tolerance Clinorotation is a useful, noninvasive tool for the study of cellular and biochemical event regulating T cell activation threshold and the effects of gravitation forces on these systems.

  8. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    NASA Astrophysics Data System (ADS)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (sbnd NH2), carboxyl (sbnd COOH) and methyl (sbnd CH3), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (sbnd COOH and sbnd NH2) can absorb more proteins than these modified with more hydrophobic functional group (sbnd CH3). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the sbnd NH2 modified surfaces encourage osteogenic differentiation; the sbnd COOH modified surfaces promote cell adhesion and spreading and the sbnd CH3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  9. Interacting Physical and Biological Processes Affecting Nutrient Transport Through Human Dominated Landscapes

    NASA Astrophysics Data System (ADS)

    Finlay, J. C.

    2015-12-01

    Human activities increasingly dominate biogeochemical cycles of limiting nutrients on Earth. Urban and agricultural landscapes represent the largest sources of excess nutrients that drive water quality degradation. The physical structure of both urban and agricultural watersheds has been extensively modified, and these changes have large impacts on water and nutrient transport. Despite strong physical controls over nutrient transport in human dominated landscapes, biological processes play important roles in determining the fates of both nitrogen and phosphorus. This talk uses examples from research in urban and agricultural watersheds in the Midwestern USA to illustrate interactions of physical and biological controls over nutrient cycles that have shifted nitrogen (N) and phosphorus (P) sources and cycling in unexpected ways in response to management changes. In urban watersheds, efforts to improve water quality have been hindered by legacy sources of phosphorus added to storm water through transport to drainage systems by vegetation. Similarly, reductions in field erosion in agricultural watersheds have not led to major reductions in phosphorus transport, because of continued release of biological sources of P. Where management of phosphorus has been most effective in reducing eutrophication of lakes, decreases in N removal processes have led to long term increases in N concentration and transport. Together, these examples show important roles for biological processes affecting nutrient movement in highly modified landscapes. Consideration of the downstream physical and biological responses of management changes are thus critical toward identification of actions that will most effectively reduce excess nutrients watersheds and coastal zones.

  10. Expansion of adipose mesenchymal stromal cells is affected by human platelet lysate and plating density.

    PubMed

    Cholewa, Dominik; Stiehl, Thomas; Schellenberg, Anne; Bokermann, Gudrun; Joussen, Sylvia; Koch, Carmen; Walenda, Thomas; Pallua, Norbert; Marciniak-Czochra, Anna; Suschek, Christoph V; Wagner, Wolfgang

    2011-01-01

    The composition of mesenchymal stromal cells (MSCs) changes in the course of in vitro culture expansion. Little is known how these cell preparations are influenced by culture media, plating density, or passaging. In this study, we have isolated MSCs from human adipose tissue in culture medium supplemented with either fetal calf serum (FCS) or human platelet lysate (HPL). In addition, culture expansion was simultaneously performed at plating densities of 10 or 10,000 cells/cm(2). The use of FCS resulted in larger cells, whereas HPL significantly enhanced proliferation. Notably, HPL also facilitated expansion for more population doublings than FCS (43 ± 3 vs. 22 ± 4 population doubling; p < 0.001), while plating density did not have a significant effect on long-term growth curves. To gain further insight into population dynamics, we conceived a cellular automaton model to simulate expansion of MSCS. It is based on the assumptions that the number of cell divisions is limited and that due to contact inhibition proliferation occurs only at the rim of colonies. The model predicts that low plating densities result in more heterogeneity with regard to cell division history, and favor subpopulations of higher migratory activity. In summary, HPL is a suitable serum supplement for isolation of MSC from adipose tissue and facilitates more population doublings than FCS. Cellular automaton computer simulations provided additional insights into how complex population dynamics during long-term expansion are affected by plating density and migration.

  11. A recent evolutionary change affects a regulatory element in the human FOXP2 gene.

    PubMed

    Maricic, Tomislav; Günther, Viola; Georgiev, Oleg; Gehre, Sabine; Curlin, Marija; Schreiweis, Christiane; Naumann, Ronald; Burbano, Hernán A; Meyer, Matthias; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Gajovic, Srecko; Kelso, Janet; Enard, Wolfgang; Schaffner, Walter; Pääbo, Svante

    2013-04-01

    The FOXP2 gene is required for normal development of speech and language. By isolating and sequencing FOXP2 genomic DNA fragments from a 49,000-year-old Iberian Neandertal and 50 present-day humans, we have identified substitutions in the gene shared by all or nearly all present-day humans but absent or polymorphic in Neandertals. One such substitution is localized in intron 8 and affects a binding site for the transcription factor POU3F2, which is highly conserved among vertebrates. We find that the derived allele of this site is less efficient than the ancestral allele in activating transcription from a reporter construct. The derived allele also binds less POU3F2 dimers than POU3F2 monomers compared with the ancestral allele. Because the substitution in the POU3F2 binding site is likely to alter the regulation of FOXP2 expression, and because it is localized in a region of the gene associated with a previously described signal of positive selection, it is a plausible candidate for having caused a recent selective sweep in the FOXP2 gene.

  12. Human DJ-1-specific Transcriptional Activation of Tyrosine Hydroxylase Gene*

    PubMed Central

    Ishikawa, Shizuma; Taira, Takahiro; Takahashi-Niki, Kazuko; Niki, Takeshi; Ariga, Hiroyoshi; Iguchi-Ariga, Sanae M. M.

    2010-01-01

    Loss-of-function mutation in the DJ-1 gene causes a subset of familial Parkinson disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. DJ-1 has multiple functions, including transcriptional regulation, and one of transcriptional target genes for DJ-1 is the tyrosine hydroxylase (TH) gene, the product of which is a key enzyme for dopamine biosynthesis. It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. In this study, we found that knockdown of human DJ-1 by small interference RNA in human dopaminergic cell lines attenuated TH gene expression and 4-dihydroxy-l-phenylalanine production but that knockdown or knock-out of mouse DJ-1 in mouse cell lines or in mice did not affect such expression and TH activity. In reporter assays using the human TH gene promoter linked to the luciferase gene, stimulation of TH promoter activity was observed in human cells, but not mouse cells, that had been transfected with DJ-1. Although human DJ-1 and mouse DJ-1 were associated either with human or with mouse PSF, TH promoter activity inhibited by PSF was restored by human DJ-1 but not by mouse DJ-1. Chromatin immunoprecipitation assays revealed that the complex of PSF with DJ-1 bound to the human but not the mouse TH gene promoter. These results suggest a novel species-specific transcriptional regulation of the TH promoter by DJ-1 and one of the mechanisms for no reduction of TH in DJ-1-knock-out mice. PMID:20938049

  13. Human DJ-1-specific transcriptional activation of tyrosine hydroxylase gene.

    PubMed

    Ishikawa, Shizuma; Taira, Takahiro; Takahashi-Niki, Kazuko; Niki, Takeshi; Ariga, Hiroyoshi; Iguchi-Ariga, Sanae M M

    2010-12-17

    Loss-of-function mutation in the DJ-1 gene causes a subset of familial Parkinson disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. DJ-1 has multiple functions, including transcriptional regulation, and one of transcriptional target genes for DJ-1 is the tyrosine hydroxylase (TH) gene, the product of which is a key enzyme for dopamine biosynthesis. It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. In this study, we found that knockdown of human DJ-1 by small interference RNA in human dopaminergic cell lines attenuated TH gene expression and 4-dihydroxy-L-phenylalanine production but that knockdown or knock-out of mouse DJ-1 in mouse cell lines or in mice did not affect such expression and TH activity. In reporter assays using the human TH gene promoter linked to the luciferase gene, stimulation of TH promoter activity was observed in human cells, but not mouse cells, that had been transfected with DJ-1. Although human DJ-1 and mouse DJ-1 were associated either with human or with mouse PSF, TH promoter activity inhibited by PSF was restored by human DJ-1 but not by mouse DJ-1. Chromatin immunoprecipitation assays revealed that the complex of PSF with DJ-1 bound to the human but not the mouse TH gene promoter. These results suggest a novel species-specific transcriptional regulation of the TH promoter by DJ-1 and one of the mechanisms for no reduction of TH in DJ-1-knock-out mice.

  14. Scaling behavior of online human activity

    NASA Astrophysics Data System (ADS)

    Zhao, Zhi-Dan; Cai, Shi-Min; Huang, Junming; Fu, Yan; Zhou, Tao

    2012-11-01

    The rapid development of the Internet technology enables humans to explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e., traces), we can get insights about the dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, books, and movies rating, are comprehensively investigated by using the detrended fluctuation analysis technique and the multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three types of media show similar scaling properties with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based on their activities (i.e., rating per unit time), we find that the scaling exponents of the interevent time series in the three groups are different. Hence, these results suggest that a stronger long-range correlations exist in these collective behaviors. Furthermore, their information complexities vary in the three groups. To explain the differences of the collective behaviors restricted to the three groups, we study the dynamic behavior of human activity at the individual level, and find that the dynamic behaviors of a few users have extremely small scaling exponents associated with long-range anticorrelations. By comparing the interevent time distributions of four representative users, we can find that the bimodal distributions may bring forth the extraordinary scaling behaviors. These results of the analysis of the online human activity in the e-commerce may not only provide insight into its dynamic behaviors but may also be applied to acquire potential economic interest.

  15. 76 FR 65734 - Guidance for Industry on Evaluating the Safety of Flood-Affected Food Crops for Human Consumption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-24

    ...-Affected Food Crops for Human Consumption; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled ``Guidance for Industry: Evaluating the Safety of Flood-Affected Food Crops for Human Consumption... information on how to evaluate the safety of flood-affected food crops for human consumption. DATES:...

  16. Active tectonics and human survival strategies

    NASA Astrophysics Data System (ADS)

    King, Geoffrey; Bailey, Geoffrey; Sturdy, Derek

    1994-10-01

    Tectonic movements continuously remould the surface of Earth in response to plate motion. Yet such deformation is rarely taken into account when assessing landscape change and its impact on human land use, except perhaps as an occasional hazard to human life or a temporary disruption in the longer term patterns of human history. However, active tectonics also create and sustain landscapes that can be beneficial to human survival, forming a complex topography of potentially fertile sedimentary basins enclosed by mountain barriers that can facilitate the control and explotation of food resources, especially animal prey. We discuss the tectonic history of northwest Greece and show how the Paleolithic sites of the region are located to take advantage of tectonically created features at both a local and a regional scale. We suggest that the association of significant concentrations of early Paleolithic sites with tectonically acitve regions is not coincidental and that on the longer time spans of human biological evolution, active tectonics has been an important selective agent contributing to the development of the human species as an intelligent predator.

  17. Facets of dynamic positive affect: differentiating joy, interest, and activation in the positive and negative affect schedule (PANAS).

    PubMed

    Egloff, Boris; Schmukle, Stefan C; Burns, Lawrence R; Kohlmann, Carl-Walter; Hock, Michael

    2003-09-01

    This article proposes the differentiation of Joy, Interest, and Activation in the Positive Affect (PA) scale of the Positive and Negative Affect Schedule (PANAS; D. Watson, L. A. Clark, & A. Tellegen, 1988). Study 1 analyzed the dynamic course of PA before, during, and after an exam and established the differentiation of the three facets. Study 2 used a multistate-multitrait analysis to confirm this structure. Studies 3-5 used success-failure experiences, speaking tasks, and feedback of exam results to further examine PA facets in affect-arousing settings. All studies provide convincing evidence for the benefit of differentiating three facets of PA in the PANAS: Joy, Interest, and Activation do have distinct and sometimes even opposite courses that make their separation meaningful and rewarding.

  18. On universality in human correspondence activity.

    PubMed

    Malmgren, R Dean; Stouffer, Daniel B; Campanharo, Andriana S L O; Amaral, Luís A Nunes

    2009-09-25

    The identification and modeling of patterns of human activity have important ramifications for applications ranging from predicting disease spread to optimizing resource allocation. Because of its relevance and availability, written correspondence provides a powerful proxy for studying human activity. One school of thought is that human correspondence is driven by responses to received correspondence, a view that requires a distinct response mechanism to explain e-mail and letter correspondence observations. We demonstrate that, like e-mail correspondence, the letter correspondence patterns of 16 writers, performers, politicians, and scientists are well described by the circadian cycle, task repetition, and changing communication needs. We confirm the universality of these mechanisms by rescaling letter and e-mail correspondence statistics to reveal their underlying similarity.

  19. MEASURING CHOLINESTERASE ACTIVITY IN HUMAN SALIVA

    EPA Science Inventory

    To assess the potential for using saliva in pesticide biomonitoring, the consistency of cholinesterase activity in human saliva collected over time was examined. In this pilot study, saliva was collected from 20 healthy adults once per week for 5 consecutive weeks using 2 differe...

  20. The Human Activity of Evaluation Theorizing.

    ERIC Educational Resources Information Center

    Alkin, Marvin C.; Ellett, Frederick, Jr.

    Theorizing about evaluation should be conceptualized as a human activity governed by certain strategies and principles. The theories advanced by various evaluators have changed over the years, thus illustrating ten principles of evaluation. The starting point for theory development or modification is self-reflection and review of one's own…

  1. MEASURING CHOLINESTERASE ACTIVITY IN HUMAN SALIVA.

    EPA Science Inventory

    To assess the potential for using saliva in pesticide biomonitoring, the consistency of cholinesterase activity in human saliva collected over time was examined. In this pilot study, saliva was collected from 20 healthy adults once per week for 5 consecutive weeks using 2 differe...

  2. Food & Fitness. Directory. Human Nutrition Activities.

    ERIC Educational Resources Information Center

    Department of Agriculture, Washington, DC.

    Activities of the following regulatory and food service agencies of the Department of Agriculture are described: (1) Agricultural Research Service; (2) Cooperative State Research Service; (3) Economic Research Service; (4) Human Nutrition Information Service; (5) Office of Grants and Program Systems; (6) Office of International Cooperation and…

  3. Scaling laws of human interaction activity.

    PubMed

    Rybski, Diego; Buldyrev, Sergey V; Havlin, Shlomo; Liljeros, Fredrik; Makse, Hernán A

    2009-08-04

    Even though people in our contemporary technological society are depending on communication, our understanding of the underlying laws of human communicational behavior continues to be poorly understood. Here we investigate the communication patterns in 2 social Internet communities in search of statistical laws in human interaction activity. This research reveals that human communication networks dynamically follow scaling laws that may also explain the observed trends in economic growth. Specifically, we identify a generalized version of Gibrat's law of social activity expressed as a scaling law between the fluctuations in the number of messages sent by members and their level of activity. Gibrat's law has been essential in understanding economic growth patterns, yet without an underlying general principle for its origin. We attribute this scaling law to long-term correlation patterns in human activity, which surprisingly span from days to the entire period of the available data of more than 1 year. Further, we provide a mathematical framework that relates the generalized version of Gibrat's law to the long-term correlated dynamics, which suggests that the same underlying mechanism could be the source of Gibrat's law in economics, ranging from large firms, research and development expenditures, gross domestic product of countries, to city population growth. These findings are also of importance for designing communication networks and for the understanding of the dynamics of social systems in which communication plays a role, such as economic markets and political systems.

  4. Physical Activity Affects Brain Integrity in HIV + Individuals

    PubMed Central

    Ortega, Mario; Baker, Laurie M.; Vaida, Florin; Paul, Robert; Basco, Brian; Ances, Beau M.

    2015-01-01

    Prior research has suggested benefits of aerobic physical activity (PA) on cognition and brain volumes in HIV uninfected (HIV−) individuals, however, few studies have explored the relationships between PA and brain integrity (cognition and structural brain volumes) in HIV-infected (HIV +) individuals. Seventy HIV + individuals underwent neuropsychological testing, structural neuroimaging, laboratory tests, and completed a PA questionnaire, recalling participation in walking, running, and jogging activities over the last year. A PA engagement score of weekly metabolic equivalent (MET) hr of activity was calculated using a compendium of PAs. HIV + individuals were classified as physically active (any energy expended above resting expenditure, n = 22) or sedentary (n = 48). Comparisons of neuropsychological performance, grouped by executive and motor domains, and brain volumes were completed between groups. Physically active and sedentary HIV + individuals had similar demographic and laboratory values, but the active group had higher education (14.0 vs. 12.6 years, p = .034). Physically active HIV + individuals performed better on executive (p = .040, unadjusted; p = .043, adjusted) but not motor function (p = .17). In addition, among the physically active group the amount of physical activity (METs) positively correlated with executive (Pearson’s r = 0.45, p = 0.035) but not motor (r = 0.21; p = .35) performance. In adjusted analyses the physically active HIV + individuals had larger putamen volumes (p = .019). A positive relationship exists between PA and brain integrity in HIV + individuals. Results from the present study emphasize the importance to conduct longitudinal interventional investigation to determine if PA improves brain integrity in HIV + individuals. PMID:26581799

  5. Quiescence does not affect p53 and stress response by irradiation in human lung fibroblasts

    SciTech Connect

    Dai, Jiawen; Itahana, Koji; Baskar, Rajamanickam

    2015-02-27

    Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G{sub 1}/S or G{sub 2}/M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G{sub 0}, therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10–1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration. - Highlights: • p53 response by irradiation was similar between proliferating and quiescent cells. • Quiescent cells showed similar profiles of cell cycle proteins after irradiation. • Radioprotection of GSK-3β inhibitor caused similar effects between these cells. • Quiescence did not affect p53 response despite its

  6. 75 FR 62634 - Proposed Information Collection (Obligation to Report Factors Affecting Entitlement) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... AFFAIRS Proposed Information Collection (Obligation to Report Factors Affecting Entitlement) Activity... techniques or the use of other forms of information technology. Title: Obligation to Report Factors Affecting... entitlement factors. Individual factors such as income, marital status, and the beneficiary's number...

  7. 78 FR 46418 - Proposed Information Collection (Obligation To Report Factors Affecting Entitlement) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... AFFAIRS Proposed Information Collection (Obligation To Report Factors Affecting Entitlement) Activity... techniques or the use of other forms of information technology. Title: Obligation to Report Factors Affecting... entitlement factors. Individual factors such as income, marital status, and the beneficiary's number...

  8. Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

    PubMed

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

    2015-09-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections.

  9. Olanzapine and aripiprazole differentially affect glucose uptake and energy metabolism in human mononuclear blood cells.

    PubMed

    Stapel, Britta; Kotsiari, Alexandra; Scherr, Michaela; Hilfiker-Kleiner, Denise; Bleich, Stefan; Frieling, Helge; Kahl, Kai G

    2017-05-01

    The use of antipsychotics carries the risk of metabolic side effects, such as weight gain and new onset type-2 diabetes mellitus. The mechanisms of the observed metabolic alterations are not fully understood. We compared the effects of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (aripiprazole), on glucose metabolism. Primary human peripheral blood mononuclear cells (PBMC) were isolated and stimulated with olanzapine or aripiprazole for 72 h. Cellular glucose uptake was analyzed in vitro by 18F-FDG uptake. Further measurements comprised mRNA expression of glucose transporter (GLUT) 1 and 3, GLUT1 protein expression, DNA methylation of GLUT1 promoter region, and proteins involved in downstream glucometabolic processes. We observed a 2-fold increase in glucose uptake after stimulation with aripiprazole. In contrast, olanzapine stimulation decreased glucose uptake by 40%, accompanied by downregulation of the cellular energy sensor AMP activated protein kinase (AMPK). GLUT1 protein expression increased, GLUT1 mRNA expression decreased, and GLUT1 promoter was hypermethylated with both antipsychotics. Pyruvat-dehydrogenase (PDH) complex activity decreased with olanzapine only. Our findings suggest that the atypical antipsychotics olanzapine and aripiprazole differentially affect energy metabolism in PBMC. The observed decrease in glucose uptake in olanzapine stimulated PBMC, accompanied by decreased PDH point to a worsening in cellular energy metabolism not compensated by AMKP upregulation. In contrast, aripiprazole stimulation lead to increased glucose uptake, while not affecting PDH complex expression. The observed differences may be involved in the different metabolic profiles observed in aripiprazole and olanzapine treated patients.

  10. Luminal acetylcholine does not affect the activity of the CFTR in tracheal epithelia of pigs.

    PubMed

    Dittrich, Nikolaus P; Kummer, Wolfgang; Clauss, Wolfgang G; Fronius, Martin

    2015-11-01

    Fluid homeostasis mediated by the airway epithelium is required for proper lung function, and the CFTR (cystic fibrosis transmembrane conductance regulator) Cl(-) channel is crucial for these processes. Luminal acetylcholine (ACh) acts as an auto-/paracrine mediator to activate Cl(-) channels in airway epithelia and evidence exists showing that nicotinic ACh receptors activate CFTR in murine airway epithelia. The present study investigated whether or not luminal ACh regulates CFTR activity in airway epithelia of pigs, an emerging model for investigations of human airway disease and cystic fibrosis (CF) in particular. Transepithelial ion currents of freshly dissected pig tracheal preparations were measured with Ussing chambers. Application of luminal ACh (100 μM) induced an increase of the short-circuit current (I(SC)). The ACh effect was mimicked by muscarine and pilocarpine (100 μM each) and was sensitive to muscarinic receptor antagonists (atropine, 4-DAMP, pirenzepine). No changes of the I(SC) were observed by nicotine (100 μM) and ACh responses were not affected by nicotine or mecamylamine (25 μM). Luminal application of IBMX (I, 100 μM) and forskolin (F, 10 μM), increase the I(SC) and the I/F-induced current were decreased by the CFTR inhibitor GlyH-101 (GlyH, 50 μM) indicating increased CFTR activity by I/F. In contrast, GlyH did not affect the ACh-induced current, indicating that the ACh response does not involve the activation of the CFTR. Results from this study suggest that luminal ACh does not regulate the activity of the CFTR in tracheal epithelia of pigs which opposes observation from studies using mice airway epithelium.

  11. Oxidative Activity of Heated Coal Affected by Antypirogens

    NASA Astrophysics Data System (ADS)

    Torosyan, V. F.; Torosyan, E. S.; Borovikov, I. F.; Yakutova, V. A.

    2016-04-01

    The effect of antypirogens on chemical activity of heated coal is studied. It is proved that ammonium sulfate, calcium phosphate, calcium chloride, calcium nitrate and acid fluoride are the most effective antypirogens.

  12. Factors affecting antibacterial activity of hop compounds and their derivatives.

    PubMed

    Simpson, W J; Smith, A R

    1992-04-01

    The antibacterial effect of weak acids derived from the hop plant (Humulus lupulus L.) increased with decreasing pH. Analysis of the minimum inhibitory concentration of such compounds against Lactobacillus brevis IFO 3960 over pH 4-7 suggests that undissociated molecules were mainly responsible for inhibition of bacterial growth. The antibacterial activity of trans-isohumulone was ca 20 times greater than that of humulone, 11 times greater than that of colupulone and nine times greater than that of trans-humulinic acid when the degree of ionization was taken into account. Monovalent cations (K+, Na+, NH4+, Rb+, Li+) stimulated antibacterial activity of trans-isohumulone but the effect was smaller than that observed with H+. The response to divalent cations varied: Ca2+ had little effect on antibacterial activity, whereas Mg2+ reduced activity. Lipid materials and beta-cyclodextrin also antagonized the antibacterial action of trans-isohumulone.

  13. Technology trends, energy prices affect worldwide rig activity

    SciTech Connect

    Rappold, K.

    1995-09-25

    The major worldwide offshore rig markets have improved slightly this year, while the onshore markets generally lagged slightly. Offshore rig utilization rates have remained strong worldwide, with some areas reaching nearly 100%. Total worldwide offshore rig (jack ups, semisubmersible, drillships, submersibles, and barges) utilization was about 86%. Offshore drilling activity is driven primarily by oil and natural gas price expectations. Natural gas prices tend to drive North American offshore drilling activity, including the shallow waters in the Gulf of Mexico. International offshore drilling activity and deepwater projects in the Gulf of Mexico are more closely tied to oil prices. The paper discusses US rig count, directional drilling activity, jack up rig demand, semisubmersibles demand, rig replacement costs, and new construction.

  14. Habitat degradation affects the summer activity of polar bears.

    PubMed

    Ware, Jasmine V; Rode, Karyn D; Bromaghin, Jeffrey F; Douglas, David C; Wilson, Ryan R; Regehr, Eric V; Amstrup, Steven C; Durner, George M; Pagano, Anthony M; Olson, Jay; Robbins, Charles T; Jansen, Heiko T

    2017-02-28

    Understanding behavioral responses of species to environmental change is critical to forecasting population-level effects. Although climate change is significantly impacting species' distributions, few studies have examined associated changes in behavior. Polar bear (Ursus maritimus) subpopulations have varied in their near-term responses to sea ice decline. We examined behavioral responses of two adjacent subpopulations to changes in habitat availability during the annual sea ice minimum using activity data. Location and activity sensor data collected from 1989 to 2014 for 202 adult female polar bears in the Southern Beaufort Sea (SB) and Chukchi Sea (CS) subpopulations were used to compare activity in three habitat types varying in prey availability: (1) land; (2) ice over shallow, biologically productive waters; and (3) ice over deeper, less productive waters. Bears varied activity across and within habitats with the highest activity at 50-75% sea ice concentration over shallow waters. On land, SB bears exhibited variable but relatively high activity associated with the use of subsistence-harvested bowhead whale carcasses, whereas CS bears exhibited low activity consistent with minimal feeding. Both subpopulations had fewer observations in their preferred shallow-water sea ice habitats in recent years, corresponding with declines in availability of this substrate. The substantially higher use of marginal habitats by SB bears is an additional mechanism potentially explaining why this subpopulation has experienced negative effects of sea ice loss compared to the still-productive CS subpopulation. Variability in activity among, and within, habitats suggests that bears alter their behavior in response to habitat conditions, presumably in an attempt to balance prey availability with energy costs.

  15. Bronchorelaxation of the human bronchi by CFTR activators.

    PubMed

    Norez, Caroline; Jayle, Christophe; Becq, Frédéric; Vandebrouck, Clarisse

    2014-02-01

    The airway functions are profoundly affected in many diseases including asthma, COPD and cystic fibrosis (CF). CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR (Cystic Fibrosis transmembrane Conductance Regulator) gene, which normally encodes a multifunctional and integral membrane cAMP regulated and ATP gated Cl(-) channel expressed in airway epithelial cells. Using human lung tissues obtained from patients undergoing surgery for lung cancer, we demonstrated that CFTR participates in bronchorelaxation. Using human bronchial smooth muscle cells (HBSMC), we applied iodide influx assay to analyze the CFTR-dependent ionic transport and immunofluorescence technique to localize CFTR proteins. Moreover, the relaxation was studied in isolated human bronchial segments after pre-contraction with carbachol to determine the implication of CFTR in bronchodilation. We found in HBSMC that the pharmacology and regulation of CFTR is similar to that of its epithelial counterpart both for activation (using forskolin/genistein or a benzo[c]quinolizinium derivative) and for inhibition (CFTR(inh)-172 and GPinh5a). With human bronchial rings, we observed that whatever the compound used including salbutamol, the activation of muscular CFTR leads to a bronchodilation after constriction with carbachol. Altogether, these observations revealed that CFTR in the human airways is expressed in bronchial smooth muscle cells and can be pharmacologically manipulated leading to the hypothesis that this ionic channel could contribute to bronchodilation in human.

  16. The impacts of local human activities on the Antarctic environment

    NASA Astrophysics Data System (ADS)

    Tin, T.; Fleming, Z. L.; Hughes, K. A.; Ainley, D. G.; Convey, P.; Moreno, C. A.; Pfeiffer, S.; Scott, J.; Snape, I.

    2009-04-01

    An overview of a recently published review of the scientific literature from the past decade on the impacts of human activities on the Antarctic environment is presented. An assessment of the cumulative effects of scientists and accompanying base construction, tourists and fishery activities in Antarctica is timely given a decade since the Protocol on Environmental Protection to the Antarctic Treaty came into force in 1998 and the increasing attention given to and human presence in Antarctica during this 2007-2009 IPY. A range of impacts has been identified at a variety of spatial and temporal scales. Chemical contamination and sewage disposal on the continent have been found to be long-lived, with contemporary sewage management practices at many coastal stations insufficient to prevent local contamination. Human activities, particularly construction and transport, have affected Antarctic flora and fauna and a small number of non-indigenous plant and animal species has become established on some of the Antarctic Peninsula and sub Antarctic islands. There is little indication of recovery of overexploited fish stocks, and ramifications of fishing activity on bycatch species and the ecosystem could also be far-reaching. The Antarctic Treaty System and its instruments, in particular the Convention for the Conservation of Antarctic Marine Living Resources (CCAMLR) and the Environmental Protocol, provide a framework within which management of human activities take place. In order to ensure comprehensive protection of the Antarctic environment, including its intrinsic, wilderness and scientific values in the face of the continuing expansion of human activities in Antarctica, a more effective implementation of a wide range of measures is essential. These include effective environmental impact assessments, long-term monitoring, mitigation measures for non-indigenous species, ecosystem-based management of living resources, and increased regulation of National Antarctic

  17. Postural challenge affects motor cortical activity in young and old adults.

    PubMed

    Papegaaij, Selma; Taube, Wolfgang; van Keeken, Helco G; Otten, Egbert; Baudry, Stéphane; Hortobágyi, Tibor

    2016-01-01

    When humans voluntarily activate a muscle, intracortical inhibition decreases. Such a decrease also occurs in the presence of a postural challenge and more so with increasing age. Here, we examined age-related changes in motor cortical activity during postural and non-postural contractions with varying levels of postural challenge. Fourteen young (age 22) and twelve old adults (age 70) performed three conditions: (1) voluntary contraction of the soleus muscle in sitting and (2) leaning forward while standing with and (3) without being supported. Subthreshold transcranial magnetic stimulation was applied to the soleus motor area suppressing ongoing EMG, as an index of motor cortical activity. The area of EMG suppression was ~60% smaller (p<0.05) in unsupported vs. supported leaning and sitting, with no difference between these latter two conditions (p>0.05). Even though in absolute terms young compared with old adults leaned farther (p=0.018), there was no age effect or an age by condition interaction in EMG suppression. Leaning closer to the maximum without support correlated with less EMG suppression (rho=-0.44, p=0.034). We conclude that the critical factor in modulating motor cortical activity was postural challenge and not contraction aim or posture. Age did not affect the motor control strategy as quantified by the modulation of motor cortical activity, but the modulation appeared at a lower task difficulty with increasing age.

  18. Does lunisolar gravitational tide affect the activity of animals?

    NASA Astrophysics Data System (ADS)

    Deshcherevskii, A. V.; Sidorin, A. Ya.

    2010-12-01

    Multiyear time series obtained by the continuous instrumental monitoring of the electrical activity (EA) of weakly electric fish Gnathonemus leopoldianus and the motor activity (MA) of the freshwater catfish Hoplosternum thoracatum and the cockroach Blaberus craniifer are compared to the parameters of the lunisolar gravitational tide. These curves are observed to be very similar for a large number of time intervals. However, a more detailed analysis shows this to be only a superficial resemblance caused by the closeness of the periods of diurnal and semidiurnal rhythms of bioindicator activity (the dominant rhythms in EA and MA patterns) and the periods of main gravitational tidal waves. It is concluded that the lunisolar gravitational tide has no significant effect on animal behavior in our experiment.

  19. Human and nature-caused hazards: the affect heuristic causes biased decisions.

    PubMed

    Siegrist, Michael; Sütterlin, Bernadette

    2014-08-01

    People are more concerned about the negative consequences of human hazards compared with natural hazards. Results of four experiments show that the same negative outcome (e.g., number of birds killed by an oil spill) was more negatively evaluated when caused by humans than when caused by nature. Results further show that when identical risk information was provided, participants evaluated nuclear power more negatively compared with solar power. The affect associated with the hazard per se influenced the interpretation of the new information. Furthermore, the affect experienced in the situation fully mediated the evaluation of the negative outcomes of a hazard. People's reliance on the affect heuristic is a challenge for acceptance of cost-benefit analyses because equally negative outcomes are differently evaluated depending on the cause. Symbolically significant information and the affect evoked by this information may result in biased and riskier decisions.

  20. Hemagglutinin activity of human plasma fibronectin.

    PubMed

    Vuento, M

    1979-09-01

    Purified human plasma fibronectin at concentrations of about 30 microgram/ml was found to agglutinate trypsin-treated erythrocytes from certain species. The hemagglutination reaction was inhibited by specific antibodies to fibronectin, by relatively low concentrations of polyamines and by higher concentrations of basic amino acids and nonacetylated amino sugars. The divalent cations Ca2+ and Mg2+ and the chelating agent ethylenediaminetetraacetate did not affect the reaction. None of the neutral amino acids, neutral sugars or polyanions tested was inhibitory. The results imply that plasma fibronectin is capable of interacting with cell surfaces and support the idea of a similarity between cellular and plasma fibronectins.

  1. Early life stress affects limited regional brain activity in depression.

    PubMed

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-05-03

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients.

  2. Early life stress affects limited regional brain activity in depression

    PubMed Central

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-01-01

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients. PMID:27138376

  3. The brain's emotional foundations of human personality and the Affective Neuroscience Personality Scales.

    PubMed

    Davis, Kenneth L; Panksepp, Jaak

    2011-10-01

    Six of the primary-process subcortical brain emotion systems - SEEKING, RAGE, FEAR, CARE, GRIEF and PLAY - are presented as foundational for human personality development, and hence as a potentially novel template for personality assessment as in the Affective Neurosciences Personality Scales (ANPS), described here. The ANPS was conceptualized as a potential clinical research tool, which would help experimentalists and clinicians situate subjects and clients in primary-process affective space. These emotion systems are reviewed in the context of a multi-tiered framing of consciousness spanning from primary affect, which encodes biological valences, to higher level tertiary (thought mediated) processing. Supporting neuroscience research is presented along with comparisons to Cloninger's Temperament and Character Inventory and the Five Factor Model (FFM). Suggestions are made for grounding the internal structure of the FFM on the primal emotional systems recognized in affective neuroscience, which may promote substantive dialog between human and animal research traditions. Personality is viewed in the context of Darwinian "continuity" with the inherited subcortical brain emotion systems being foundational, providing major forces for personality development in both humans and animals, and providing an affective infrastructure for an expanded five factor descriptive model applying to normal and clinical human populations as well as mammals generally. Links with ontogenetic and epigenetic models of personality development are also presented. Potential novel clinical applications of the CARE maternal-nurturance system and the PLAY system are also discussed.

  4. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.

    PubMed

    Enard, Wolfgang; Gehre, Sabine; Hammerschmidt, Kurt; Hölter, Sabine M; Blass, Torsten; Somel, Mehmet; Brückner, Martina K; Schreiweis, Christiane; Winter, Christine; Sohr, Reinhard; Becker, Lore; Wiebe, Victor; Nickel, Birgit; Giger, Thomas; Müller, Uwe; Groszer, Matthias; Adler, Thure; Aguilar, Antonio; Bolle, Ines; Calzada-Wack, Julia; Dalke, Claudia; Ehrhardt, Nicole; Favor, Jack; Fuchs, Helmut; Gailus-Durner, Valérie; Hans, Wolfgang; Hölzlwimmer, Gabriele; Javaheri, Anahita; Kalaydjiev, Svetoslav; Kallnik, Magdalena; Kling, Eva; Kunder, Sandra; Mossbrugger, Ilona; Naton, Beatrix; Racz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Busch, Dirk H; Graw, Jochen; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Quintanilla-Martinez, Leticia; Schulz, Holger; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Fisher, Simon E; Morgenstern, Rudolf; Arendt, Thomas; de Angelis, Martin Hrabé; Fischer, Julia; Schwarz, Johannes; Pääbo, Svante

    2009-05-29

    It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia. In the striatum, a part of the basal ganglia affected in humans with a speech deficit due to a nonfunctional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one nonfunctional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans.

  5. Factors affecting the adsorption of chromium (VI) on activated carbon

    SciTech Connect

    Yavuz, R.; Orbak, I.; Karatepe, N.

    2006-09-15

    The aim of this investigation was to determine the adsorption behavior of chromium (VI) on two different activated carbon samples produced from Tuncbilek lignite. The effects of the initial chromium (VI) concentration (250-1000 mg/L), temperature (297-323 K) and pH (2.0-9.5) on adsorption were investigated systematically. The effectiveness of the parameters on chromium adsorption was found to be in the order of pH, the initial Cr(VI) concentration and the temperature. Increasing the pH from 2.0 to 9.5 caused a decrease in adsorption. However, the adsorption was increased by increasing the initial Cr(VI) concentration and temperature. The multilinear mathematical model was also developed to predict the Cr(VI) adsorption on activated carbon samples within the experimental conditions.

  6. How absorbed hydrogen affects the catalytic activity of transition metals.

    PubMed

    Aleksandrov, Hristiyan A; Kozlov, Sergey M; Schauermann, Swetlana; Vayssilov, Georgi N; Neyman, Konstantin M

    2014-12-01

    Heterogeneous catalysis is commonly governed by surface active sites. Yet, areas just below the surface can also influence catalytic activity, for instance, when fragmentation products of catalytic feeds penetrate into catalysts. In particular, H absorbed below the surface is required for certain hydrogenation reactions on metals. Herein, we show that a sufficient concentration of subsurface hydrogen, H(sub) , may either significantly increase or decrease the bond energy and the reactivity of the adsorbed hydrogen, H(ad) , depending on the metal. We predict a representative reaction, ethyl hydrogenation, to speed up on Pd and Pt, but to slow down on Ni and Rh in the presence of H(sub) , especially on metal nanoparticles. The identified effects of subsurface H on surface reactivity are indispensable for an atomistic understanding of hydrogenation processes on transition metals and interactions of hydrogen with metals in general.

  7. Assessing the impact of human activities on British Columbia's estuaries.

    PubMed

    Robb, Carolyn K

    2014-01-01

    The world's marine and coastal ecosystems are under threat and single-sector management efforts have failed to address those threats. Scientific consensus suggests that management should evolve to focus on ecosystems and their human, ecological, and physical components. Estuaries are recognized globally as one of the world's most productive and most threatened ecosystems and many estuarine areas in British Columbia (BC) have been lost or degraded. To help prioritize activities and areas for regional management efforts, spatial information on human activities that adversely affect BC's estuaries was compiled. Using statistical analyses, estuaries were assigned to groups facing related threats that could benefit from similar management. The results show that estuaries in the most populated marine ecosections have the highest biological importance but also the highest impacts and the lowest levels of protection. This research is timely, as it will inform ongoing marine planning, land acquisition, and stewardship efforts in BC.

  8. Impaired suppressor activity in children affected by coeliac disease.

    PubMed Central

    Pignata, C; Troncone, R; Monaco, G; Ciriaco, M; Farris, E; Carminati, G; Auricchio, S

    1985-01-01

    Immunoregulatory cells were enumerated in 19 coeliac disease children on a gluten free diet by means of monoclonal antibodies that define total T lymphocytes (T3), helper/inducer T cells (T4), suppressor/cytotoxic T cells (T8) and monocytes (M1), as well as by means of surface receptors for Fc fragments of IgM and IgG (T mu and T gamma, respectively). In addition, suppressor cell function was assessed in 17 coeliac disease patients by examining the ability of concanavalin-A (Con-A)-activated suppressor cells to inhibit autologous cell response to mitogenic stimulus as compared with age-matched controls. No statistically significant differences were found in the percentages of subsets defined by monoclonal antibodies between coeliac disease patients and age-matched controls, whereas coeliac disease patients had a significant decrease of the subpopulation bearing membrane receptor for Fc fragment of IgG. Mean value was 8.5% in coeliac patients versus 13.4% in age-matched controls. In the functional assay, mononuclear cells from 10 out of 17 coeliac disease patients either totally or partially failed to suppress responder cells after Con-A-activation. This defect is not related to HLA-DR status, because no difference was found between patients-HLA-matched and unmatched normal individuals. In this assay, mononuclear cells of three coeliac disease patients with low suppressor activity were able to inhibit responder cells to the same extent as controls, when indomethacin was used to block prostaglandin production in the induction phase of Con-A-activated suppressor cells. Our results suggest that an abnormality in immunoregulation may play a role in the pathogenesis of coeliac disease. PMID:3156076

  9. Seasonal Pacing - Match Importance Affects Activity in Professional Soccer.

    PubMed

    Link, Daniel; de Lorenzo, Michael F

    2016-01-01

    This research explores the influence of match importance on player activity in professional soccer. Therefore, we used an observational approach and analyzed 1,211 matches of German Bundesliga and 2nd Bundesliga. The importance measurement employed is based on post season consequences of teams involved in a match. This means, if a match result could potentially influence the final rank, and this rank would lead to different consequences for a team, such as qualification for Champions League opposed to qualification for Europe League, then this match is classified as important; otherwise not. Activity was quantified by TOTAL DISTANCE COVERED, SPRINTS, FAST RUNS, DUELS, FOULS and ATTEMPTS. Running parameters were recorded using a semi-automatic optical tracking system, while technical variables were collected by professional data loggers. Based on our importance classification, low important matches occurred at the beginning of round 29. A two-way ANOVA indicates significantly increased FAST RUNS (+4%, d = 0.3), DUELS (+16%, d = 1.0) and FOULS (+36%, d = 1.2) in important matches compared to low important ones. For FAST RUNS and FOULS, this effect only exists in Bundesliga. A comparison of the two leagues show that TOTAL DISTANCE COVERED (+3%, d = 0.9), SPRINTS (+25%, d = 1.4) and FAST RUNS (+15%, d = 1.4) are higher compared to 2nd Bundesliga, whilst FOULS is less in Bundesliga (-7%, d = 0.3). No difference in player activity was found between matches at the beginning of a season (round 1-6) and at the end of a season (round 29-34). We conclude that match importance influences player activity in German professional soccer. The most reasonable explanation is a conscious or unconscious pacing strategy, motivated by preserving abilities or preventing injury. Since this tendency mainly exists in Bundesliga, this may suggest that more skilled players show a higher awareness for the need of pacing.

  10. Factors affecting the adsorption of xenon on activated carbon

    SciTech Connect

    Underhill, D.W.; DiCello, D.C.; Scaglia, L.A.; Watson, J.A.

    1986-08-01

    The presence of water vapor was found to interfere strongly with the dynamic adsorption of /sup 133/Xe on coconut-base activated charcoal. The percent loss in the xenon adsorption coefficient was similar to values reported earlier for the adsorption of krypton on humidified charcoal. Attempts to increase the adsorption of xenon by (a) using a petroleum-based adsorbent with an extremely high surface area and (b) by impregnation of the adsorbent with iodine were not successful.

  11. Seasonal Pacing - Match Importance Affects Activity in Professional Soccer

    PubMed Central

    Link, Daniel; de Lorenzo, Michael F.

    2016-01-01

    This research explores the influence of match importance on player activity in professional soccer. Therefore, we used an observational approach and analyzed 1,211 matches of German Bundesliga and 2nd Bundesliga. The importance measurement employed is based on post season consequences of teams involved in a match. This means, if a match result could potentially influence the final rank, and this rank would lead to different consequences for a team, such as qualification for Champions League opposed to qualification for Europe League, then this match is classified as important; otherwise not. Activity was quantified by TOTAL DISTANCE COVERED, SPRINTS, FAST RUNS, DUELS, FOULS and ATTEMPTS. Running parameters were recorded using a semi-automatic optical tracking system, while technical variables were collected by professional data loggers. Based on our importance classification, low important matches occurred at the beginning of round 29. A two-way ANOVA indicates significantly increased FAST RUNS (+4%, d = 0.3), DUELS (+16%, d = 1.0) and FOULS (+36%, d = 1.2) in important matches compared to low important ones. For FAST RUNS and FOULS, this effect only exists in Bundesliga. A comparison of the two leagues show that TOTAL DISTANCE COVERED (+3%, d = 0.9), SPRINTS (+25%, d = 1.4) and FAST RUNS (+15%, d = 1.4) are higher compared to 2nd Bundesliga, whilst FOULS is less in Bundesliga (-7%, d = 0.3). No difference in player activity was found between matches at the beginning of a season (round 1–6) and at the end of a season (round 29–34). We conclude that match importance influences player activity in German professional soccer. The most reasonable explanation is a conscious or unconscious pacing strategy, motivated by preserving abilities or preventing injury. Since this tendency mainly exists in Bundesliga, this may suggest that more skilled players show a higher awareness for the need of pacing. PMID:27281051

  12. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    SciTech Connect

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki; Kawada, Teruo

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  13. The nucleoporin Nup153 affects spindle checkpoint activity due to an association with Mad1

    PubMed Central

    Shimi, Takeshi

    2010-01-01

    The nucleoporin Nup153 is known to play pivotal roles in nuclear import and export in interphase cells and as the cell transitions into mitosis, Nup153 is involved in nuclear envelope breakdown. In this study, we demonstrate that the interaction of Nup153 with the spindle assembly checkpoint protein Mad1 is important in the regulation of the spindle checkpoint. Overexpression of human Nup153 in HeLa cells leads to the appearance of multinucleated cells and induces the formation of multipolar spindles. Importantly, it causes inactivation of the spindle checkpoint due to hypophosphorylation of Mad1. Depletion of Nup153 using RNA interference results in the decline of Mad1 at nuclear pores during interphase and more significantly causes a delayed dissociation of Mad1 from kinetochores in metaphase and an increase in the number of unresolved midbodies. In the absence of Nup153 the spindle checkpoint remains active. In vitro studies indicate direct binding of Mad1 to the N-terminal domain of Nup153. Importantly, Nup153 binding to Mad1 affects Mad1's phosphorylation status, but not its ability to interact with Mad2. Our data suggest that Nup153 levels regulate the localization of Mad1 during the metaphase/anaphase transition thereby affecting its phoshorylation status and in turn spindle checkpoint activity and mitotic exit. PMID:21327106

  14. Effects of aircraft noise on human activities

    NASA Technical Reports Server (NTRS)

    Arnoult, M. D.; Gilfillan, L. G.

    1983-01-01

    The effects of aircrft noise on human activities was investigated by developing a battery of tasks (1) representative of a range of human activities and (2) sensitive to the disruptive effects of noise. The noise used were recordings of jet aircraft and helicopter sounds at three lvels of loudness--60, 70, and 80 dB(A). Experiment 1 investigated 12 different cognitive tasks, along with two intelligibility tasks included to validate that the noises were being effective. Interference with intelligibility was essentially the same as found in the research literature, but only inconsistent effects were found on either accuracy or latency of performance on the cognitive tasks. When the tasks were grouped into four categories (Intelligibility, Matching, Verbal, and Arithmetic), reliable differences in rated annoyingness of the noises were related to the task category and to the type of noise (jet or helicopter).

  15. Potential electrostatic interactions in multiple regions affect human metapneumovirus F-mediated membrane fusion.

    PubMed

    Chang, Andres; Hackett, Brent A; Winter, Christine C; Buchholz, Ursula J; Dutch, Rebecca Ellis

    2012-09-01

    The recently identified human metapneumovirus (HMPV) is a worldwide respiratory virus affecting all age groups and causing pneumonia and bronchiolitis in severe cases. Despite its clinical significance, no specific antiviral agents have been approved for treatment of HMPV infection. Unlike the case for most paramyxoviruses, the fusion proteins (F) of a number of strains, including the clinical isolate CAN97-83, can be triggered by low pH. We recently reported that residue H435 in the HRB linker domain acts as a pH sensor for HMPV CAN97-83 F, likely through electrostatic repulsion forces between a protonated H435 and its surrounding basic residues, K295, R396, and K438, at low pH. Through site-directed mutagenesis, we demonstrated that a positive charge at position 435 is required but not sufficient for F-mediated membrane fusion. Arginine or lysine substitution at position 435 resulted in a hyperfusogenic F protein, while replacement with aspartate or glutamate abolished fusion activity. Studies with recombinant viruses carrying mutations in this region confirmed its importance. Furthermore, a second region within the F(2) domain identified as being rich in charged residues was found to modulate fusion activity of HMPV F. Loss of charge at residues E51, D54, and E56 altered local folding and overall stability of the F protein, with dramatic consequences for fusion activity. As a whole, these studies implicate charged residues and potential electrostatic interactions in function, pH sensing, and overall stability of HMPV F.

  16. Glycolate kinase activity in human red cells.

    PubMed

    Fujii, S; Beutler, E

    1985-02-01

    Human red cells manifest glycolate kinase activity. This activity copurifies with pyruvate kinase and is decreased in the red cells of subjects with hereditary pyruvate kinase deficiency. Glycolate kinase activity was detected in the presence of FDP or glucose-1,6-P2. In the presence of 1 mmol/L FDP, the Km for adenosine triphosphate (ATP) was 0.28 mmol/L and a half maximum velocity for glycolate was obtained at 40 mmol/L. The pH optimum of the reaction was over 10.5 With 10 mumol/L FDP, 500 mumol/L glucose-1,6-P2, 2 mmol/L ATP, 5 mmol/L MgCl2, and 50 mmol/L glycolate at pH 7.5, glycolate kinase activity was calculated to be approximately 0.0013 U/mL RBC. In view of this low activity even in the presence of massive amounts of glycolate, the glycolate kinase reaction cannot account for the maintenance of the reported phosphoglycolate level in human red cells.

  17. Anthropogenic activities affecting Arreo Lake (N Spain) during the last 2500 years

    NASA Astrophysics Data System (ADS)

    Corella, J.; Valero-Garces, B. L.; Stefanova, I.; El Amrani, A.; Morellón, M.; Rico, E.; González-Sampériz, P.; Moreno-Caballud, A.; Giralt, S.; Sigro, J.

    2010-12-01

    Arreo Lake is a small (288 ha surface area) karstic lake 25 m deep located at the northwestern edge of the Ebro Basin (NE Spain). The integration of sedimentary facies, element geochemistry, mineralogy, and biological proxies (pollen and diatoms), together with a robust chronological model provided by 15 AMS radiocarbon dating, 137Cs analyses, and varve counting, permitted a reconstruction of the main phases of anthropogenic activity affecting the Arreo Lake dynamic in the context of the climate variability in the Iberian Peninsula during the last two millennia. A high-resolution study of the lacustrine facies and diatoms, combined with their detailed comparison with recent regional instrumental climatic data (1952-2007), limnological monitoring of the lake (1992-2008), and recent land-use changes affecting the lake watershed show the strong influence of human activities in lake dynamics during the last 60 years. The main impacts are a large increase in sediment delivery to the lake after the 1980s, fluctuations in lake level caused by water extraction for irrigation, and changes in the mixing status of the lake. Littoral and distal sediment cores record the long history of the use of natural resources (salt, water, forest and farming) and their significant impacts in the lake during the last 2500 years. Periods of higher anthropogenic activities linked to increased salt production in the nearby Salinas de Añana during the Roman Period and the Early Middle Ages were coincident with deforestation and increased sediment delivery to the lake. The Modern period was characterized by an abrupt increase in the sedimentation rate. Forest expansion and reduced clastic input to the lake were synchronous with documented depopulation of the area during the Late Middle Ages and the 20th century. The synergy between climate and human activities is shown by the correspondence of increased human pressure and more favourable climate conditions, such as it is recorded during the

  18. Streptomycin affects the growth and photochemical activity of the alga Chlorella vulgaris.

    PubMed

    Perales-Vela, Hugo Virgilio; García, Roberto Velasco; Gómez-Juárez, Evelyn Alicia; Salcedo-Álvarez, Martha Ofelia; Cañizares-Villanueva, Rosa Olivia

    2016-10-01

    Antibiotics are increasingly being used in human and veterinary medicine, as well as pest control in agriculture. Recently, their emergence in the aquatic environment has become a global concern. The aim of this study was to evaluate the effect of streptomycin on growth and photosynthetic activity of Chlorella vulgaris after 72h exposure. We found that growth, photosynthetic activity and the content of the D1 protein of photosystem II decreased. Analysis of chlorophyll a fluorescence emission shows a reduction in the energy transfer between the antenna complex and reaction center. Also the activity of the oxygen evolution complex and electron flow between QA and QB were significantly reduced; in contrast, we found an increase in the reduction rate of the acceptor side of photosystem I. The foregoing can be attributed to the inhibition of the synthesis of the D1 protein and perhaps other coded chloroplast proteins that are part of the electron transport chain which are essential for the transformation of solar energy in the photosystems. We conclude that micromolar concentrations of streptomycin can affect growth and photosynthetic activity of Chlorella vulgaris. The accumulation of antibiotics in the environment can become an ecological problem for primary producers in the aquatic environment.

  19. Low-relief landscape modeling with human activities

    NASA Astrophysics Data System (ADS)

    Yan, Q.; Kumar, P.; Anders, A. M.

    2015-12-01

    Intensively managed landscapes (IMLs) in the Midwestern United States have been shaped by repeated glacial events over geologic time scales followed by rapid human modifications for agriculture and artificial drainage that were overlaid on extremely low gradient stream networks. These landscapes are heavily modified by agriculture, artificial drainage, deforestation, urbanization, and wetland destruction. Channel head extension and periodic dredging for channel straightening not only strongly affected hydrologic and geomorphologic response, but also fundamentally alter the energy consumption in the whole river basin. However, it is unclear how the landscape consumes and responds to the extra energy from human activities. Therefore, we evaluate the present-day dynamics of river network from the perspective of of geomorphic equilibrium, hydrological response, and the rate of energy dissipation. Then, we simulate the landscape evolution to discover the tendency of the system. We find that channel head extension and straightening increases the rate of energy dissipation and pushes the river network further away from equilibrium condition. From our numerical model simulation, extending and maintaining the ditches in the river network can cause large ridge migration, river network redistribution, and enlargement of the drainage basin area. Our research demonstrates how the river basin responds to human activities in glaciated landscape, and how it is likely to behave with artificial modifications on the topography in the future. We attribute the legacy to drainage basin reorganization and theorized that humans can have a lasting impact on the landscape even after active management has ceased.

  20. Lysyl oxidase activity in human normal skins and postburn scars.

    PubMed

    Hayakawa, T; Hino, N; Fuyamada, H; Nagatsu, T; Aoyama, H

    1976-09-06

    Lysyl oxidase activity of human normal skins derived from the frontal thighs of 33 subjects showed large variations and the mean value was 11 455 +/- 7 172 (S.D.) cpm/g of wet weight tissue. The age of lesion affected the lysyl oxidase activity in postburn scars. Granulation tissues showed a fairly low activity; however, the activity increased sharply within 2--3 months, and reached a significantly higher value than that of normal skin. The high level of activity continued for up to 2--3 years, then gradually decreased to normal range after 5 years or so. Lysyl oxidase activity was detected only after 4 M urea treatment of tissues. Benzylamine oxidase activity also showed large variations in both normal skins and postburn scars, with mean values of: 0.128 +/- 0.077 (S.D.) and 0.145 +/- 0.090 (S.D.) mmol/g of wet weight/h, respectively. No correlation was observed between lysyl oxidase and benzylamine oxidase activities. The granulation tissues showed significantly high values of benzylamine oxidase activity in contrast to the low values of lysyl oxidase activity.

  1. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.

  2. Soil biological activity as affected by tillage intensity

    NASA Astrophysics Data System (ADS)

    Gajda, A.; Przewłoka, B.

    2012-02-01

    The effect of tillage intensity on changes of microbiological activity and content of particulate organic matter in soil under winter wheat duirng 3 years was studied. Microbial response related to the tillage-induced changes in soil determined on the content of biomass C and N, the rate of CO2 evolution, B/F ratio, the activity of dehydrogenases, acid and alkaline phosphatases, soil C/N ratio and microbial biomass C/N ratio confirmed the high sensitivity of soil microbial populations to the tillage system applied. After three year studies, the direct sowing system enhanced the increase of labile fraction of organic matter content in soil. There were no significant changes in the labile fraction quantity observed in soil under conventional tillage. Similar response related to the tillage intensity was observed in particulate organic matter quantities expressed as a percentage of total organic matter in soil. A high correlation coefficients calculated between contents of soil microbial biomass C and N, particulate organic matter and potentially mineralizable N, and the obtained yields of winter wheat grown on experimental fields indicated on a high importance of biological quality of status of soil for agricultural crop production.

  3. A functional MiR-124 binding-site polymorphism in IQGAP1 affects human cognitive performance.

    PubMed

    Yang, Lixin; Zhang, Rui; Li, Ming; Wu, Xujun; Wang, Jianhong; Huang, Lin; Shi, Xiaodong; Li, Qingwei; Su, Bing

    2014-01-01

    As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a marked effect on cognitive performance. IQ motif containing GTPase activating protein 1 (IQGAP1), a scaffold protein, affects learning and memory in a dose-dependent manner. Its expression is regulated by miR-124 through the binding sites in the 3'UTR, where a SNP (rs1042538) exists in the core-binding motif. Here we showed that this SNP can influence the miR-target interaction both in vitro and in vivo. Individuals carrying the derived T alleles have higher IQGAP1 expression in the brain as compared to the ancestral A allele carriers. We observed a significant and male-specific association between rs1042538 and tactile performances in two independent cohorts. Males with the derived allele displayed higher tactual performances as compared to those with the ancestral allele. Furthermore, we found a highly diverged allele-frequency distribution of rs1042538 among world human populations, likely caused by natural selection and/or recent population expansion. These results suggest that current human populations still carry sequence variations that affect cognitive performances and that these genetic variants may likely have been subject to comparatively recent natural selection.

  4. [Disclosure of human immunodeficiency virus diagnosis in children and adolescents affected by it and their caregivers].

    PubMed

    Malanca, Adriana; Foradori, Irene; Stankievich, Erica; Pandullo, Hugo; Losso, Marcelo

    2017-04-01

    Children and adolescents need to know about their health or that of their parents. However, families affected by human immunodeficiency virus often delay disclosure of diagnosis for fear of stigma or discrimination or simply because they wonder when and how to communicate it. We present the experience of implementing a program to "reveal" the human immunodeficiency virus diagnosis to children, adolescents and caregivers. The aim was to describe and understand the impact of disclosure and to collaborate on actions to improve comprehensive care for families living with human immunodeficiency virus.

  5. Activation of human factor IX (Christmas factor).

    PubMed Central

    Di Scipio, R G; Kurachi, K; Davie, E W

    1978-01-01

    Human Factor IX (Christmas factor) is a single-chain plasma glycoprotein (mol wt 57,000) that participates in the middle phase of the intrinsic pathway of blood coagulation. It is present in plasma as a zymogen and is converted to a serine protease, Factor IXabeta, by Factor XIa (activated plasma thromboplastin antecedent) in the presence of calcium ions. In the activation reaction, two internal peptide bonds are hydrolyzed in Factor IX. These cleavages occur at a specific arginyl-alanine peptide bond and a specific arginyl-valine peptide bond. This results in the release of an activation peptide (mol wt approximately equal to 11,000) from the internal region of the precursor molecule and the generation of Factor IXabeta (mol wt approximately equal to 46,000). Factor IXabeta is composed of a light chain (mol wt approximately equal to 18,000) and a heavy chain (mol wt approximately equal to 28,000), and these chains are held together by a disulfide bond(s). The light chain originates from the amino terminal portion of the precursor molecule and has an amino terminal sequence of Tyr-Asn-Ser-Gly-Lys. The heavy chain originates from the carboxyl terminal region of the precursor molecule and contains an amino terminal sequence of Val-Val-Gly-Gly-Glu. The heavy chain of Factor IXabeta also contains the active site sequence of Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro. The active site serine residue is shown in capital letters. Factor IX is also converted to Factor IXaalpha by a protease from Russell's viper venom. This activation reaction, however, occurs in a single step and involves only the cleavage of the internal arginyl-valine peptide bond. Human Factor IXabeta was inhibited by human antithrombin III by the formation of a one-to-one complex of enzyme and inhibitor. In this reaction, the inhibitor was tightly bound to the heavy chain of the enzyme. These data indicate that the mechanism of activation of human Factor IX and its

  6. Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

    PubMed Central

    Sowndhararajan, Kandhasamy; Kim, Songmun

    2016-01-01

    The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG). The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–50 Hz), and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the

  7. Control of mechanically activated polymersome fusion: Factors affecting fusion

    DOE PAGES

    Henderson, Ian M.; Paxton, Walter F.

    2014-12-15

    Previously we have studied the mechanically-activated fusion of extruded (200 nm) polymer vesicles into giant polymersomes using agitation in the presence of salt. In this study we have investigated several factors contributing to this phenomenon, including the effects of (i) polymer vesicle concentration, (ii) agitation speed and duration, and iii) variation of the salt and its concentration. It was found that increasing the concentration of the polymer dramatically increases the production of giant vesicles through the increased collisions of polymersomes. Our investigations also found that increasing the frequency of agitation increased the efficiency of fusion, though ultimately limited the sizemore » of vesicle which could be produced due to the high shear involved. Finally it was determined that salt-mediation of the fusion process was not limited to NaCl, but is instead a general effect facilitated by the presence of solvated ionic compounds, albeit with different salts initiating fusion at different concentration.« less

  8. Control of mechanically activated polymersome fusion: Factors affecting fusion

    SciTech Connect

    Henderson, Ian M.; Paxton, Walter F.

    2014-12-15

    Previously we have studied the mechanically-activated fusion of extruded (200 nm) polymer vesicles into giant polymersomes using agitation in the presence of salt. In this study we have investigated several factors contributing to this phenomenon, including the effects of (i) polymer vesicle concentration, (ii) agitation speed and duration, and iii) variation of the salt and its concentration. It was found that increasing the concentration of the polymer dramatically increases the production of giant vesicles through the increased collisions of polymersomes. Our investigations also found that increasing the frequency of agitation increased the efficiency of fusion, though ultimately limited the size of vesicle which could be produced due to the high shear involved. Finally it was determined that salt-mediation of the fusion process was not limited to NaCl, but is instead a general effect facilitated by the presence of solvated ionic compounds, albeit with different salts initiating fusion at different concentration.

  9. Definition and Measurement in the Affective Domain: Appreciation of Human Accomplishments.

    ERIC Educational Resources Information Center

    Campbell, Paul B.; Beers, Joan S.

    The first three levels of the taxonomy in the affective domain guided the development of two inventories--the Pennsylvania Inventory of Cultural Appreciations (PICA) for 11th graders and Things People Do (TPD) for 5th graders--to measure appreciation of human accomplishments in seven areas: politics, sciences, sports, literature, visual arts,…

  10. Affective Education: A Teacher's Manual to Promote Student Self-Actualization and Human Relations Skills.

    ERIC Educational Resources Information Center

    Snyder, Thomas R.

    This teacher's manual presents affective education as a program to promote student self-actualization and human relations skills. Abraham Maslow's hierarchy of needs and Erik Erikson's life stages of psychosocial development form the conceptual base for this program. The goals and objectives of this manual are concerned with problem-solving…

  11. Human-Computer Interaction: A Review of the Research on Its Affective and Social Aspects.

    ERIC Educational Resources Information Center

    Deaudelin, Colette; Dussault, Marc; Brodeur, Monique

    2003-01-01

    Discusses a review of 34 qualitative and non-qualitative studies related to affective and social aspects of student-computer interactions. Highlights include the nature of the human-computer interaction (HCI); the interface, comparing graphic and text types; and the relation between variables linked to HCI, mainly trust, locus of control,…

  12. Immunosuppressive drugs affect high-mannose/hybrid N-glycans on human allostimulated leukocytes.

    PubMed

    Pocheć, Ewa; Bocian, Katarzyna; Ząbczyńska, Marta; Korczak-Kowalska, Grażyna; Lityńska, Anna

    2015-01-01

    N-glycosylation plays an important role in the majority of physiological and pathological processes occurring in the immune system. Alteration of the type and abundance of glycans is an element of lymphocyte differentiation; it is also common in the development of immune-mediated inflammatory diseases. The N-glycosylation process is very sensitive to different environmental agents, among them the pharmacological environment of immunosuppressive drugs. Some results show that high-mannose oligosaccharides have the ability to suppress different stages of the immune response. We evaluated the effects of cyclosporin A (CsA) and rapamycin (Rapa) on high-mannose/hybrid-type glycosylation in human leukocytes activated in a two-way mixed leukocyte reaction (MLR). CsA significantly reduced the number of leukocytes covered by high-mannose/hybrid N-glycans, and the synergistic action of CsA and Rapa led to an increase of these structures on the remaining leukocytes. This is the first study indicating that β1 and β3 integrins bearing high-mannose/hybrid structures are affected by Rapa and CsA. Rapa taken separately and together with CsA changed the expression of β1 and β3 integrins and, by regulating the protein amount, increased the oligomannose/hybrid-type N-glycosylation on the leukocyte surface. We suggest that the changes in the glycosylation profile of leukocytes may promote the development of tolerance in transplantation.

  13. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

    PubMed Central

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  14. How Lipid Membranes Affect Pore Forming Toxin Activity.

    PubMed

    Rojko, Nejc; Anderluh, Gregor

    2015-12-15

    , events associated with pore formation can modulate properties of the lipid membrane and affect its organization. Model membranes do not necessarily reproduce the physicochemical properties of the native cellular membrane, and caution is needed when transferring results from model to native lipid membranes. In this context, the utilization of novel approaches that enable studying PFTs on living cells at a single molecule level should reveal complex protein-lipid membrane interactions in greater detail.

  15. Glutamatergic activation of anterior cingulate cortex mediates the affective component of visceral pain memory in rats.

    PubMed

    Yan, Ni; Cao, Bing; Xu, Jiahe; Hao, Chun; Zhang, Xu; Li, Ying

    2012-01-01

    Studies of both humans and animals suggest that anterior cingulate cortex (ACC) is important for processing pain perception. We identified that perigenul ACC (pACC) sensitization and enhanced visceral pain in a visceral hypersensitive rat in previous studies. Pain contains both sensory and affective dimensions. Teasing apart the mechanisms that control the neural pathways mediating pain affect and sensation in nociceptive behavioral response is a challenge. In this study, using a rodent visceral pain assay that combines the colorectal distension (CRD)-induced visceromotor response (VMR) with the conditioning place avoidance (CPA), we measured a learned behavior that directly reflects the affective component of visceral pain. When CRD was paired with a distinct environment context, the rats spent significantly less time in this compartment on the post-conditioning test days as compared with the pre-conditioning day. Effects were lasted for 14 days. Bilateral pACC lesion significantly reduced CPA scores without reducing acute visceral pain behaviors (CRD-induced VMR). Bilateral administration of non-NMDA receptor antagonist CNQX or NMDA receptor antagonist AP5 into the pACC decreased the CPA scores. AP5 or CNQX at dose of 400 mM produced about 70% inhibition of CRD-CPA in the day 1, 4 and 7, and completely abolished the CPA in the day 14 after conditioning. We concluded that neurons in the pACC are necessary for the "aversiveness" of visceral nociceptor stimulation. pACC activation is critical for the memory processing involved in long-term negative affective state and prediction of aversive stimuli by contextual cue.

  16. Variability in affective activation predicts non-suicidal self-injury in eating disorders.

    PubMed

    Vansteelandt, Kristof; Claes, Laurence; Muehlenkamp, Jennifer; De Cuyper, Kathleen; Lemmens, Jos; Probst, Michel; Vanderlinden, Johan; Pieters, Guido

    2013-03-01

    We examined whether affective variability can predict non-suicidal self-injury (NSSI) in eating disorders. Affect was represented by valence (positive versus negative) and activation (high versus low). Twenty-one patients with anorexia nervosa-restricting type, 18 patients with anorexia nervosa-binge-purging type and 20 patients with bulimia nervosa reported their momentary affect at nine random times a day during a one week period using a hand-held computer. Affective variability was calculated as the within-person standard deviation of valence and activation over time. Results indicate that patients displaying greater variability in activation and using selective serotonin reuptake inhibitors have a higher probability to engage in lifetime NSSI after adjustment for depression and borderline personality disorder. Neither variability of valence nor mean level of valence and activation had any predictive association with engaging in NSSI. It is suggested that the treatment of NSSI should focus on affect stabilization rather than reducing negative affect.

  17. Cognitive-affective neural plasticity following active-controlled mindfulness intervention.

    PubMed

    Allen, Micah; Dietz, Martin; Blair, Karina S; van Beek, Martijn; Rees, Geraint; Vestergaard-Poulsen, Peter; Lutz, Antoine; Roepstorff, Andreas

    2012-10-31

    Mindfulness meditation is a set of attention-based, regulatory, and self-inquiry training regimes. Although the impact of mindfulness training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles. To resolve this question we conducted a fully randomized 6 week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active-control group. We measured behavioral metacognition and whole-brain blood oxygenation level-dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex, medial prefrontal cortex, and right anterior insula during negative valence processing. Our findings highlight the importance of active control in MT research, indicate unique neural mechanisms for progressive stages of mindfulness training, and suggest that optimal application of MT may differ depending on context, contrary to a one-size-fits-all approach.

  18. A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway

    PubMed Central

    Praetorius, Christian; Grill, Christine; Stacey, Simon N.; Metcalf, Alexander M.; Gorkin, David U.; Robinson, Kathleen C.; Van Otterloo, Eric; Kim, Reuben S.Q.; Bergsteinsdottir, Kristin; Ogmundsdottir, Margret H.; Magnusdottir, Erna; Mishra, Pravin J.; Davis, Sean R.; Guo, Theresa; Zaidi, M. Raza; Helgason, Agnar S.; Sigurdsson, Martin I.; Melzer, Paul S.; Merlino, Glenn; Petit, Valerie; Larue, Lionel; Loftus, Stacie K.; Adams, David R.; Sobhiafshar, Ulduz; Emre, N. C. Tolga; Pavan, William J.; Cornell, Robert; Smith, Aaron G.; McCallion, Andrew S.; Fisher, David E.; Stefansson, Kari; Sturm, Richard A.; Steingrímsson, Eiríkur

    2013-01-01

    Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect non-coding regions. A single nucleotide polymorphism (SNP) within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes and brown hair color. Here we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor which together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a non-coding polymorphism that affects a phenotype by modulating a developmental gene regulatory network. PMID:24267888

  19. Tasting calories differentially affects brain activation during hunger and satiety.

    PubMed

    van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

    2015-02-15

    An important function of eating is ingesting energy. Our objectives were to assess whether oral exposure to caloric and non-caloric stimuli elicits discriminable responses in the brain and to determine in how far these responses are modulated by hunger state and sweetness. Thirty women tasted three stimuli in two motivational states (hunger and satiety) while their brain responses were measured using functional magnetic resonance imaging in a randomized crossover design. Stimuli were solutions of sucralose (sweet, no energy), maltodextrin (non-sweet, energy) and sucralose+maltodextrin (sweet, energy). We found no main effect of energy content and no interaction between energy content and sweetness. However, there was an interaction between hunger state and energy content in the median cingulate (bilaterally), ventrolateral prefrontal cortex, anterior insula and thalamus. This indicates that the anterior insula and thalamus, areas in which hunger state and taste of a stimulus are integrated, also integrate hunger state with caloric content of a taste stimulus. Furthermore, in the median cingulate and ventrolateral prefrontal cortex, tasting energy resulted in more activation during satiety compared to hunger. This finding indicates that these areas, which are known to be involved in processes that require approach and avoidance, are also involved in guiding ingestive behavior. In conclusion, our results suggest that energy sensing is a hunger state dependent process, in which the median cingulate, ventrolateral prefrontal cortex, anterior insula and thalamus play a central role by integrating hunger state with stimulus relevance.

  20. Might as Well Jump: Sound Affects Muscle Activation in Skateboarding

    PubMed Central

    Cesari, Paola; Camponogara, Ivan; Papetti, Stefano; Rocchesso, Davide; Fontana, Federico

    2014-01-01

    The aim of the study is to reveal the role of sound in action anticipation and performance, and to test whether the level of precision in action planning and execution is related to the level of sensorimotor skills and experience that listeners possess about a specific action. Individuals ranging from 18 to 75 years of age - some of them without any skills in skateboarding and others experts in this sport - were compared in their ability to anticipate and simulate a skateboarding jump by listening to the sound it produces. Only skaters were able to modulate the forces underfoot and to apply muscle synergies that closely resembled the ones that a skater would use if actually jumping on a skateboard. More importantly we showed that only skaters were able to plan the action by activating anticipatory postural adjustments about 200 ms after the jump event. We conclude that expert patterns are guided by auditory events that trigger proper anticipations of the corresponding patterns of movements. PMID:24619134

  1. Social decisions affect neural activity to perceived dynamic gaze

    PubMed Central

    Latinus, Marianne; Love, Scott A.; Rossi, Alejandra; Parada, Francisco J.; Huang, Lisa; Conty, Laurence; George, Nathalie; James, Karin

    2015-01-01

    Gaze direction, a cue of both social and spatial attention, is known to modulate early neural responses to faces e.g. N170. However, findings in the literature have been inconsistent, likely reflecting differences in stimulus characteristics and task requirements. Here, we investigated the effect of task on neural responses to dynamic gaze changes: away and toward transitions (resulting or not in eye contact). Subjects performed, in random order, social (away/toward them) and non-social (left/right) judgment tasks on these stimuli. Overall, in the non-social task, results showed a larger N170 to gaze aversion than gaze motion toward the observer. In the social task, however, this difference was no longer present in the right hemisphere, likely reflecting an enhanced N170 to gaze motion toward the observer. Our behavioral and event-related potential data indicate that performing social judgments enhances saliency of gaze motion toward the observer, even those that did not result in gaze contact. These data and that of previous studies suggest two modes of processing visual information: a ‘default mode’ that may focus on spatial information; a ‘socially aware mode’ that might be activated when subjects are required to make social judgments. The exact mechanism that allows switching from one mode to the other remains to be clarified. PMID:25925272

  2. Social decisions affect neural activity to perceived dynamic gaze.

    PubMed

    Latinus, Marianne; Love, Scott A; Rossi, Alejandra; Parada, Francisco J; Huang, Lisa; Conty, Laurence; George, Nathalie; James, Karin; Puce, Aina

    2015-11-01

    Gaze direction, a cue of both social and spatial attention, is known to modulate early neural responses to faces e.g. N170. However, findings in the literature have been inconsistent, likely reflecting differences in stimulus characteristics and task requirements. Here, we investigated the effect of task on neural responses to dynamic gaze changes: away and toward transitions (resulting or not in eye contact). Subjects performed, in random order, social (away/toward them) and non-social (left/right) judgment tasks on these stimuli. Overall, in the non-social task, results showed a larger N170 to gaze aversion than gaze motion toward the observer. In the social task, however, this difference was no longer present in the right hemisphere, likely reflecting an enhanced N170 to gaze motion toward the observer. Our behavioral and event-related potential data indicate that performing social judgments enhances saliency of gaze motion toward the observer, even those that did not result in gaze contact. These data and that of previous studies suggest two modes of processing visual information: a 'default mode' that may focus on spatial information; a 'socially aware mode' that might be activated when subjects are required to make social judgments. The exact mechanism that allows switching from one mode to the other remains to be clarified.

  3. Does human migration affect international trade? A complex-network perspective.

    PubMed

    Fagiolo, Giorgio; Mastrorillo, Marina

    2014-01-01

    This paper explores the relationships between international human migration and merchandise trade, using a complex-network approach. We firstly compare the topological structure of worldwide networks of human migration and bilateral trade over the period 1960-2000. Next, we ask whether the position of any pair of countries in the migration network affects their bilateral trade flows. We show that: (i) both weighted and binary versions of the networks of international migration and trade are strongly correlated; (ii) such correlations can be mostly explained by country economic/demographic size and geographical distance; and (iii) pairs of countries that are more central in the international-migration network trade more. Our findings suggest that bilateral trade between any two countries is not only affected by the presence of migrants from either countries but also by their relative embeddedness in the complex web of corridors making up the network of international human migration.

  4. Listening to humans walking together activates the social brain circuitry.

    PubMed

    Saarela, Miiamaaria V; Hari, Riitta

    2008-01-01

    Human footsteps carry a vast amount of social information, which is often unconsciously noted. Using functional magnetic resonance imaging, we analyzed brain networks activated by footstep sounds of one or two persons walking. Listening to two persons walking together activated brain areas previously associated with affective states and social interaction, such as the subcallosal gyrus bilaterally, the right temporal pole, and the right amygdala. These areas seem to be involved in the analysis of persons' identity and complex social stimuli on the basis of auditory cues. Single footsteps activated only the biological motion area in the posterior STS region. Thus, hearing two persons walking together involved a more widespread brain network than did hearing footsteps from a single person.

  5. Glyphosate affects the spontaneous motoric activity of intestine at very low doses - in vitro study.

    PubMed

    Chłopecka, Magdalena; Mendel, Marta; Dziekan, Natalia; Karlik, Wojciech

    2014-07-01

    Glyphosate is an active substance of the most popular herbicides worldwide. Its common use results from the belief that it affects exclusively plants. However, studies on glyphosate and its trade formulations reveal that it causes numerous morphological, physiological and biochemical disturbances in cells and organisms of animals, including mammals. Due to the fact that shortly after oral exposure glyphosate is detected in the highest amount in small intestine, the aim of this study was to evaluate the effect of this compound on the spontaneous motoric activity of intestine under in vitro conditions. The experiments were conducted on rat jejunum strips under isotonic conditions. The strips were incubated in buffered (pH 7.35) and non-buffered (pH 5.2) glyphosate solutions ranged from 0.003 to 1.7 g/L. The results indicate that glyphosate applied in buffered solution affects significantly the spontaneous motoric activity of rat isolated jejunum strips. The muscle response is biphasic (miorelaxation accompanied by contraction). The contraction is observed already at a dose of 0.003 g/L and the first significant biphasic reaction at a dose of 0.014 g/L. The incubation of jejunum strips with glyphosate in non-buffered solution (pH 5.2) results in a different reaction. The smooth muscle undergoes only persistent relaxation, which is stronger than the response to glyphosate solution in pH 7.35. Motility disturbances are also observed after glyphosate removal from the incubation solution. The gathered data suggests that glyphosate impairs gastrointestinal strips' motility at concentration that are noticed in human exposed to non-toxic doses of glyphosate.

  6. Physical Human Activity Recognition Using Wearable Sensors.

    PubMed

    Attal, Ferhat; Mohammed, Samer; Dedabrishvili, Mariam; Chamroukhi, Faicel; Oukhellou, Latifa; Amirat, Yacine

    2015-12-11

    This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle). Three main steps describe the activity recognition process: sensors' placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN), Support Vector Machines (SVM), Gaussian Mixture Models (GMM), and Random Forest (RF) as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM) and Hidden Markov Model (HMM), are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

  7. Physical Human Activity Recognition Using Wearable Sensors

    PubMed Central

    Attal, Ferhat; Mohammed, Samer; Dedabrishvili, Mariam; Chamroukhi, Faicel; Oukhellou, Latifa; Amirat, Yacine

    2015-01-01

    This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle). Three main steps describe the activity recognition process: sensors’ placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN), Support Vector Machines (SVM), Gaussian Mixture Models (GMM), and Random Forest (RF) as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM) and Hidden Markov Model (HMM), are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject. PMID:26690450

  8. Culture temperature affects human chondrocyte messenger RNA expression in monolayer and pellet culture systems.

    PubMed

    Ito, Akira; Nagai, Momoko; Tajino, Junichi; Yamaguchi, Shoki; Iijima, Hirotaka; Zhang, Xiangkai; Aoyama, Tomoki; Kuroki, Hiroshi

    2015-01-01

    Cell-based therapy has been explored for articular cartilage regeneration. Autologous chondrocyte implantation is a promising cell-based technique for repairing articular cartilage defects. However, there are several issues such as chondrocyte de-differentiation. While numerous studies have been designed to overcome some of these issues, only a few have focused on the thermal environment that can affect chondrocyte metabolism and phenotype. In this study, the effects of different culture temperatures on human chondrocyte metabolism- and phenotype-related gene expression were investigated in 2D and 3D environments. Human chondrocytes were cultured in a monolayer or in a pellet culture system at three different culture temperatures (32°C, 37°C, and 41°C) for 3 days. The results showed that the total RNA level, normalized to the threshold cycle value of internal reference genes, was higher at lower temperatures in both culture systems. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and citrate synthase (CS), which are involved in glycolysis and the citric acid cycle, respectively, were expressed at similar levels at 32°C and 37°C in pellet cultures, but the levels were significantly lower at 41°C. Expression of the chondrogenic markers, collagen type IIA1 (COL2A1) and aggrecan (ACAN), was higher at 37°C than at 32°C and 41°C in both culture systems. However, this phenomenon did not coincide with SRY (sex-determining region Y)-box 9 (SOX9), which is a fundamental transcription factor for chondrogenesis, indicating that a SOX9-independent pathway might be involved in this phenomenon. In conclusion, the expression of chondrocyte metabolism-related genes at 32°C was maintained or enhanced compared to that at 37°C. However, chondrogenesis-related genes were further induced at 37°C in both culture systems. Therefore, manipulating the culture temperature may be an advantageous approach for regulating human chondrocyte metabolic activity and chondrogenesis.

  9. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    PubMed

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities.

  10. Vanadium promotes hydroxyl radical formation by activated human neutrophils.

    PubMed

    Fickl, Heidi; Theron, Annette J; Grimmer, Heidi; Oommen, Joyce; Ramafi, Grace J; Steel, Helen C; Visser, Susanna S; Anderson, Ronald

    2006-01-01

    This study was undertaken to investigate the effects of vanadium in the +2, +3, +4, and +5 valence states on superoxide generation, myeloperoxidase (MPO) activity, and hydroxyl radical formation by activated human neutrophils in vitro, using lucigenin-enhanced chemiluminescence (LECL), autoiodination, and electron spin resonance with 5,5-dimethyl-l-pyrroline N-oxide as the spin trap, respectively. At concentrations of up to 25 microM, vanadium, in the four different valence states used, did not affect the LECL responses of neutrophils activated with either the chemoattractant, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (1 microM), or the phorbol ester, phorbol 12-myristate 12-acetate (25 ng/ml). However, exposure to vanadium in the +2, +3, and +4, but not the +5, valence states was accompanied by significant augmentation of hydroxyl radical formation by activated neutrophils and attenuation of MPO-mediated iodination. With respect to hydroxyl radical formation, similar effects were observed using cell-free systems containing either hydrogen peroxide (100 microM) or xanthine/xanthine oxidase together with vanadium (+2, +3, +4), while the activity of purified MPO was inhibited by the metal in these valence states. These results demonstrate that vanadium in the +2, +3, and +4 valence states interacts prooxidatively with human neutrophils, competing effectively with MPO for hydrogen peroxide to promote formation of the highly toxic hydroxyl radical.

  11. Valsalva maneuver: Insights into baroreflex modulation of human sympathetic activity

    NASA Technical Reports Server (NTRS)

    Smith, Michael L.; Eckberg, Dwain L.; Fritsch, Janice M.; Beightol, Larry A.; Ellenbogen, Kenneth A.

    1991-01-01

    Valsalva's maneuver, voluntary forced expiration against a closed glottis, is a well-characterized research tool, used to assess the integrity of human autonomic cardiovascular control. Valsalva straining provokes a stereotyped succession of alternating positive and negative arterial pressure and heart rate changes mediated in part by arterial baroreceptors. Arterial pressure changes result primarily from fluctuating levels of venous return to the heart and changes of sympathetic nerve activity. Muscle sympathetic activity was measured directly in nine volunteers to explore quantitatively the relation between arterial pressure and human sympathetic outflow during pressure transients provoked by controlled graded Valsalva maneuvers. Our results underscore several properties of sympathetic regulation during Valsalva straining. First, muscle sympathetic nerve activity changes as a mirror image of changes in arterial pressure. Second, the magnitude of sympathetic augmentation during Valsalva straining predicts phase 4 arterial pressure elevations. Third, post-Valsalva sympathetic inhibition persists beyond the return of arterial and right atrial pressures to baseline levels which reflects an alteration of the normal relation between arterial pressure and muscle sympathetic activity. Therefore, Valsalva straining may have some utility for investigating changes of reflex control of sympathetic activity after space flight; however, measurement of beat-to-beat arterial pressure is essential for this use. The utility of this technique in microgravity can not be determined from these data. Further investigations are necessary to determine whether these relations are affected by the expansion of intrathoracic blood volume associated with microgravity.

  12. The importance of physical activity and sleep for affect on stressful days: Two intensive longitudinal studies.

    PubMed

    Flueckiger, Lavinia; Lieb, Roselind; Meyer, Andrea H; Witthauer, Cornelia; Mata, Jutta

    2016-06-01

    We investigated the potential stress-buffering effect of 3 health behaviors-physical activity, sleep quality, and snacking-on affect in the context of everyday life in young adults. In 2 intensive longitudinal studies with up to 65 assessment days over an entire academic year, students (Study 1, N = 292; Study 2, N = 304) reported stress intensity, sleep quality, physical activity, snacking, and positive and negative affect. Data were analyzed using multilevel regression analyses. Stress and positive affect were negatively associated; stress and negative affect were positively associated. The more physically active than usual a person was on a given day, the weaker the association between stress and positive affect (Study 1) and negative affect (Studies 1 and 2). The better than usual a person's sleep quality had been during the previous night, the weaker the association between stress and positive affect (Studies 1 and 2) and negative affect (Study 2). The association between daily stress and positive or negative affect did not differ as a function of daily snacking (Studies 1 and 2). On stressful days, increasing physical activity or ensuring high sleep quality may buffer adverse effects of stress on affect in young adults. These findings suggest potential targets for health-promotion and stress-prevention programs, which could help reduce the negative impact of stress in young adults. (PsycINFO Database Record

  13. CFTR targeting during activation of human neutrophils.

    PubMed

    Ng, Hang Pong; Valentine, Vincent G; Wang, Guoshun

    2016-12-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, plays critical roles in phagocytic host defense. However, how activated neutrophils regulate CFTR channel distribution subcellularly is not well defined. To investigate, we tested multiple Abs against different CFTR domains, to examine CFTR expression in human peripheral blood neutrophils by flow cytometry. The data confirmed that resting neutrophils had pronounced CFTR expression. Activation of neutrophils with soluble or particulate agonists did not significantly increase CFTR expression level, but induced CFTR redistribution to cell surface. Such CFTR mobilization correlated with cell-surface recruitment of formyl-peptide receptor during secretory vesicle exocytosis. Intriguingly, neutrophils from patients with ΔF508-CF, despite expression of the mutant CFTR, showed little cell-surface mobilization upon stimulation. Although normal neutrophils effectively targeted CFTR to their phagosomes, ΔF508-CF neutrophils had impairment in that process, resulting in deficient hypochlorous acid production. Taken together, activated neutrophils regulate CFTR distribution by targeting this chloride channel to the subcellular sites of activation, and ΔF508-CF neutrophils fail to achieve such targeting, thus undermining their host defense function.

  14. Human Infant Faces Provoke Implicit Positive Affective Responses in Parents and Non-Parents Alike

    PubMed Central

    Senese, Vincenzo Paolo; De Falco, Simona; Bornstein, Marc H.; Caria, Andrea; Buffolino, Simona; Venuti, Paola

    2013-01-01

    Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors. PMID:24282537

  15. Genetic variants in ABCA1 promoter affect transcription activity and plasma HDL level in pigs.

    PubMed

    Dang, Xiao-yong; Chu, Wei-wei; Shi, Heng-chuan; Yu, Shi-gang; Han, Hai-yin; Gu, Shu-Hua; Chen, Jie

    2015-01-25

    Excess accumulation of cholesterol in plasma may result in coronary artery disease. Numerous studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for plasma high density lipoprotein (HDL) formation. Higher plasma levels of HDL are associated with lower risk for cardiovascular disease. Studies of human disease and animal models had shown that an increased hepatic ABCA1 activity relates to an enhanced plasma HDL level. In this study, we hypothesized that functional mutations in the ABCA1 promoter in pigs may affect gene transcription activity, and consequently the HDL level in plasma. The promoter region of ABCA1 was comparatively scanned by direct sequencing with pool DNA of high- and low-HDL groups (n=30 for each group). Two polymorphisms, c. - 608A>G and c. - 418T>A, were revealed with reverse allele distribution in the two groups. The two polymorphisms were completely linked and formed only G-A or A-T haplotypes when genotyped in a larger population (n=526). Furthermore, we found that the G-A/G-A genotype was associated with higher HDL and ABCA1 mRNA level than A-T/A-T genotype. Luciferase assay also revealed that G-A haplotype promoter had higher activity than A-T haplotype. Single-nucleotide mutant assay showed that c.-418T>A was the causal mutation for ABCA1 transcription activity alteration. Conclusively, we identified two completely linked SNPs in porcine ABCA1 promoter region which have influence on the plasma HDL level by altering ABCA1 gene transcriptional activity.

  16. Spreading dynamics following bursty human activity patterns

    NASA Astrophysics Data System (ADS)

    Min, Byungjoon; Goh, K.-I.; Vazquez, Alexei

    2011-03-01

    We study the susceptible-infected model with power-law waiting time distributions P(τ)~τ-α, as a model of spreading dynamics under heterogeneous human activity patterns. We found that the average number of new infections n(t) at time t decays as a power law in the long-time limit, n(t)~t-β, leading to extremely slow prevalence decay. We also found that the exponent in the spreading dynamics β is related to that in the waiting time distribution α in a way depending on the interactions between agents but insensitive to the network topology. These observations are well supported by both the theoretical predictions and the long prevalence decay time in real social spreading phenomena. Our results unify individual activity patterns with macroscopic collective dynamics at the network level.

  17. Pseudo-esterase Activity of Human Albumin

    PubMed Central

    Lockridge, Oksana; Xue, Weihua; Gaydess, Andrea; Grigoryan, Hasmik; Ding, Shi-Jian; Schopfer, Lawrence M.; Hinrichs, Steven H.; Masson, Patrick

    2008-01-01

    Human albumin is thought to hydrolyze esters because multiple equivalents of product are formed for each equivalent of albumin. Esterase activity with p-nitrophenyl acetate has been attributed to turnover at tyrosine 411. However, p-nitrophenyl acetate creates multiple, stable, acetylated adducts, a property contrary to turnover. Our goal was to identify residues that become acetylated by p-nitrophenyl acetate and determine the relationship between stable adduct formation and turnover. Fatty acid-free human albumin was treated with 0.5 mm p-nitrophenyl acetate for 5 min to 2 weeks, or with 10 mm p-nitrophenyl acetate for 48 h to 2 weeks. Aliquots were digested with pepsin, trypsin, or GluC and analyzed by mass spectrometry to identify labeled residues. Only Tyr-411 was acetylated within the first 5 min of reaction with 0.5 mm p-nitrophenyl acetate. After 0.5–6 h there was partial acetylation of 16–17 residues including Asp-1, Lys-4, Lys-12, Tyr-411, Lys-413, and Lys-414. Treatment with 10 mm p-nitrophenyl acetate resulted in acetylation of 59 lysines, 10 serines, 8 threonines, 4 tyrosines, and Asp-1. When Tyr-411 was blocked with diisopropylfluorophosphate or chlorpyrifos oxon, albumin had normal esterase activity with β-naphthyl acetate as visualized on a nondenaturing gel. However, after 82 residues had been acetylated, esterase activity was almost completely inhibited. The half-life for deacetylation of Tyr-411 at pH 8.0, 22 °C was 61 ± 4 h. Acetylated lysines formed adducts that were even more stable. In conclusion, the pseudo-esterase activity of albumin is the result of irreversible acetylation of 82 residues and is not the result of turnover. PMID:18577514

  18. Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPARγ Expression and Activation in Differentiating Mesenchymal Stem Cells

    PubMed Central

    Rivas, Daniel; Akter, Rahima; Duque, Gustavo

    2007-01-01

    Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPARγ2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPARγ, and SREBP-1 were determined by western blot. Finally, DNA binding PPARγ activity was determined using an ELISA-based PPARγ activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPARγ expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPARγ activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPARγ expression and activity. PMID:18274630

  19. Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPARgamma Expression and Activation in Differentiating Mesenchymal Stem Cells.

    PubMed

    Rivas, Daniel; Akter, Rahima; Duque, Gustavo

    2007-01-01

    Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPARgamma2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPARgamma, and SREBP-1 were determined by western blot. Finally, DNA binding PPARgamma activity was determined using an ELISA-based PPARgamma activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPARgamma expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPARgamma activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPARgamma expression and activity.

  20. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

  1. The transcriptional activity of human Chromosome 22

    PubMed Central

    Rinn, John L.; Euskirchen, Ghia; Bertone, Paul; Martone, Rebecca; Luscombe, Nicholas M.; Hartman, Stephen; Harrison, Paul M.; Nelson, F. Kenneth; Miller, Perry; Gerstein, Mark; Weissman, Sherman; Snyder, Michael

    2003-01-01

    A DNA microarray representing nearly all of the unique sequences of human Chromosome 22 was constructed and used to measure global-transcriptional activity in placental poly(A)+ RNA. We found that many of the known, related and predicted genes are expressed. More importantly, our study reveals twice as many transcribed bases as have been reported previously. Many of the newly discovered expressed fragments were verified by RNA blot analysis and a novel technique called differential hybridization mapping (DHM). Interestingly, a significant fraction of these novel fragments are expressed antisense to previously annotated introns. The coding potential of these novel expressed regions is supported by their sequence conservation in the mouse genome. This study has greatly increased our understanding of the biological information encoded on a human chromosome. To facilitate the dissemination of these results to the scientific community, we have developed a comprehensive Web resource to present the findings of this study and other features of human Chromosome 22 at http://array.mbb.yale.edu/chr22. PMID:12600945

  2. Inhibition of human natural killer cell functional activity by human aspartyl β-hydroxylase.

    PubMed

    Huyan, Ting; Li, Qi; Ye, Lin-Jie; Yang, Hui; Xue, Xiao-Ping; Zhang, Ming-Jie; Huang, Qing-Sheng; Yin, Da-Chuan; Shang, Peng

    2014-12-01

    Natural killer (NK) cells are a key component of the innate immune system and play pivotal roles as inflammatory regulators and in tumor surveillance. Human aspartyl β-hydroxylase (HAAH) is a plasma membrane and endoplasmic reticulum protein with hydroxylation activity, which is over-expressed in many malignant neoplasms and can be detected from the sera of tumor patients. HAAH is involved in regulating tumor cell infiltration and metastasis. Escaping from immune surveillance may help tumor cell infiltration and metastasis. However, the effects of HAAH on tumor immune surveillance have not yet been investigated carefully. The present study investigated the potential use of HAAH as an immune regulator of human NK cells. We assessed the effects of recombinant HAAH (r-HAAH) on primary human NK cell morphology, viability, cytotoxicity, apoptosis, receptors expression and cytokine/cytolytic proteins production. Our results demonstrated that r-HAAH negatively affects NK cell activity in a time and dose-dependent manner. It noticeably reduces the viability of the NK cells by increasing apoptosis and necrosis via caspase signaling pathways. Moreover, r-HAAH reduces the NK cell cytotoxicity by inhibiting surface expression of NKG2D, NKp44 and IFN-γ secretion. These findings suggest that one of the ways by which HAAH actively promotes tumor formation and proliferation is by inhibiting NK cell-surveillance activity.

  3. Telomerase activity in human pleural mesothelioma

    PubMed Central

    Dhaene, K.; Hubner, R.; Kumar-Singh, S.; Weyn, B.; Van Marck, E.

    1998-01-01

    BACKGROUND—Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.
METHODS—Telomerase activity was semi-quantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.
RESULTS—Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.
CONCLUSIONS—Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.

 PMID:10193387

  4. [Soil enzyme activities under two forest types as affected by different levels of nitrogen deposition].

    PubMed

    Zhao, Yu-tao; Li, Xue-feng; Han, Shi-jie; Hu, Yan-ling

    2008-12-01

    A simulation test was conducted to study the change trends of soil cellulase, polyphenol oxidase, and sucrase activities under natural broadleaf-Korean pine (Pinus koraiensis) and secondary poplar (Populus davidiana) -birch (Betula platyphylla) mixed forests as affected by 0, 25, and 50 kg x hm(-2) x a(-1) of N deposition. The results showed that the effects of elevated N deposition on test enzyme activities varied with forest type, and short-term nitrogen addition could significantly affect the test enzyme activities. High N deposition decreased soil polyphyneol oxidase activity, and correspondingly, soil cellulase and sucrase activities also had a trend of decrease.

  5. Do government brochures affect physical activity cognition? A pilot study of Canada's physical activity guide to healthy active living.

    PubMed

    Kliman, Aviva M; Rhodes, Ryan

    2008-08-01

    Health Canada has published national physical activity (PA) guidelines, which are included in their 26-page Physical Activity Guide to Healthy Active Living (CPAG). To date, the use of CPAG as a motivational instrument for PA promotion has not been evaluated. The purpose of this study was to determine whether reading CPAG 1) increased motivational antecedents to engage in regular PA, and 2) increased regular PA intention and behaviour over 1 month. Participants included 130 randomly sampled Canadian adults (18 years or older) who were randomly mailed pack ages consisting of either 1) a questionnaire and a copy of CPAG, or 2) a questionnaire. Questionnaire items pertained to participants' sociodemographics, previous PA behaviours (Godin Leisure-Time Questionnaire) and PA motivation (theory of planned behaviour). Participants were then sent a follow-up questionnaire pertaining to their PA behaviours throughout the previous month. Results revealed significant interactions between the guide condition and previous activity status on instrumental behavioural beliefs about strength activities and subjective norms about endurance activities (p < 0.05), but all other factors were not significantly different. It was concluded that among previously inactive people, receiving this guide may change some informational/motivational constructs, but key motivational antecedents (affective attitude, perceived behavioural control) and outcomes (intention, behaviour) seem unaffected.

  6. Zinc oxide nanoparticles cause inhibition of microbial denitrification by affecting transcriptional regulation and enzyme activity.

    PubMed

    Zheng, Xiong; Su, Yinglong; Chen, Yinguang; Wan, Rui; Liu, Kun; Li, Mu; Yin, Daqiang

    2014-12-02

    Over the past few decades, human activities have accelerated the rates and extents of water eutrophication and global warming through increasing delivery of biologically available nitrogen such as nitrate and large emissions of anthropogenic greenhouse gases. In particular, nitrous oxide (N2O) is one of the most important greenhouse gases, because it has a 300-fold higher global warming potential than carbon dioxide. Microbial denitrification is a major pathway responsible for nitrate removal, and also a dominant source of N2O emissions from terrestrial or aquatic environments. However, whether the release of zinc oxide nanoparticles (ZnO NPs) into the environment affects microbial denitrification is largely unknown. Here we show that the presence of ZnO NPs lead to great increases in nitrate delivery (9.8-fold higher) and N2O emissions (350- and 174-fold higher in the gas and liquid phases, respectively). Our data further reveal that ZnO NPs significantly change the transcriptional regulations of glycolysis and polyhydroxybutyrate synthesis, which causes the decrease in reducing powers available for the reduction of nitrate and N2O. Moreover, ZnO NPs substantially inhibit the gene expressions and catalytic activities of key denitrifying enzymes. These negative effects of ZnO NPs on microbial denitrification finally cause lower nitrate removal and higher N2O emissions, which is likely to exacerbate water eutrophication and global warming.

  7. Catalytic activities of Werner protein are affected by adduction with 4-hydroxy-2-nonenal.

    PubMed

    Czerwińska, Jolanta; Poznański, Jarosław; Dębski, Janusz; Bukowy, Zuzanna; Bohr, Vilhelm A; Tudek, Barbara; Speina, Elżbieta

    2014-01-01

    4-Hydroxy-2-nonenal (HNE) is a reactive α,β-unsaturated aldehyde generated during oxidative stress and subsequent peroxidation of polyunsaturated fatty acids. Here, Werner protein (WRN) was identified as a novel target for modification by HNE. Werner syndrome arises through mutations in the WRN gene that encodes the RecQ DNA helicase which is critical for maintaining genomic stability. This hereditary disease is associated with chromosomal instability, premature aging and cancer predisposition. WRN appears to participate in the cellular response to oxidative stress and cells devoid of WRN display elevated levels of oxidative DNA damage. We demonstrated that helicase/ATPase and exonuclease activities of HNE-modified WRN protein were inhibited both in vitro and in immunocomplexes purified from the cell extracts. Sites of HNE adduction in human WRN were identified at Lys577, Cys727, His1290, Cys1367, Lys1371 and Lys1389. We applied in silico modeling of the helicase and RQC domains of WRN protein with HNE adducted to Lys577 and Cys727 and provided a potential mechanism of the observed deregulation of the protein catalytic activities. In light of the obtained results, we postulate that HNE adduction to WRN is a post-translational modification, which may affect WRN conformational stability and function, contributing to features and diseases associated with premature senescence.

  8. Catalytic activities of Werner protein are affected by adduction with 4-hydroxy-2-nonenal

    PubMed Central

    Czerwińska, Jolanta; Poznański, Jarosław; Dębski, Janusz; Bukowy, Zuzanna; Bohr, Vilhelm A.; Tudek, Barbara; Speina, Elżbieta

    2014-01-01

    4-Hydroxy-2-nonenal (HNE) is a reactive α,β-unsaturated aldehyde generated during oxidative stress and subsequent peroxidation of polyunsaturated fatty acids. Here, Werner protein (WRN) was identified as a novel target for modification by HNE. Werner syndrome arises through mutations in the WRN gene that encodes the RecQ DNA helicase which is critical for maintaining genomic stability. This hereditary disease is associated with chromosomal instability, premature aging and cancer predisposition. WRN appears to participate in the cellular response to oxidative stress and cells devoid of WRN display elevated levels of oxidative DNA damage. We demonstrated that helicase/ATPase and exonuclease activities of HNE-modified WRN protein were inhibited both in vitro and in immunocomplexes purified from the cell extracts. Sites of HNE adduction in human WRN were identified at Lys577, Cys727, His1290, Cys1367, Lys1371 and Lys1389. We applied in silico modeling of the helicase and RQC domains of WRN protein with HNE adducted to Lys577 and Cys727 and provided a potential mechanism of the observed deregulation of the protein catalytic activities. In light of the obtained results, we postulate that HNE adduction to WRN is a post-translational modification, which may affect WRN conformational stability and function, contributing to features and diseases associated with premature senescence. PMID:25170083

  9. Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans.

    PubMed

    Coenen, Volker A; Schlaepfer, Thomas E; Maedler, Burkhard; Panksepp, Jaak

    2011-10-01

    Major depression (MD) might be conceptualized as pathological under-arousal of positive affective systems as parts of a network of brain regions assessing, reconciling and storing emotional stimuli versus an over-arousal of parts of the same network promoting separation-distress/GRIEF. In this context depression can be explained as an emotional pain state that is the result of a disregulation of several sub-systems that under physiological conditions are concerned with bodily or emotional homeostasis of the human organism in a social context. Physiologically, homeostasis is maintained by influences of the SEEKING system represented - amongst others - by the medial forebrain bundle (MFB). Neuroimaging studies show that the MFB has a proven access to the GRIEF/Sadness system. A functional decoupling of these systems with a dysfunctional GRIEF pathway might result in MD. Therewith GRIEF and SEEKING/PLEASURE systems play important roles as opponents in maintenance of emotional homeostasis. Chronic electrical modulation of the reward SEEKING pathways with deep brain stimulation might show anti-depressive effects in humans suffering from MD by re-initiating an emotional equilibrium (of higher or lower activity) between these opposing systems.

  10. Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion.

    PubMed

    Simann, Meike; Schneider, Verena; Le Blanc, Solange; Dotterweich, Julia; Zehe, Viola; Krug, Melanie; Jakob, Franz; Schilling, Tatjana; Schütze, Norbert

    2015-09-01

    Heparins are broadly used for the prevention and treatment of thrombosis and embolism. Yet, osteoporosis is considered to be a severe side effect in up to one third of all patients on long-term treatment. However, the mechanisms underlying this clinical problem are only partially understood. To investigate if heparin affects differentiation of skeletal precursors, we examined the effects of heparin on the osteogenic and adipogenic lineage commitment and differentiation of primary human bone marrow stromal cells (hBMSCs). Due to the known inverse relationship between adipogenesis and osteogenesis and the capacity of pre-differentiated cells to convert into the respective other lineage, we also determined heparin effects on osteogenic conversion and adipogenic differentiation/conversion. Interestingly, heparin did not only significantly increase mRNA expression and enzyme activity of the osteogenic marker alkaline phosphatase (ALP), but it also promoted mineralization during osteogenic differentiation and conversion. Furthermore, the mRNA expression of the osteogenic marker bone morphogenic protein 4 (BMP4) was enhanced. In addition, heparin administration partly prevented adipogenic differentiation and conversion demonstrated by reduced lipid droplet formation along with a decreased expression of adipogenic markers. Moreover, luciferase reporter assays, inhibitor experiments and gene expression analyses revealed that heparin had putative permissive effects on osteogenic signaling via the BMP pathway and reduced the mRNA expression of the Wnt pathway inhibitors dickkopf 1 (DKK1) and sclerostin (SOST). Taken together, our data show a rather supportive than inhibitory effect of heparin on osteogenic hBMSC differentiation and conversion in vitro. Further studies will have to investigate the net effects of heparin administration on bone formation versus bone resorption in vivo to unravel the molecular mechanisms of heparin-associated osteoporosis and reconcile

  11. Donor age of human platelet lysate affects proliferation and differentiation of mesenchymal stem cells.

    PubMed

    Lohmann, Michael; Walenda, Gudrun; Hemeda, Hatim; Joussen, Sylvia; Drescher, Wolf; Jockenhoevel, Stefan; Hutschenreuter, Gabriele; Zenke, Martin; Wagner, Wolfgang

    2012-01-01

    The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1), but it was significantly higher with HPLs from younger donors (<35 years) as compared to older donors (>45 years). Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal). HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1) or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation.

  12. Regional brain activation as a biological marker of affective responsivity to acute exercise: influence of fitness.

    PubMed

    Petruzzello, S J; Hall, E E; Ekkekakis, P

    2001-01-01

    Previous research has shown that regional brain activation, assessed via frontal electroencephalographic (EEG) asymmetry, predicts affective responsivity to aerobic exercise. To replicate and extend this work, in the present study we examined whether resting brain activation was associated with affective responses to an acute bout of aerobic exercise and the extent to which aerobic fitness mediated this relationship. Participants (high-fit, n = 22; low/moderate-fit, n = 45) ran on a treadmill for 30 min at 75% VO2max. EEG and affect were assessed pre- and 0-, 10-, 20-, and 30-min postexercise. Resting EEG asymmetry predicted positive affect (as measured by the energetic arousal subscale of the Activation Deactivation Adjective Check List) postexercise. Furthermore, resting frontal EEG asymmetry predicted affect only in the high-fit group, suggesting the effect might be mediated by some factor related to fitness. It was also shown that subjects with relatively greater left frontal activation had significantly more energy (i.e., activated pleasant affect) following exercise than subjects with relatively greater right frontal activation. In conclusion, aerobic fitness influenced the relationship between resting frontal asymmetry and exercise-related affective responsivity.

  13. Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles

    PubMed Central

    Neyroud, Daria; Cheng, Arthur J.; Bourdillon, Nicolas; Kayser, Bengt; Place, Nicolas; Westerblad, Håkan

    2016-01-01

    The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on–1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on–3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased “voluntary activation.” In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT. PMID:27445844

  14. Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles.

    PubMed

    Neyroud, Daria; Cheng, Arthur J; Bourdillon, Nicolas; Kayser, Bengt; Place, Nicolas; Westerblad, Håkan

    2016-01-01

    The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on-1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on-3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased "voluntary activation." In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT.

  15. Hypoxia Affects Neprilysin Expression Through Caspase Activation and an APP Intracellular Domain-dependent Mechanism

    PubMed Central

    Kerridge, Caroline; Kozlova, Daria I.; Nalivaeva, Natalia N.; Turner, Anthony J.

    2015-01-01

    While gene mutations in the amyloid precursor protein (APP) and the presenilins lead to an accumulation of the amyloid β-peptide (Aβ) in the brain causing neurodegeneration and familial Alzheimer's disease (AD), over 95% of all AD cases are sporadic. Despite the pathologies being indistinguishable, relatively little is known about the mechanisms affecting generation of Aβ in the sporadic cases. Vascular disorders such as ischaemia and stroke are well established risk factors for the development of neurodegenerative diseases and systemic hypoxic episodes have been shown to increase Aβ production and accumulation. We have previously shown that hypoxia causes a significant decrease in the expression of the major Aβ-degrading enzyme neprilysin (NEP) which might deregulate Aβ clearance. Aβ itself is derived from the transmembrane APP along with several other biologically active metabolites including the C-terminal fragment (CTF) termed the APP intracellular domain (AICD), which regulates the expression of NEP and some other genes in neuronal cells. Here we show that in hypoxia there is a significantly increased expression of caspase-3, 8, and 9 in human neuroblastoma NB7 cells, which can degrade AICD. Using chromatin immunoprecipitation we have revealed that there was also a reduction of AICD bound to the NEP promoter region which underlies the decreased expression and activity of the enzyme under hypoxic conditions. Incubation of the cells with a caspase-3 inhibitor Z-DEVD-FMK could rescue the effect of hypoxia on NEP activity protecting the levels of AICD capable of binding the NEP promoter. These data suggest that activation of caspases might play an important role in regulation of NEP levels in the brain under pathological conditions such as hypoxia and ischaemia leading to a deficit of Aβ clearance and increasing the risk of development of AD. PMID:26617481

  16. Regional brain activity and strenuous exercise: predicting affective responses using EEG asymmetry.

    PubMed

    Hall, Eric E; Ekkekakis, Panteleimon; Petruzzello, Steven J

    2007-05-01

    Previous research using the model proposed by Davidson has shown that resting frontal electroencephalographic (EEG) asymmetry can predict affective responses to aerobic exercise at moderate intensities. Specifically, greater relative left frontal activity has been shown to predict positive affect (i.e., energy) following exercise. The purpose of this study was to determine if resting frontal EEG asymmetry would predict affective responses following strenuous exercise. Thirty participants (13 women, 17 men) completed a maximal graded exercise test on a treadmill. EEG was recorded prior to exercise. Affect was measured by the Activation Deactivation Adjective Check List prior to the graded exercise test, immediately following, 10 and 20-min following exercise. Greater relative left frontal activity predicted tiredness and calmness during recovery from exercise, but not tension or energy. Tiredness and calmness following exercise covaried, suggesting that tiredness following exercise might not have been linked with displeasure. These findings offer further support for the link between EEG asymmetry and affective responses to exercise.

  17. Activation of human peroxisome-activated receptor-gamma ...

    EPA Pesticide Factsheets

    Obesity in children has become an epidemic and recent research suggests a possible contribution from exposure to environmental chemicals. Several chemicals, such as phthalates, brominated flame retardants, and perfluorinated chemicals, are common in house dust on floors where children play and are suspected obesogens. Obesogens can act via a mechanism that involves activation of peroxisome proliferator-activated receptor-gamma (PPARy). A previous study found that dust collected from children’s homes binds to PPARy. Here, we investigated the ability of house dust to activate PPARy in a transiently transfected cell assay. Dust samples were collected in 2012 from carpeted and hardwood floors in children’s homes using thimbles fitted into a vacuum cleaner hose (“TEO” samples), or from homes in an adult cohort NIEHS study. Dust was extracted with 50:50 hexane:acetone, sonicated, centrifuged, and the organic layer collected. This was repeated 2X. The extracts were filtered to remove particulates, dried with purified nitrogen, and reconstituted in DMS0 at 200 ug/ul. COS-1 cells were transfected for 24 hrs with a human PPARy vector containing a luciferase reporter, and exposed for 24 hrs to negative controls water or DMSO (0.1%), positive controls Troglitazone (3 uM in water) or Rosiglitazone (100 nM in DMSO), or dust extracts serially diluted in DMEM at 50, 100, and 200 ug/ml in 0.1% DMSO. Cells were lysed and luciferase activity was measured. Data were log-tra

  18. Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability

    SciTech Connect

    Huang, Xiao; Gibson, Lydia M.; Bell, Brittnaie J.; Lovelace, Leslie L.; Pea, Maria Marjorette O.; Berger, Franklin G.; Berger, Sondra H.; Lebioda, Lukasz

    2010-11-03

    Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of {approx}27 amino acids that is not present in bacterial TSs. The extension, which is disordered in all reported crystal structures of TSs, has been considered to play a primary role in protein turnover but not in catalytic activity. In mammalian cells, the variant V3A has a half-life similar to that of wild-type human TS (wt hTS) while V3T is much more stable; V3L, V3F, and V3Y have half-lives approximately half of that for wt hTS. Catalytic turnover rates for most Val3 mutants are only slightly diminished, as expected. However, two mutants, V3L and V3F, have strongly compromised dUMP binding, with K{sub m,app} values increased by factors of 47 and 58, respectively. For V3L, this observation can be explained by stabilization of the inactive conformation of the loop of residues 181-197, which prevents substrate binding. In the crystal structure of V3L, electron density corresponding to a leucine residue is present in a position that stabilizes the loop of residues 181-197 in the inactive conformation. Since this density is not observed in other mutants and all other leucine residues are ordered in this structure, it is likely that this density represents Leu3. In the crystal structure of a V3F {center_dot} FdUMP binary complex, the nucleotide is bound in an alternative mode to that proposed for the catalytic complex, indicating that the high K{sub m,app} value is caused not by stabilization of the inactive conformer but by substrate binding in a nonproductive, inhibitory site. These observations show that the N-terminal extension affects the conformational state of the hTS catalytic region. Each of the mechanisms leading to the high K{sub m,app} values can be exploited to facilitate design of compounds acting as allosteric inhibitors of hTS.

  19. Toward an evolutionary perspective on conceptual representation: species-specific calls activate visual and affective processing systems in the macaque.

    PubMed

    Gil-da-Costa, Ricardo; Braun, Allen; Lopes, Marco; Hauser, Marc D; Carson, Richard E; Herscovitch, Peter; Martin, Alex

    2004-12-14

    Non-human primates produce a diverse repertoire of species-specific calls and have rich conceptual systems. Some of their calls are designed to convey information about concepts such as predators, food, and social relationships, as well as the affective state of the caller. Little is known about the neural architecture of these calls, and much of what we do know is based on single-cell physiology from anesthetized subjects. By using positron emission tomography in awake rhesus macaques, we found that conspecific vocalizations elicited activity in higher-order visual areas, including regions in the temporal lobe associated with the visual perception of object form (TE/TEO) and motion (superior temporal sulcus) and storing visual object information into long-term memory (TE), as well as in limbic (the amygdala and hippocampus) and paralimbic regions (ventromedial prefrontal cortex) associated with the interpretation and memory-encoding of highly salient and affective material. This neural circuitry strongly corresponds to the network shown to support representation of conspecifics and affective information in humans. These findings shed light on the evolutionary precursors of conceptual representation in humans, suggesting that monkeys and humans have a common neural substrate for representing object concepts.

  20. Human-in-the-loop active electrosense.

    PubMed

    Fang, Sandra; Peshkin, Michael; MacIver, Malcolm A

    2016-12-20

    Active electrosense is a non-visual, short range sensing system used by weakly electric fish, enabling such fish to locate and identify objects in total darkness. Here we report initial findings from the use of active electrosense for object localization during underwater teleoperation with a virtual reality (VR) head-mounted display (HMD). The advantage of electrolocating with a VR system is that it naturally allows for aspects of the task that are difficult for a person to perform to be allocated to the computer. However, interpreting weak and incomplete patterns in the incoming data is something that people are typically far better at than computers. To achieve human-computer synergy, we integrated an active electrosense underwater robot with the Oculus Rift HMD. The virtual environment contains a visualization of the electric images of the objects surrounding the robot as well as various virtual fixtures that guide users to regions of higher information value. Initial user testing shows that these fixtures significantly reduce the time taken to localize an object, but may not increase the accuracy of the position estimate. Our results highlight the advantages of translating the unintuitive physics of electrolocation to an intuitive visual representation for accomplishing tasks in environments where imaging systems fail, such as in dark or turbid water.

  1. Active and Passive Commuting to School: Influences on Affect in Primary School Children

    ERIC Educational Resources Information Center

    Hulley, Angela; Bentley, Nick; Clough, Catherine; Fishlock, Adelle; Morrell, Frances; O'Brien, James; Radmore, Joseph

    2008-01-01

    Active commuting among school children is being encouraged for physical and environmental reasons, but little is known about its influence on affect. The aim of this study was to test the hypothesis that children who walk further to school experience increased arousal and affective valence compared with children who walk a short distance. This was…

  2. 75 FR 80114 - Agency Information Collection (Obligation To Report Factors Affecting Entitlement) Activity Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-21

    ... AFFAIRS Agency Information Collection (Obligation To Report Factors Affecting Entitlement) Activity Under... INFORMATION: Title: Obligation to Report Factors Affecting Entitlement (38 CFR 3.204(a)(1), 38 CFR 3.256(a... compensation benefits must report changes in their entitlement factors. Individual factors such as...

  3. Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems

    ERIC Educational Resources Information Center

    Mulder, Martijn J.; Baeyens, Dieter; Davidson, Matthew C.; Casey, B. J.; Van Den Ban, Els; Van Engeland, Herman; Durston, Sarah

    2008-01-01

    The study examines whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. The results conclude that familial vulnerability to ADHD affects activity in both the prefrontal cortex and cerebellum.

  4. Activation of the peripheral endocannabinoid system in human obesity.

    PubMed

    Engeli, Stefan; Böhnke, Jana; Feldpausch, Mareike; Gorzelniak, Kerstin; Janke, Jürgen; Bátkai, Sándor; Pacher, Pál; Harvey-White, Judy; Luft, Friedrich C; Sharma, Arya M; Jordan, Jens

    2005-10-01

    Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.

  5. Situational Motivation and Perceived Intensity: Their Interaction in Predicting Changes in Positive Affect from Physical Activity

    PubMed Central

    Guérin, Eva; Fortier, Michelle S.

    2012-01-01

    There is evidence that affective experiences surrounding physical activity can contribute to the proper self-regulation of an active lifestyle. Motivation toward physical activity, as portrayed by self-determination theory, has been linked to positive affect, as has the intensity of physical activity, especially of a preferred nature. The purpose of this experimental study was to examine the interaction between situational motivation and intensity [i.e., ratings of perceived exertion (RPE)] in predicting changes in positive affect following an acute bout of preferred physical activity, namely, running. Fourty-one female runners engaged in a 30-minute self-paced treadmill run in a laboratory context. Situational motivation for running, pre- and post-running positive affect, and RPE were assessed via validated self-report questionnaires. Hierarchical regression analyses revealed a significant interaction effect between RPE and introjection (P < .05) but not between RPE and identified regulation or intrinsic motivation. At low levels of introjection, the influence of RPE on the change in positive affect was considerable, with higher RPE ratings being associated with greater increases in positive affect. The implications of the findings in light of SDT principles as well as the potential contingencies between the regulations and RPE in predicting positive affect among women are discussed. PMID:22778914

  6. RNASET2 silencing affects miRNAs and target gene expression pattern in a human ovarian cancer cell model.

    PubMed

    Turconi, Giovanna; Scaldaferri, Debora; Fabbri, Marco; Monti, Laura; Lualdi, Marta; Pedrini, Edoardo; Gribaldo, Laura; Taramelli, Roberto; Acquati, Francesco

    2016-12-01

    Ribonucleases (RNases) are hydrolytic enzymes endowed with the ability to either process or degrade ribonucleic acids. Among the many biological functions assigned to RNases, a growing attention has been recently devoted to the control of cancer growth, in the attempt to bring novel therapeutic approaches to clinical oncology. Indeed, several enzymes belonging to different ribonuclease families have been reported in the last decade to display a marked oncosuppressive activity in a wide range of experimental models. The human RNASET2 gene, the only member of the highly conserved T2/Rh/S family of endoribonucleolytic enzymes described in our species, has been shown to display oncosuppressive roles in both in vitro and in vivo models representing several human malignancies. In the present study, we extend previous findings obtained in ovarian cancer models to shed further light on the cell-autonomous roles played by this gene in the context of its oncosuppresive role and to show that RNASET2 silencing can significantly affect the transcriptional output in one of the most thoroughly investigated human ovarian cancer cell lines. Moreover, we report for the first time that RNASET2-mediated changes in the cell transcriptome are in part mediated by its apparent ability to affect the cell's microRNA expression pattern.

  7. [Topographic characteristics of the human electrodermal activity].

    PubMed

    Lazarev, A O

    2014-01-01

    The investigation with participation of 6 test-subjects provided the first evidence that two dermal areas far apart from each other may possess identical spontaneous electrodermal activity (EDA) (r = 0.98) and, on the contrary, adjacent dermal areas may differ in EDA (p = 0.001). Asymmetry in EDA distribution across the human body was demonstrated. Most often the left part of the body was negatively charged relative to the right part. This held true also to the upper body in 59.2% cases and the lower body in 87.3% cases. In the vast majority of cases (98.6-100%) the upper body was charged negatively relative to the lower body.

  8. Structural snapshots of actively translating human ribosomes.

    PubMed

    Behrmann, Elmar; Loerke, Justus; Budkevich, Tatyana V; Yamamoto, Kaori; Schmidt, Andrea; Penczek, Pawel A; Vos, Matthijn R; Bürger, Jörg; Mielke, Thorsten; Scheerer, Patrick; Spahn, Christian M T

    2015-05-07

    Macromolecular machines, such as the ribosome, undergo large-scale conformational changes during their functional cycles. Although their mode of action is often compared to that of mechanical machines, a crucial difference is that, at the molecular dimension, thermodynamic effects dominate functional cycles, with proteins fluctuating stochastically between functional states defined by energetic minima on an energy landscape. Here, we have used cryo-electron microscopy to image ex-vivo-derived human polysomes as a source of actively translating ribosomes. Multiparticle refinement and 3D variability analysis allowed us to visualize a variety of native translation intermediates. Significantly populated states include not only elongation cycle intermediates in pre- and post-translocational states, but also eEF1A-containing decoding and termination/recycling complexes. Focusing on the post-translocational state, we extended this assessment to the single-residue level, uncovering striking details of ribosome-ligand interactions and identifying both static and functionally important dynamic elements.

  9. Phenosafranin inhibits nuclear localization of transglutaminase 2 without affecting its transamidase activity.

    PubMed

    Furutani, Yutaka; Toguchi, Mariko; Shrestha, Rajan; Kojima, Soichi

    2017-03-01

    Transglutaminase 2 (TG2) localizes to the nucleus and induces apoptosis through a crosslinking inactivation of Sp1 in JHH-7 cells treated with acyclic retinoid. We screened an inhibitor suppressing transamidase activity in the nucleus without affecting transamidase activity itself. Phenosafranin was found to inhibit nuclear localization of EGFP-tagged TG2 and dose-dependently reduce nuclear transamidase activity without affecting the activity in a tube. We concluded that phenosafranin was a novel TG2 inhibitor capable of suppressing its nuclear localization.

  10. Imagination in human social cognition, autism, and psychotic-affective conditions.

    PubMed

    Crespi, Bernard; Leach, Emma; Dinsdale, Natalie; Mokkonen, Mikael; Hurd, Peter

    2016-05-01

    Complex human social cognition has evolved in concert with risks for psychiatric disorders. Recently, autism and psychotic-affective conditions (mainly schizophrenia, bipolar disorder, and depression) have been posited as psychological 'opposites' with regard to social-cognitive phenotypes. Imagination, considered as 'forming new ideas, mental images, or concepts', represents a central facet of human social evolution and cognition. Previous studies have documented reduced imagination in autism, and increased imagination in association with psychotic-affective conditions, yet these sets of findings have yet to be considered together, or evaluated in the context of the diametric model. We first review studies of the components, manifestations, and neural correlates of imagination in autism and psychotic-affective conditions. Next, we use data on dimensional autism in healthy populations to test the hypotheses that: (1) imagination represents the facet of autism that best accounts for its strongly male-biased sex ratio, and (2) higher genetic risk of schizophrenia is associated with higher imagination, in accordance with the predictions of the diametric model. The first hypothesis was supported by a systematic review and meta-analysis showing that Imagination exhibits the strongest male bias of all Autism Quotient (AQ) subscales, in non-clinical populations. The second hypothesis was supported, for males, by associations between schizophrenia genetic risk scores, derived from a set of single-nucleotide polymorphisms, and the AQ Imagination subscale. Considered together, these findings indicate that imagination, especially social imagination as embodied in the default mode human brain network, mediates risk and diametric dimensional phenotypes of autism and psychotic-affective conditions.

  11. Walk on the bright side: physical activity and affect in major depressive disorder.

    PubMed

    Mata, Jutta; Thompson, Renee J; Jaeggi, Susanne M; Buschkuehl, Martin; Jonides, John; Gotlib, Ian H

    2012-05-01

    Although prescribed exercise has been found to improve affect and reduce levels of depression, we do not know how self-initiated everyday physical activity influences levels of positive affect (PA) and negative affect (NA) in depressed persons. Fifty-three individuals diagnosed with Major Depressive Disorder (MDD) and 53 never-depressed controls participated in a seven-day experience sampling study. Participants were prompted randomly eight times per day and answered questions about their physical activity and affective state. Over the week, the two groups of participants did not differ in average level of physical activity. As expected, participants with MDD reported lower average PA and higher average NA than did never-depressed controls. Both participants with MDD and controls reported higher levels of PA at prompts after physical activity than at prompts after inactive periods; moreover, for both groups of participants, PA increased from a prompt after an inactive period to a subsequent prompt at which activity was reported. Depressed participants in particular showed a dose-response effect of physical activity on affect: longer duration and/or higher intensity of physical activity increased their PA significantly more than did short duration and/or lower intensity physical activity. Physical activity did not influence NA in either group. In contrast to previous treatment studies that examined the effects of prescribed structured exercise, this investigation showed that self-initiated physical activity influences PA. These findings also underscore the importance of distinguishing between PA and NA to gain a more comprehensive understanding of the effects of physical activity on affect in MDD.

  12. Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood

    PubMed Central

    Llobet, Laura; Toivonen, Janne M.; Montoya, Julio; Ruiz-Pesini, Eduardo; López-Gallardo, Ester

    2015-01-01

    ABSTRACT Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system. The tested concentrations have been previously reported in human blood. Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis. PMID:26398948

  13. Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood.

    PubMed

    Llobet, Laura; Toivonen, Janne M; Montoya, Julio; Ruiz-Pesini, Eduardo; López-Gallardo, Ester

    2015-11-01

    Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system. The tested concentrations have been previously reported in human blood. Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis.

  14. Structural divergence of GPI-80 in activated human neutrophils.

    PubMed

    Nitto, Takeaki; Takeda, Yuji; Yoshitake, Hiroshi; Sendo, Fujiro; Araki, Yoshihiko

    2007-07-27

    GPI-80 is a glycosylphosphatidylinositol (GPI)-anchored protein that is mainly expressed in human neutrophils. Previous studies using 3H9, a monoclonal antibody (mAb) against GPI-80, suggested that GPI-80 regulates leukocyte adherence and migration through Mac-1. GPI-80, which is anchored at the plasma membrane in resting neutrophils, moves into the pseudopodia and is released from activated human neutrophils. Here, we demonstrate that neutrophil activation affects GPI-80 dynamics using a new anti-GPI-80 mAb, designated 4D4, which is directed against the form of GPI-80 found on resting human neutrophils. Similar to 3H9, 4D4 influences Mac-1-dependent neutrophil adhesion. Treatment of purified GPI-80 with periodic acid and trypsin indicated that 3H9 and 4D4 recognize peptide and carbohydrate moieties, respectively. Stimulation with fMLP decreased the binding of 4D4 to GPI-80 on the neutrophil surface but increased the overall expression of GPI-80, as visualized by the 3H9 signal. Confocal laser microscopy revealed the 4D4 signal mainly on cell bodies and at a low level on pseudopodia during migration toward increasing concentrations of fMLP, whereas the 3H9 signal was observed in both areas. In addition, soluble GPI-80 released from activated neutrophils did not bind 4D4. These results suggest that there are two populations of GPI-80 that differ in the ability to bind 4D4. The 4D4-recognized form may regulate Mac-1-dependent neutrophil adhesion, and may subsequently be converted to a 4D4-unrecognized form during neutrophil activation.

  15. Recognition of human activities with wearable sensors

    NASA Astrophysics Data System (ADS)

    He, Weihua; Guo, Yongcai; Gao, Chao; Li, Xinke

    2012-12-01

    A novel approach for recognizing human activities with wearable sensors is investigated in this article. The key techniques of this approach include the generalized discriminant analysis (GDA) and the relevance vector machines (RVM). The feature vectors extracted from the measured signal are processed by GDA, with its dimension remarkably reduced from 350 to 12 while fully maintaining the most discriminative information. The reduced feature vectors are then classified by the RVM technique according to an extended multiclass model, which shows good convergence characteristic. Experimental results on the Wearable Action Recognition Dataset demonstrate that our approach achieves an encouraging recognition rate of 99.2%, true positive rate of 99.18% and false positive rate of 0.07%. Although in most cases, the support vector machines model has more than 70 support vectors, the number of relevance vectors related to different activities is always not more than 4, which implies a great simplicity in the classifier structure. Our approach is expected to have potential in real-time applications or solving problems with large-scale datasets, due to its perfect recognition performance, strong ability in feature reduction, and simple classifier structure.

  16. Ecology of conflict: marine food supply affects human-wildlife interactions on land

    PubMed Central

    Artelle, Kyle A.; Anderson, Sean C.; Reynolds, John D.; Cooper, Andrew B.; Paquet, Paul C.; Darimont, Chris T.

    2016-01-01

    Human-wildlife conflicts impose considerable costs to people and wildlife worldwide. Most research focuses on proximate causes, offering limited generalizable understanding of ultimate drivers. We tested three competing hypotheses (problem individuals, regional population saturation, limited food supply) that relate to underlying processes of human-grizzly bear (Ursus arctos horribilis) conflict, using data from British Columbia, Canada, between 1960–2014. We found most support for the limited food supply hypothesis: in bear populations that feed on spawning salmon (Oncorhynchus spp.), the annual number of bears/km2 killed due to conflicts with humans increased by an average of 20% (6–32% [95% CI]) for each 50% decrease in annual salmon biomass. Furthermore, we found that across all bear populations (with or without access to salmon), 81% of attacks on humans and 82% of conflict kills occurred after the approximate onset of hyperphagia (July 1st), a period of intense caloric demand. Contrary to practices by many management agencies, conflict frequency was not reduced by hunting or removal of problem individuals. Our finding that a marine resource affects terrestrial conflict suggests that evidence-based policy for reducing harm to wildlife and humans requires not only insight into ultimate drivers of conflict, but also management that spans ecosystem and jurisdictional boundaries. PMID:27185189

  17. Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects.

    PubMed

    Kriesel, John D; Bhatia, Amiteshwar; Thomas, Alun

    2014-01-01

    Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. We present here a genotype-phenotype analysis of CSSG-1 in a new, unrelated human population. Seven hundred fifty-eight human subjects were enrolled in a case/control Cold Sore Study. CSSG-1 genotyping, herpes simplex virus 1 (HSV1) serotyping, demographic and phenotypic data was available from 622 analyzed subjects. Six major alleles (H1-H6) were tested for associations with each of the self-reported phenotypes. The statistical analysis was adjusted for age, sex and ethnicity. Genotype-phenotype associations were analyzed from 388 HSV1-seropositive subjects. There were significant CSSG-1 haplotype effects on annual cold sore outbreaks (P=0.006), lifetime cold sores (P=0.012) and perceived cold sore severity (P=0.012). There were relatively consistent trends toward protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2, and H4 haplotypes tended to have more frequent and more severe episodes. Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study.

  18. Triclosan and bisphenol a affect decidualization of human endometrial stromal cells.

    PubMed

    Forte, Maurizio; Mita, Luigi; Cobellis, Luigi; Merafina, Verdiana; Specchio, Raffaella; Rossi, Sergio; Mita, Damiano Gustavo; Mosca, Lavinia; Castaldi, Maria Antonietta; De Falco, Maria; Laforgia, Vincenza; Crispi, Stefania

    2016-02-15

    In recent years, impaired fertility and endometrium related diseases are increased. Many evidences suggest that environmental pollution might be considered a risk factor for endometrial physiopathology. Among environmental pollutants, endocrine disrupting chemicals (EDCs) act on endocrine system, causing hormonal imbalance which, in turn, leads to female and male reproductive dysfunctions. In this work, we studied the effects of triclosan (TCL) and bisphenol A (BPA), two widespread EDCs, on human endometrial stromal cells (ESCs), derived from endometrial biopsies from woman not affected by endometriosis. Cell proliferation, cell cycle, migration and decidualization mechanisms were investigated. Treatments have been performed with both the EDCs separately or in presence and in absence of progesterone used as decidualization stimulus. Both TCL and BPA did not affect cell proliferation, but they arrested ESCs at G2/M phase of cell cycle enhancing cell migration. TCL and BPA also increased gene expression and protein levels of some decidualization markers, such as insulin growth factor binding protein 1 (IGFBP1) and prolactin (PRL), amplifying the effect of progesterone alone. All together, our data strongly suggest that TCL and BPA might alter human endometrium physiology so affecting fertility and pregnancy outcome.

  19. The Voice of Emotion across Species: How Do Human Listeners Recognize Animals' Affective States?

    PubMed Central

    Scheumann, Marina; Hasting, Anna S.; Kotz, Sonja A.; Zimmermann, Elke

    2014-01-01

    Voice-induced cross-taxa emotional recognition is the ability to understand the emotional state of another species based on its voice. In the past, induced affective states, experience-dependent higher cognitive processes or cross-taxa universal acoustic coding and processing mechanisms have been discussed to underlie this ability in humans. The present study sets out to distinguish the influence of familiarity and phylogeny on voice-induced cross-taxa emotional perception in humans. For the first time, two perspectives are taken into account: the self- (i.e. emotional valence induced in the listener) versus the others-perspective (i.e. correct recognition of the emotional valence of the recording context). Twenty-eight male participants listened to 192 vocalizations of four different species (human infant, dog, chimpanzee and tree shrew). Stimuli were recorded either in an agonistic (negative emotional valence) or affiliative (positive emotional valence) context. Participants rated the emotional valence of the stimuli adopting self- and others-perspective by using a 5-point version of the Self-Assessment Manikin (SAM). Familiarity was assessed based on subjective rating, objective labelling of the respective stimuli and interaction time with the respective species. Participants reliably recognized the emotional valence of human voices, whereas the results for animal voices were mixed. The correct classification of animal voices depended on the listener's familiarity with the species and the call type/recording context, whereas there was less influence of induced emotional states and phylogeny. Our results provide first evidence that explicit voice-induced cross-taxa emotional recognition in humans is shaped more by experience-dependent cognitive mechanisms than by induced affective states or cross-taxa universal acoustic coding and processing mechanisms. PMID:24621604

  20. Inference of human affective states from psychophysiological measurements extracted under ecologically valid conditions

    PubMed Central

    Betella, Alberto; Zucca, Riccardo; Cetnarski, Ryszard; Greco, Alberto; Lanatà, Antonio; Mazzei, Daniele; Tognetti, Alessandro; Arsiwalla, Xerxes D.; Omedas, Pedro; De Rossi, Danilo; Verschure, Paul F. M. J.

    2014-01-01

    Compared to standard laboratory protocols, the measurement of psychophysiological signals in real world experiments poses technical and methodological challenges due to external factors that cannot be directly controlled. To address this problem, we propose a hybrid approach based on an immersive and human accessible space called the eXperience Induction Machine (XIM), that incorporates the advantages of a laboratory within a life-like setting. The XIM integrates unobtrusive wearable sensors for the acquisition of psychophysiological signals suitable for ambulatory emotion research. In this paper, we present results from two different studies conducted to validate the XIM as a general-purpose sensing infrastructure for the study of human affective states under ecologically valid conditions. In the first investigation, we recorded and classified signals from subjects exposed to pictorial stimuli corresponding to a range of arousal levels, while they were free to walk and gesticulate. In the second study, we designed an experiment that follows the classical conditioning paradigm, a well-known procedure in the behavioral sciences, with the additional feature that participants were free to move in the physical space, as opposed to similar studies measuring physiological signals in constrained laboratory settings. Our results indicate that, by using our sensing infrastructure, it is indeed possible to infer human event-elicited affective states through measurements of psychophysiological signals under ecological conditions. PMID:25309310

  1. Looking at human eyes affects contralesional stimulus processing after right hemispheric stroke.

    PubMed

    Maravita, A; Posteraro, L; Husain, M; Vuilleumier, P; Schwartz, S; Driver, J

    2007-10-16

    Human eyes are a powerful social cue that may automatically attract the attention of an observer. Here we tested whether looking toward open human eyes, as often arises in standard clinical "confrontation" tests, may affect contralesional errors in a group of right brain-damaged patients showing visual extinction. Patients were requested to discriminate peripheral shape-targets presented on the left, right, or bilaterally. On each trial they also saw a central task-irrelevant stimulus, comprising an image of the eye sector of a human face, with those seen eyes open or closed. The conditions with central eye stimuli open (vs closed) induced more errors for contralesional peripheral targets, particularly for bilateral trials. These results suggest that seeing open eyes in central vision may attract attentional resources there, reducing attention to the periphery, particularly for the affected contralesional side. The seen gaze of the examiner may thus need to be considered during confrontation testing and may contribute to the effectiveness of that clinical procedure.

  2. Assessment of heavy metal pollution risks in Yonki Reservoir environmental matrices affected by gold mining activity.

    PubMed

    Kapia, Samuel; Rao, B K Rajashekhar; Sakulas, Harry

    2016-10-01

    This study reports the heavy metal (Hg, Cd, Cr, Cu, and Pb) contamination risks to and safety of two species of fresh water fish (tilapia, Oreochromis mossambicus and carp, Cyprinus carpio) that are farmed in the Yonki Reservoir in the Eastern Highlands of Papua New Guinea (PNG). The upper reaches of the reservoir are affected by alluvial and large-scale gold mining activities. We also assessed heavy metal levels in the surface waters and sediments and in selected aquatic plant species from the reservoir and streams that intersect the gold mining areas. The water quality was acceptable, except for the Cr concentration, which exceeded the World Health Organization (WHO) standard for water contamination. The sediments were contaminated with Cd and Cu in most of the sampling stations along the upstream waters and the reservoir. The Cd concentration in the sediments exceeded the US Environmental Protection Agency's Sediment Quality Guideline (SQG) values, and the geoaccumulation index (Igeo) values indicated heavy to extreme pollution. In addition, the Cd, Cu, and Pb concentrations in aquatic plants exceeded the WHO guidelines for these contaminants. Between the fish species, tilapia accumulated significantly higher (P < 0.05) Cu in their organ tissues than carp, confirming the bioaccumulation of some metals in the aquatic fauna. The edible muscles of the fish specimens had metal concentrations below the maximum permissible levels established by statutory guidelines. In addition, a human health risk assessment, performed using the estimated weekly intake (EWI) values, indicated that farmed fish from the Yonki Reservoir are safe for human consumption.

  3. Activity of erdosteine on mucociliary transport in patients affected by chronic bronchitis.

    PubMed

    Olivieri, D; Del Donno, M; Casalini, A; D'Ippolito, R; Fregnan, G B

    1991-01-01

    The influence of erdosteine (a mucomodulator endowed with mucolytic and antioxidant properties) on human mucociliary transport (MCT) was investigated in a double-blind placebo controlled study. Sixteen former smokers affected by chronic bronchitis, preselected for their mucociliary responsiveness to an inhaled beta 2-agonist, were divided into two groups (matched by number, sex, age and FEV1%) and orally treated with placebo or erdosteine (300 mg t.i.d.) for 8 days. Their MCT was assessed by the bronchofiberscopy technique just before starting the treatment and at the end of the treatment. The pretreatment mucus transport velocity in these patients was significantly decreased with respect to healthy subjects. The erdosteine treatment induced a significant improvement of MCT while placebo was inactive (mean % variation +/- SE against their baseline values being +60.4 +/- 18.4 and -3.0 +/- 5.9, respectively). This peculiar activity of erdosteine on mucus transport may be of clinical usefulness in chronic bronchitic patients and it can be added to beta 2-agonist to restore the decreased MCT.

  4. Oligomeric state affects oxygen dissociation and diguanylate cyclase activity of globin coupled sensors.

    PubMed

    Burns, Justin L; Deer, D Douglas; Weinert, Emily E

    2014-11-01

    Bacterial biofilm formation is regulated by enzymes, such as diguanylate cyclases, that respond to environmental signals and alter c-di-GMP levels. Diguanylate cyclase activity of two globin coupled sensors is shown to be regulated by gaseous ligands, with cyclase activity and O2 dissociation affected by protein oligomeric state.

  5. Neural Activation Underlying Cognitive Control in the Context of Neutral and Affectively Charged Pictures in Children

    ERIC Educational Resources Information Center

    Lamm, Connie; White, Lauren K.; McDermott, Jennifer Martin; Fox, Nathan A.

    2012-01-01

    The neural correlates of cognitive control for typically developing 9-year-old children were examined using dense-array ERPs and estimates of cortical activation (LORETA) during a go/no-go task with two conditions: a neutral picture condition and an affectively charged picture condition. Activation was estimated for the entire cortex after which…

  6. How Does Domain Replacement Affect Fibril Formation of the Rabbit/Human Prion Proteins

    PubMed Central

    Yan, Xu; Huang, Jun-Jie; Zhou, Zheng; Chen, Jie; Liang, Yi

    2014-01-01

    Background It is known that in vivo human prion protein (PrP) have the tendency to form fibril deposits and are associated with infectious fatal prion diseases, while the rabbit PrP does not readily form fibrils and is unlikely to cause prion diseases. Although we have previously demonstrated that amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and macromolecular crowding has different effects on fibril formation of the rabbit/human PrPs, we do not know which domains of PrPs cause such differences. In this study, we have constructed two PrP chimeras, rabbit chimera and human chimera, and investigated how domain replacement affects fibril formation of the rabbit/human PrPs. Methodology/Principal Findings As revealed by thioflavin T binding assays and Sarkosyl-soluble SDS-PAGE, the presence of a strong crowding agent dramatically promotes fibril formation of both chimeras. As evidenced by circular dichroism, Fourier transform infrared spectroscopy, and proteinase K digestion assays, amyloid fibrils formed by human chimera have secondary structures and proteinase K-resistant features similar to those formed by the human PrP. However, amyloid fibrils formed by rabbit chimera have proteinase K-resistant features and secondary structures in crowded physiological environments different from those formed by the rabbit PrP, and secondary structures in dilute solutions similar to the rabbit PrP. The results from transmission electron microscopy show that macromolecular crowding caused human chimera but not rabbit chimera to form short fibrils and non-fibrillar particles. Conclusions/Significance We demonstrate for the first time that the domains beyond PrP-H2H3 (β-strand 1, α-helix 1, and β-strand 2) have a remarkable effect on fibrillization of the rabbit PrP but almost no effect on the human PrP. Our findings can help to explain why amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary

  7. Foods and food constituents that affect the brain and human behavior

    NASA Technical Reports Server (NTRS)

    Lieberman, Harris R.; Wurtman, Richard J.

    1986-01-01

    Until recently, it was generally believed that brain function was usually independent of day-to-day metabolic changes associated with consumption of food. Although it was acknowledged that peripheral metabolic changes associated with hunger or satiety might affect brain function, other effects of foods on the brain were considered unlikely. However, in 1971, Fernstrom and Wurtman discovered that under certain conditions, the protein-to-carbohydrate ratio of a meal could affect the concentration of a particular brain neurotransmitter. That neurotransmitter, serotonin, participates in the regulation of a variety of central nervous system (CNS) functions including sleep, pain sensitivity, aggression, and patterns of nutrient selection. The activity of other neurotransmitter systems has also been shown to be, under certain conditions, affected by dietary constituents which are given either as ordinary foods or in purified form. For example, the CNS turnover of two catecholamine neurotransmitters, dopamine and norepinephrine, can be altered by ingestion of their amino acid precursor, tyrosine, when neurons that release these monoamines are firing frequently. Similarly, lecithin, a dietary source of choline, and choline itself have been shown to increase the synthesis of acetylcholine when cholinergic neurons are very active. It is possible that other neurotransmitters could also be affected by precursor availability or other, as yet undiscovered peripheral factors governed by food consumption. The effects of food on neurotransmitters and behavior are discussed.

  8. Human Activity and Pollution in Antarctica

    NASA Astrophysics Data System (ADS)

    Graf, H.-F.; Shirsat, S. V.; Podzun, R.

    2009-04-01

    A regional climate chemistry model is used to determine the level of pollution of the Antarctic continent due to anthropogenic and natural emission of sulphur species. Based on an emission inventory for the year 2004/2005 including emissions from energy use and ground traffic at and between Antarctic research stations, flight activity, tourist and scientific ship operations, and emissions from the Mt. Erebus volcano, atmospheric concentration and deposition rates of sulphur species and black carbon were simulated at 0.5 degree resolution for the whole Antarctic continent. The biggest anthropogenic source of pollution is ship operations. These concentrate near the Antarctic Peninsula and close to the big scientific stations at Queen Maud Land and in the Ross sea area. The prevailing winds guarantee that most of the anthropogenic emissions from sources near the coast will be blown to lower latitudes and do not affect the continent. While atmospheric concentrations over vast areas remain extremely low, in some places locally concentrations and deposition rates are reached that may be detectable by in-situ measurements and give rise to concern. Especially at the Peninsula atmospheric concentrations and surface deposition of sulphur and soot are dominated by ship emissions. The largest part of shipping activity in this region is from tourist ships, a strongly increasing business. The by far biggest source of sulphur species in Antarctica is the Mt. Erebus volcano. It is also the only source that remains equally strong in polar winter. However, due to its high altitude and the long life time of SO2, especially in winter resulting in long range transport and dilution, Erebus emissions contribute relatively little to deposition of sulphur in the most anthropogenic polluted areas while they dominate the sulphur deposition in central Antarctica.

  9. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1-60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  10. Derivation of Huntington disease affected Genea020 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Peura, Teija; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1.43 and demonstrated alkaline phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  11. Derivation of Huntington Disease affected Genea018 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea018 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 46 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 75% of cells expressed Nanog, 91% Oct4, 73% Tra1-60 and 96% SSEA4, gave a Pluritest pluripotency score of 31.12, Novelty of 1.45, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.

  12. Activated platelets signal chemokine synthesis by human monocytes.

    PubMed Central

    Weyrich, A S; Elstad, M R; McEver, R P; McIntyre, T M; Moore, K L; Morrissey, J H; Prescott, S M; Zimmerman, G A

    1996-01-01

    Human blood monocytes adhere rapidly and for prolonged periods to activated platelets that display P-selectin, an adhesion protein that recognizes a specific ligand on leukocytes, P-selectin glycoprotein-1. We previously demonstrated that P-selectin regulates expression and secretion of cytokines by stimulated monocytes when it is presented in a purified, immobilized form or by transfected cells. Here we show that thrombin-activated platelets induce the expression and secretion of monocyte chemotactic protein-1 and IL-8 by monocytes. Enhanced monokine synthesis requires engagement of P-selectin glycoprotein-1 on the leukocyte by P-selectin on the platelet. Secretion of the chemokines is not, however, directly signaled by P-selectin; instead, tethering of the monocytes by P-selectin is required for their activation by RANTES (regulated upon activation normal T cell expressed presumed secreted), a platelet chemokine not previously known to induce immediate-early gene products in monocytes. Adhesion of monocytes to activated platelets results in nuclear translocation of p65 (RelA), a component of the NF-kappaB family of transcription factors that binds kappaB sequences in the regulatory regions of monocyte chemotactic protein-1, IL-8, and other immediate-early genes. However, expression of tissue factor, a coagulation protein that also has a kappaB sequence in the 5' regulatory region of its gene, is not induced in monocytes adherent to activated platelets. Thus, contact of monocytes with activated platelets differentially affects the expression of monocyte products. These experiments suggest that activated platelets regulate chemokine secretion by monocytes in inflammatory lesions in vivo and provide a model for the study of gene regulation in cell-cell interactions. PMID:8617886

  13. Decavanadate inhibits the cell-free activation of neutrophil NADPH oxidase without affecting tyrosine phosphorylation.

    PubMed

    Okamura, N; Sakai, T; Nishimura, Y; Sakai, M; Araki, S; Yamaguchi, M; Ishibashi, S

    1999-08-01

    NADPH oxidase was activated by arachidonate in a cell-free system consisting of membrane and cytosol fractions prepared from guinea pig neutrophils. Vanadate apparently inhibited the NADPH oxidase activity in the cell-free system (IC50=2 microM) without phosphotyrosine accumulation. The pH dependency and stability of the inhibitory effect observed for vanadate solution indicated that decavanadate, an isopolyanion of vanadate, was responsible for the inhibition. Pervanadate (vanadyl hydroperoxide) also inhibited the oxidase activity but at a higher concentration (IC50=0.2 mM). Decavanadate lowered the Vmax but did not affect the Km value of NADPH oxidase for NADPH. Decavanadate inhibited the activation process of NADPH oxidase but not the oxidase activity itself. Decavanadate-pretreatment of membrane and cytosol fractions irreversibly decreased the abilities of both fractions to activate NADPH oxidase in the cell-free system. Translocation of p47-phox, one of the cytosolic activation factors of NADPH oxidase, from cytosol to membrane, was little affected by decavanadate. These results suggest that decavanadate inhibits the activation of NADPH oxidase in the cell-free system without affecting the phosphotyrosine phosphatase, and that decavanadate can bind to both the membrane and cytosolic activation factors when they are in a dormant state, but not to the active oxidase complex.

  14. Is spinal excitability of the triceps surae mainly affected by muscle activity or body position?

    PubMed

    Cattagni, T; Martin, A; Scaglioni, G

    2014-06-15

    The aim of this study was to determine how muscle activity and body orientation contribute to the triceps surae spinal transmission modulation, when moving from a sitting to a standing position. Maximal Hoffmann-reflex (Hmax) and motor potential (Mmax) were evoked in the soleus (SOL), medial and lateral gastrocnemius in 10 male subjects and in three conditions, passive sitting, active sitting and upright standing, with the same SOL activity in active sitting and upright standing. Moreover volitional wave (V) was evoked in the two active conditions (i.e., active sitting and upright standing). The results showed that SOL Hmax/Mmax was lower in active sitting than in passive sitting, while for the gastrocnemii it was not significantly altered. For the three plantar flexors, Hmax/Mmax was lower in upright standing than in active sitting, whereas V/Mmax was not modulated. SOL H-reflex is therefore affected by the increase in muscle activity and change in body orientation, while, in the gastrocnemii, it was only affected by a change in posture. In conclusion, passing from a sitting to a standing position affects the Hmax/Mmax of the whole triceps surae, but the mechanisms responsible for this change differ among the synergist muscles. The V/Mmax does not change when upright stance is assumed. This means that the increased inhibitory activity in orthostatic position is compensated by an increased excitatory inflow to the α-motoneurons of central and/or peripheral origin.

  15. A critique and empirical assessment of Alexandra Horowitz and Julie Hecht's "Examining dog-human play: the characteristics, affect, and vocalizations of a unique interspecific interaction".

    PubMed

    Mitchell, Robert W

    2017-02-08

    Horowitz and Hecht (Anim Cog 19:779-788, 2016) presented data about activities and vocalizations during brief videotaped dog-owner play provided by owners, examined these in relation to human affect during play, and made comparisons from their results to other research on activities and vocalizations during dog-human play. In this critique, I describe problems with Horowitz and Hecht's methodology, analyses, and evidence; in their interpretations of the data, evidence, and categorizations provided in other research, particularly my own studies of dog-human play; and in their claims of novelty for their findings. I argue that, to support their ideas about vocalizations and play types during dog-human play and their comparisons to other studies, their study requires fuller descriptions and reliability for their coding of vocalizations and play types, appropriate statistical analyses, and accurate descriptions of prior research. I also argue that their methodology provides results strikingly similar in many aspects to those of other researchers studying dog-human play, contrary to their claims of novel findings. Finally, I examine their suggestions about relationships between human affect and types of play activities and vocalizations using the videos of dog-human play I discussed in earlier publications, discovering minimal, if any, relationship.

  16. Health in the hot zone - How could global warming affect humans?

    SciTech Connect

    Monastersky, R.

    1996-04-06

    A soon-to-be-released report from the World Health Organization examines the health effects of global warming, calling climate change one of the largest public health challenges for the upcoming century. The issue extends beyond tropical illness: deaths caused directly by heat, dwindling agricultural yields etc. could all affect human health. This article looks at the following health related effects and gives an overview of the scientific information available on each: temperature and mortality; tropical trouble, including vecorborne diseases and increase in susceptable populations; and waterborne problems such as cholera, harmful algal bloomes, food shortages.

  17. Does correlated color temperature affect the ability of humans to identify veins?

    PubMed

    Argyraki, Aikaterini; Clemmensen, Line Katrine Harder; Petersen, Paul Michael

    2016-01-01

    In the present study we provide empirical evidence and demonstrate statistically that white illumination settings can affect the human ability to identify veins in the inner hand vasculature. A special light-emitting diode lamp with high color rendering index (CRI 84-95) was developed and the effect of correlated color temperature was evaluated, in the range between 2600 and 5700 K at an illuminance of 40±9  lx on the ability of adult humans to identify veins. It is shown that the ability to identify veins can, on average, be increased up to 24% when white illumination settings that do not resemble incandescent light are applied. The illuminance reported together with the effect of white illumination settings on direct visual perception of biosamples are relevant for clinical investigations during the night.

  18. Cognition and affective style: Individual differences in brain electrical activity during spatial and verbal tasks.

    PubMed

    Bell, Martha Ann; Fox, Nathan A

    2003-12-01

    Relations between brain electrical activity and performance on two cognitive tasks were examined in a normal population selected to be high on self-reported measures of Positive or Negative Affectivity. Twenty-five right-handed women, from an original pool of 308 college undergraduates, were the participants. EEG was recorded during baseline and during psychometrically matched spatial and verbal tasks. As predicted, participants who were high in Positive Affectivity performed equally well on the verbal and spatial tasks, while participants who were high in Negative Affectivity had spatial scores that were lower than their verbal scores. There were no group differences in baseline EEG. Both groups exhibited left central activation (i.e., alpha suppression) during the verbal and spatial tasks. When EEG data were analyzed separately for the group high in Positive Affectivity, there was evidence of parietal activation for the spatial task relative to the verbal task. The EEG data for the group high in Negative Affectivity had comparable EEG power values during verbal and spatial tasks at parietal scalp locations. These data suggest that, within a selected normal population, differences in affective style may interact with cognitive performance and with the brain electrical activity associated with that performance.

  19. Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure

    NASA Astrophysics Data System (ADS)

    Laakso, Ilkka; Hirata, Akimasa

    2011-12-01

    Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core-temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters—some of which may be subject to considerable uncertainty—that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body-core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg-1.

  20. Hypericum perforatum differentially affects corticosteroid receptor-mRNA expression in human monocytic U-937 cells.

    PubMed

    Enning, F; Murck, H; Krieg, J-C; Vedder, H

    2011-09-01

    A dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis represents a prominent finding in major depression, possibly related to a dysfunction of the corticosteroid receptor system. Antidepressants are involved in the restoration of the altered feed-back mechanism of the HPA-axis, probably via normalization of corticosteroid receptor functions. Since Hypericum perforatum has antidepressive properties, we here examined its putative actions on glucocorticosteroid receptor mRNA levels in human blood cells as a peripheral model for neuroendocrine effects in human brain cells. Our data show that Hypericum (LI 160) affects the cellular mRNA levels of both, the glucocorticoid receptor (GR)-α and its inhibitory counterpart, the GR-β, at clinically-relevant concentrations. Under these conditions, a bimodal effect was observed. Dose-response studies suggest a rather small effective concentration range and time-effect data show a primary and transient up-regulation of GR-α mRNA levels and a down-regulation of GR-β mRNA levels after 16 h of treatment. The sodium channel blocker benzamil neutralized the effects of Hypericum, pointing to an at least partial mechanism of action via this pathway. In conclusion, Hypericum treatment differentially affects GR-mRNA levels in the human system. Our data suggest a bimodal effect on GR, resulting in a time-and dose-related modification of GR-mediated cellular effects. Such a mechanism has been alleged as an important way of action for a number of antidepressants. It is the first time that a specific effect on both receptors, especially on the subtype of GR-β, is shown under antidepressive treatment in a human system under in vitro conditions.

  1. Cigarette smoke extract affects functional activity of MRP1 in bronchial epithelial cells.

    PubMed

    van der Deen, Margaretha; de Vries, Elisabeth G E; Visserman, Hylke; Zandbergen, Wouter; Postma, Dirkje S; Timens, Wim; Timmer-Bosscha, Hetty

    2007-01-01

    Cigarette smoke is the principal risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is a member of the ATP-binding cassette (ABC) superfamily of transporters, which transport physiologic and toxic substrates across cell membranes. MRP1 is highly expressed in lung epithelium. This study aims to analyze the effect of cigarette smoke extract (CSE) on MRP1 activity. In the human bronchial epithelial cell line 16HBE14o-, MRP1 function was studied flow cytometrically by cellular retention of carboxyfluorescein (CF) after CSE incubation and MRP1 downregulation by RNA interference (siRNA). Cell survival was measured by the MTT assay. Immunocytochemically, it was shown that 16HBE14o(-) expressed MRP1 and breast cancer resistance protein. Coincubation of CSE IC50 (1.53% +/- 0.22%) with MK571 further decreased cell survival 31% (p, = 0.018). CSE increased cellular CF retention dose dependently from 1.7-fold at 5% CSE to 10.3-fold at 40% CSE (both p < 0.05). siRNA reduced MRP1 RNA expression with 49% and increased CF accumulation 67% versus control transfected cells. CSE exposure further increased CF retention 24% (p = 0.031). A linear positive relation between MRP1 function and CSE-modulating effects (r = 0.99, p =0.089) was shown in untransfected, control transfected, and MRP1 downregulated 16HBE14o- cells analogous to blocking effects with MRP1 inhibitor MK571 (r = 0.99, p = 0.034). In conclusion, cigarette smoke extract affects MRP1 activity probably competitively in bronchial epithelial cells. Inhibition of MRP1 in turn results in higher CSE toxicity. We propose that MRP1 may be a protective protein for COPD development.

  2. Blastocystis: how do specific diets and human gut microbiota affect its development and pathogenicity?

    PubMed

    Lepczyńska, M; Białkowska, J; Dzika, E; Piskorz-Ogórek, K; Korycińska, J

    2017-03-22

    Blastocystis is an enteric parasite that inhabits the gastrointestinal tract of humans and many animals. This emerging parasite has a worldwide distribution. It is often identified as the most common eukaryotic organism reported in human fecal samples. This parasite is recognized and diagnosed more often than ever before. Furthermore, some strains develop resistance against currently recommended drugs, such as metronidazole; therefore, the use of natural remedies or special diets has many positive aspects that may address this problem. The goal of this review is to compare natural treatments and various diets against the efficacy of drugs, and describe their influence on the composition of the gut microbiota, which affects Blastocystis growth and the occurrence of symptoms. This article reviews important work in the literature, including the classification, life cycle, epidemiology, pathogenesis, pathogenicity, genetics, biology, and treatment of Blastocystis. It also includes a review of the current knowledge about human gut microbiota and various diets proposed for Blastocystis eradication. The literature has revealed that garlic, ginger, some medical plants, and many spices contain the most effective organic compounds for parasite eradication. They work by inhibiting parasitic enzymes and nucleic acids, as well as by inhibiting protein synthesis. The efficacy of any specific organic compound depends on the Blastocystis subtype, and, consequently, on its immunity to treatment. In conclusion, the article discusses the findings that human gut microbiota composition triggers important mechanisms at the molecular level, and, thus, has a crucial influence on the parasitic pathogenicity.

  3. Uptake and intracellular activity of fluconazole in human polymorphonuclear leukocytes.

    PubMed Central

    Pascual, A; García, I; Conejo, C; Perea, E J

    1993-01-01

    The penetration of fluconazole into human polymorphonuclear leukocytes (PMNs) and tissue culture epithelial cells (McCoy) was evaluated. At different extracellular concentrations (0.5 to 10 mg/liter), fluconazole reached cell-associated concentrations greater than the extracellular ones in either human PMNs (intracellular concentration to extracellular concentration ratio, > or = 2.2) or McCoy cells (intracellular concentration to extracellular concentration ratio, > or = 1.3). The uptake of fluconazole by PMNs was rapid and reversible but was not energy dependent. The intracellular penetration of fluconazole was not affected by environmental pH or temperature. Ingestion of opsonized zymosan and opsonized Candida albicans did not significantly increase the amount of PMN-associated fluconazole. At therapeutic extracellular concentrations, the intracellular activity of fluconazole against C. albicans in PMNs was significantly lower than that of amphotericin B. It was concluded that fluconazole reaches high intracellular concentrations within PMNs but shows moderate activity against intracellular C. albicans in vitro. PMID:8452347

  4. Increased proteasome activity determines human embryonic stem cell identity

    PubMed Central

    Vilchez, David; Boyer, Leah; Morantte, Ianessa; Lutz, Margaret; Merkwirth, Carsten; Joyce, Derek; Spencer, Brian; Page, Lesley; Masliah, Eliezer; Berggren, W. Travis; Gage, Fred H.; Dillin, Andrew

    2016-01-01

    Embryonic stem cells are able to replicate continuously in the absence of senescence and, therefore, are immortal in culture1,2. While genome stability is central for survival of stem cells; proteome stability may play an equally important role in stem cell identity and function. Additionally, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. We hypothesized that stem cells have an increased proteostasis ability compared to their differentiated counterparts and asked whether proteasome activity differed among human embryonic stem cells (hESCs). Notably, hESC populations exhibit a high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11/RPN-63–5 and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. Proteasome inhibition affects pluripotency of hESCs inducing differentiation towards specific cell lineages. FOXO4, an insulin/IGF-1 responsive transcription factor associated with long lifespan in invertebrates6,7, regulates proteasome activity by modulating the expression of PSMD11 in hESCs. Our results establish a novel regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates with hESC function and identity. PMID:22972301

  5. Effects of butyltins on mitogen-activated-protein kinase kinase kinase and Ras activity in human natural killer cells.

    PubMed

    Celada, Lindsay J; Whalen, Margaret M

    2014-09-01

    Butyltins (BTs) contaminate the environment and are found in human blood. BTs, tributyltin (TBT) and dibutyltin (DBT) diminish the cytotoxic function and levels of key proteins of human natural killer (NK) cells. NK cells are an initial immune defense against tumors, virally infected cells and antibody-coated cells and thus critical to human health. The signaling pathways that regulate NK cell functions include mitogen-activated protein kinases (MAPKs). Studies have shown that exposure to BTs leads to activation of specific MAPKs and MAPK kinases (MAP2Ks) in human NK cells. MAP2K kinases (MAP3Ks) are upstream activators of MAP2Ks, which then activate MAPKs. The current study examined if BT-induced activation of MAP3Ks was responsible for MAP2K and thus, MAPK activation. This study examines the effects of TBT and DBT on the total levels of two MAP3Ks, c-Raf and ASK1, as well as activating and inhibitory phosphorylation sites on these MAP3Ks. In addition, the immediate upstream activator of c-Raf, Ras, was examined for BT-induced alterations. Our results show significant activation of the MAP3K, c-Raf, in human NK cells within 10 min of TBT exposure and the MAP3K, ASK1, after 1 h exposures to TBT. In addition, our results suggest that both TBT and DBT affect the regulation of c-Raf.

  6. [Affective behavioural responses by dogs to tactile human-dog interactions].

    PubMed

    Kuhne, Franziska; Hössler, Johanna C; Struwe, Rainer

    2012-01-01

    The communication of dogs is based on complex, subtle body postures and facial expressions. Some social interaction between dogs includes physical contact. Humans generally use both verbal and tactile signals to communicate with dogs. Hence, interaction between humans and dogs might lead to conflicts because the behavioural responses of dogs to human-dog interaction may be misinterpreted and wrongly assessed. The behavioural responses of dogs to tactile human-dog interactions and human gestures are the focus of this study. The participating dogs (n = 47) were privately owned pets.They were of varying breed and gender.The test consisted of nine randomised test sequences (e. g. petting the dog's head or chest). A test sequence was performed for a period of 30 seconds. The inter-trial interval was set at 60 seconds and the test-retest interval was set at 10 minutes. The frequency and duration of the dogs'behavioural responses were recorded using INTERACT. To examine the behavioural responses of the dogs, a two-way analysis of variance within the linear mixed models procedure of IBM SPSS Statistics 19 was conducted. A significant influence of the test-sequenc order on the dogs' behaviour could be analysed for appeasement gestures (F8,137 = 2.42; p = 0.018), redirected behaviour (F8,161 = 6.31; p = 0.012) and socio-positive behaviour (F8,148 = 6.28; p = 0.012). The behavioural responses of the dogs, which were considered as displacement activities (F8,109 = 2.5; p = 0.014) differed significantly among the test sequences. The response of the dogs, measured as gestures of appeasement, redirected behaviours, and displacement activities, was most obvious during petting around the head and near the paws.The results of this study conspicuously indicate that dogs respond to tactile human-dog interactions with gestures of appeasement and displacement activities. Redirected behaviours, socio-positive behaviours as well displacement activities are behavioural responses which dogs

  7. Depression of cortical activity in humans by mild hypercapnia.

    PubMed

    Thesen, Thomas; Leontiev, Oleg; Song, Tao; Dehghani, Nima; Hagler, Donald J; Huang, Mingxiong; Buxton, Richard; Halgren, Eric

    2012-03-01

    The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2 ) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity.

  8. Depression of Cortical Activity in Humans by Mild Hypercapnia

    PubMed Central

    Thesen, Thomas; Leontiev, Oleg; Song, Tao; Dehghani, Nima; Hagler, Donald J; Huang, Mingxiong; Buxton, Richard; Halgren, Eric

    2013-01-01

    The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity. PMID:21500313

  9. N-Methyl D-Aspartate Receptor Antagonist Kynurenic Acid Affects Human Cortical Development

    PubMed Central

    Bagasrawala, Inseyah; Zecevic, Nada; Radonjić, Nevena V.

    2016-01-01

    Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan degradation, acts as an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist. Elevated levels of KYNA have been observed in pregnant women after viral infections and are considered to play a role in neurodevelopmental disorders. However, the consequences of KYNA-induced NMDAR blockade in human cortical development still remain elusive. To study the potential impact of KYNA on human neurodevelopment, we used an in vitro system of multipotent cortical progenitors, i.e., radial glia cells (RGCs), enriched from human cerebral cortex at mid-gestation (16–19 gestational weeks). KYNA treatment significantly decreased RGCs proliferation and survival by antagonizing NMDAR. This alteration resulted in a reduced number of cortical progenitors and neurons while number and activation of astrocytes increased. KYNA treatment reduced differentiation of RGCs into GABAergic neurons, while differentiation into glutamatergic neurons was relatively spared. Furthermore, in mixed cortical cultures KYNA triggered an inflammatory response as evidenced by increased levels of the pro-inflammatory cytokine IL-6. In conclusion, elevated levels of KYNA play a significant role in human RGC fate determination by antagonizing NMDARs and by activating an inflammatory response. The altered cell composition observed in cell culture following exposure to elevated KYNA levels suggests a mechanism for impairment of cortical circuitry formation in the fetal brain after viral infection, as seen in neurodevelopmental disorders such as schizophrenia. PMID:27746712

  10. Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin.

    PubMed Central

    Stewart, D. J.; Molepo, J. M.; Green, R. M.; Montpetit, V. A.; Hugenholtz, H.; Lamothe, A.; Mikhael, N. Z.; Redmond, M. D.; Gadia, M.; Goel, R.

    1995-01-01

    We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours. PMID:7880744

  11. Resveratrol affects DNA damage induced by ionizing radiation in human lymphocytes in vitro.

    PubMed

    Basso, Emiliano; Regazzo, Giulia; Fiore, Mario; Palma, Valentina; Traversi, Gianandrea; Testa, Antonella; Degrassi, Francesca; Cozzi, Renata

    2016-08-01

    Resveratrol (3,4',5-trihydroxystilbene; RSV) acts on cancer cells in several ways, inducing cell cycle delay and apoptotic death, and enhancing ionizing radiation (IR)-mediated responses. However, fewer studies have examined RSV effects on normal cells. We have treated human lymphocytes in vitro with RSV, either alone or combined with IR, to evaluate its potential use as a radioprotector. We measured the effects of RSV on induction of DNA damage, repair kinetics, and modulation of histone deacetylase activity.

  12. Focus-of-attention for human activity recognition from UAVs

    NASA Astrophysics Data System (ADS)

    Burghouts, G. J.; van Eekeren, A. W. M.; Dijk, J.

    2014-10-01

    This paper presents a system to extract metadata about human activities from full-motion video recorded from a UAV. The pipeline consists of these components: tracking, motion features, representation of the tracks in terms of their motion features, and classification of each track as one of the human activities of interest. We consider these activities: walk, run, throw, dig, wave. Our contribution is that we show how a robust system can be constructed for human activity recognition from UAVs, and that focus-of-attention is needed. We find that tracking and human detection are essential for robust human activity recognition from UAVs. Without tracking, the human activity recognition deteriorates. The combination of tracking and human detection is needed to focus the attention on the relevant tracks. The best performing system includes tracking, human detection and a per-track analysis of the five human activities. This system achieves an average accuracy of 93%. A graphical user interface is proposed to aid the operator or analyst during the task of retrieving the relevant parts of video that contain particular human activities. Our demo is available on YouTube.

  13. Meditation-induced neuroplastic changes in amygdala activity during negative affective processing.

    PubMed

    Leung, Mei-Kei; Lau, Way K W; Chan, Chetwyn C H; Wong, Samuel S Y; Fung, Annis L C; Lee, Tatia M C

    2017-04-10

    Recent evidence suggests that the effects of meditation practice on affective processing and resilience have the potential to induce neuroplastic changes within the amygdala. Notably, literature speculates that meditation training may reduce amygdala activity during negative affective processing. Nonetheless, studies have thus far not verified this speculation. In this longitudinal study, participants (N = 21, 9 men) were trained in awareness-based compassion meditation (ABCM) or matched relaxation training. The effects of meditation training on amygdala activity were examined during passive viewing of affective and neutral stimuli in a non-meditative state. We found that the ABCM group exhibited significantly reduced anxiety and right amygdala activity during negative emotion processing than the relaxation group. Furthermore, ABCM participants who performed more compassion practice had stronger right amygdala activity reduction during negative emotion processing. The lower right amygdala activity after ABCM training may be associated with a general reduction in reactivity and distress. As all participants performed the emotion processing task in a non-meditative state, it appears likely that the changes in right amygdala activity are carried over from the meditation practice into the non-meditative state. These findings suggest that the distress-reducing effects of meditation practice on affective processing may transfer to ordinary states, which have important implications on stress management.

  14. Activation of the human, intermediate-conductance, Ca2+-activated K+ channel by methylxanthines.

    PubMed

    Schrøder, R L; Jensen, B S; Strøbaek, D; Olesen, S P; Christophersen, P

    2000-10-01

    This study demonstrated that the methylxanthines, theophylline, IBMX and caffeine, activate the human, intermediate-conductance, Ca2+-activated K+ channel (hIK) stably expressed in HEK-293 cells. Whole-cell voltage-clamp experiments showed that the hIK current increased reversibly and voltage independently after the addition of methylxanthines. In current-clamp experiments, theophylline dose-dependently hyperpolarised the cell membrane from a resting potential of -18 mV to -56 mV. The methylxanthines did not affect large-conductance (BK) or small-conductance (SK2), Ca2+-activated K+ channels, demonstrating that the effects were not secondary to a rise in intracellular Ca2+. However, the activation of hIK by theophylline required an intracellular [Ca2+] above 30 nM. The hIK current was insensitive to 8-bromoadenosine cyclic 3',5'-monophosphate (8-bromo-cAMP), forskolin, 8-bromoguanosine cyclic 3',5'-monophosphate (8-bromo-cGMP) and sodium nitroprusside. Moreover, in the presence of inhibitors of protein kinase A (PKA) or protein kinase G (PKG) theophylline still activated the current. Finally, mutation of the putative PKA/PKG consensus phosphorylation site (Ser334) had no effect on the theophylline-induced activation of hIK. Since the observed activation is independent of changes in PKA/PKG-phosphorylation and of fluctuations in intracellular Ca2+, we suggest that the methylxanthines interact directly with the hIK protein.

  15. Functional Assessment of Human Coding Mutations Affecting Skin Pigmentation Using Zebrafish

    PubMed Central

    Tsetskhladze, Zurab R.; Canfield, Victor A.; Ang, Khai C.; Wentzel, Steven M.; Reid, Katherine P.; Berg, Arthur S.; Johnson, Stephen L.; Kawakami, Koichi; Cheng, Keith C.

    2012-01-01

    A major challenge in personalized medicine is the lack of a standard way to define the functional significance of the numerous nonsynonymous, single nucleotide coding variants that are present in each human individual. To begin to address this problem, we have used pigmentation as a model polygenic trait, three common human polymorphisms thought to influence pigmentation, and the zebrafish as a model system. The approach is based on the rescue of embryonic zebrafish mutant phenotypes by “humanized” zebrafish orthologous mRNA. Two hypomorphic polymorphisms, L374F in SLC45A2, and A111T in SLC24A5, have been linked to lighter skin color in Europeans. The phenotypic effect of a second coding polymorphism in SLC45A2, E272K, is unclear. None of these polymorphisms had been tested in the context of a model organism. We have confirmed that zebrafish albino fish are mutant in slc45a2; wild-type slc45a2 mRNA rescued the albino mutant phenotype. Introduction of the L374F polymorphism into albino or the A111T polymorphism into slc24a5 (golden) abolished mRNA rescue of the respective mutant phenotypes, consistent with their known contributions to European skin color. In contrast, the E272K polymorphism had no effect on phenotypic rescue. The experimental conclusion that E272K is unlikely to affect pigmentation is consistent with a lack of correlation between this polymorphism and quantitatively measured skin color in 59 East Asian humans. A survey of mutations causing human oculocutaneous albinism yielded 257 missense mutations, 82% of which are theoretically testable in zebrafish. The developed approach may be extended to other model systems and may potentially contribute to our understanding the functional relationships between DNA sequence variation, human biology, and disease. PMID:23071798

  16. Multimodel Estimate of Global Water Resources Affected by Human Interventions and Climate Change

    NASA Astrophysics Data System (ADS)

    Haddeland, I.; Biemans, H.; Flörke, M.; Hanasaki, N.; Stacke, T.; Tessler, Z. D.; Wada, Y.

    2013-12-01

    Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural or domestic purposes. Climate change is expected to additionally affect water supply and demand. Several global hydrologic models have recently implemented reservoir operations and water withdrawals in their modeling schemes. Seven of these models (H08, LPJmL, PCR-GLOBWB, MPI-HM, VIC, WaterGAP and WBM) have been run within the framework of two model inter-comparison projects - the currently running Inter-sectoral Impact Model Intercomparison Project (ISI-MIP) and its predecessor on the water sector the Water Model Intercomparison Project (WaterMIP). In both projects hydrological models were forced with multiple climate projections from different Atmosphere-Ocean General Circulation Models (AOGCMs) taking into account present day human interventions on the hydrological cycle such as dams and water withdrawals. By integrating results from the two projects we benefit form a large ensemble size that allows for assessments of uncertainties from climate projections from different AOGCMs. Here, multimodel analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared. The results indicate that direct human impacts on the annual water cycle in some regions are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2K). In many river basins the relative effects of human interventions are much larger at the seasonal level than at the annual level. There is, however, a considerable spread in the model estimates of these impacts. Possible reasons for this spread, e.g. differences in the reservoir operation schemes, are discussed.

  17. Use of genotoxicity tests in a TIE to identify chemicals potentially affecting human health

    SciTech Connect

    Goudey, J.S.; Shaw, R.D.; Swanson, S.M.; Nadeau, S.

    1995-12-31

    Imperial Oil operates a sour gas processing plant in southern Alberta that has, for the past several years, been the focus of considerable public and regulatory concern over perceived contamination of soils and groundwater on a nearby ranch. Elevated concentrations of DOC ({approximately}140 mg/L) have been received in groundwater underlying the plant site. Two process-related chemicals, sulfolane and diisopropanolamine (DIPA), had been previously identified as the primary components of the DOC plume, although the chemicals associated with 30% of the DOC could not be identified. A risk assessment was initiated in 1994 to determine whether off-site migration of sulfolane and DIPA or of other unidentified contaminants poses a risks to human health and/or ecological receptors. One component of the risk assessment included conducting a TIE to help identify the chemical(s) in contaminated groundwater underlying the gas plant that might adversely affect human health. Three endpoints were utilized in the TIE: MicroTox, SOS-Chromotest and the Ames test. MicroTox was used since it exhibited a response to whole groundwater from the site, while the genotoxicity tests were used because DIPA reportedly causes a response in the Ames test and because of the concern over potential human health affects arising from other unidentified contaminants. Results of the TIE indicated that the chemicals causing the toxicity in the groundwater sample were water soluble compounds, with similar characteristics to the process chemicals used at the gas plant and detected at high concentrations in groundwater from the plant site. These results provided additional evidence to help focus the risk assessment on the chemicals sulfolane and diisopropanolamine.

  18. Reshaping Human Antibodies: Grafting an Antilysozyme Activity

    NASA Astrophysics Data System (ADS)

    Verhoeyen, Martine; Milstein, Cesar; Winter, Greg

    1988-03-01

    The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the ``humanizing'' of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.

  19. Saturation deficit and deer density affect questing activity and local abundance of Ixodes ricinus (Acari, Ixodidae) in Italy.

    PubMed

    Tagliapietra, V; Rosà, R; Arnoldi, D; Cagnacci, F; Capelli, G; Montarsi, F; Hauffe, H C; Rizzoli, A

    2011-12-29

    The wood tick Ixodes ricinus, one of the most common arthropod-borne disease vectors, is of increasing relevance for human and animal health in Europe. The aim of this study was to determine the relative contribution of several abiotic and biotic factors potentially affecting questing activity and local abundance of I. ricinus in Italy, considering the scale at which these factors interact with the host-seeking ticks. Within EDEN, a large-scale EU collaborative project on eco-epidemiology of vector-borne diseases, we collected questing ticks for three consecutive years using a standard protocol at eleven sites in the Italian Alps and Apennines. A total of 25 447 I. ricinus were collected. All sites showed the same annual pattern of tick activity (bimodal for nymphs and unimodal for larvae and adults), although the abundance of nymphs was statistically different between sites and years. A Generalized Linear Mixed Model and a Linear Mixed Model fitted to data for nymphs, showed that while the principal variables affecting the local abundance of questing ticks were saturation deficit (an index combining temperature and relative humidity) and red deer density, the most important variable affecting questing nymph activity was saturation deficit. As for the timing of seasonal emergence, we confirmed that the threshold temperature at this latitude for larvae is 10°C (mean maximum) while that for nymphs is 8°C.

  20. Tumoricidal activity of human monocytes activated in vitro by free and liposome-encapsulated human lymphokines.

    PubMed Central

    Kleinerman, E S; Schroit, A J; Fogler, W E; Fidler, I J

    1983-01-01

    Human peripheral blood mononuclear cells from normal donors obtained by separation on a Percoll gradient were incubated with free or liposome-entrapped lymphokines produced from concanavalin A-stimulated lymphocytes and then were tested for cytotoxic activity against tumor cells. The treated monocytes lysed tumorigenic melanoma and glioblastoma target cells, but had no effect on three types of nontumorigenic target cells. The activation of monocytes to become tumoricidal was caused by macrophage-activating factor (MAF) and not by contamination with endotoxins, concanavalin A, or interferon. The endocytosis of liposomes containing MAF, but not of those containing control supernatants, led to the activation of cytotoxic properties in the monocytes. Activation by liposome-encapsulated MAF was very efficient and required less than 1/800th of the amount of free MAF necessary to achieve the same levels of cytotoxicity. Thus, the encapsulation of mitogen-induced MAF in liposomes could provide an effective approach for the activation of blood monocytes in situ. Images FIGURE 2 PMID:6348087

  1. Identification of Climatic Factors Affecting the Epidemiology of Human West Nile Virus Infections in Northern Greece.

    PubMed

    Stilianakis, Nikolaos I; Syrris, Vasileios; Petroliagkis, Thomas; Pärt, Peeter; Gewehr, Sandra; Kalaitzopoulou, Stella; Mourelatos, Spiros; Baka, Agoritsa; Pervanidou, Danai; Vontas, John; Hadjichristodoulou, Christos

    2016-01-01

    Climate can affect the geographic and seasonal patterns of vector-borne disease incidence such as West Nile Virus (WNV) infections. We explore the association between climatic factors and the occurrence of West Nile fever (WNF) or West Nile neuro-invasive disease (WNND) in humans in Northern Greece over the years 2010-2014. Time series over a period of 30 years (1979-2008) of climatic data of air temperature, relative humidity, soil temperature, volumetric soil water content, wind speed, and precipitation representing average climate were obtained utilising the ECMWF's (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-Interim) system allowing for a homogeneous set of data in time and space. We analysed data of reported human cases of WNF/WNND and Culex mosquitoes in Northern Greece. Quantitative assessment resulted in identifying associations between the above climatic variables and reported human cases of WNF/WNND. A substantial fraction of the cases was linked to the upper percentiles of the distribution of air and soil temperature for the period 1979-2008 and the lower percentiles of relative humidity and soil water content. A statistically relevant relationship between the mean weekly value climatic anomalies of wind speed (negative association), relative humidity (negative association) and air temperature (positive association) over 30 years, and reported human cases of WNF/WNND during the period 2010-2014 could be shown. A negative association between the presence of WNV infected Culex mosquitoes and wind speed could be identified. The statistically significant associations could also be confirmed for the week the WNF/WNND human cases appear and when a time lag of up to three weeks was considered. Similar statistically significant associations were identified with the weekly anomalies of the maximum and minimum values of the above climatic factors. Utilising the ERA-Interim re-analysis methodology it could be shown that besides air

  2. Identification of Climatic Factors Affecting the Epidemiology of Human West Nile Virus Infections in Northern Greece

    PubMed Central

    Stilianakis, Nikolaos I.; Syrris, Vasileios; Petroliagkis, Thomas; Pärt, Peeter; Gewehr, Sandra; Kalaitzopoulou, Stella; Mourelatos, Spiros; Baka, Agoritsa; Pervanidou, Danai; Vontas, John; Hadjichristodoulou, Christos

    2016-01-01

    Climate can affect the geographic and seasonal patterns of vector-borne disease incidence such as West Nile Virus (WNV) infections. We explore the association between climatic factors and the occurrence of West Nile fever (WNF) or West Nile neuro-invasive disease (WNND) in humans in Northern Greece over the years 2010–2014. Time series over a period of 30 years (1979–2008) of climatic data of air temperature, relative humidity, soil temperature, volumetric soil water content, wind speed, and precipitation representing average climate were obtained utilising the ECMWF’s (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-Interim) system allowing for a homogeneous set of data in time and space. We analysed data of reported human cases of WNF/WNND and Culex mosquitoes in Northern Greece. Quantitative assessment resulted in identifying associations between the above climatic variables and reported human cases of WNF/WNND. A substantial fraction of the cases was linked to the upper percentiles of the distribution of air and soil temperature for the period 1979–2008 and the lower percentiles of relative humidity and soil water content. A statistically relevant relationship between the mean weekly value climatic anomalies of wind speed (negative association), relative humidity (negative association) and air temperature (positive association) over 30 years, and reported human cases of WNF/WNND during the period 2010–2014 could be shown. A negative association between the presence of WNV infected Culex mosquitoes and wind speed could be identified. The statistically significant associations could also be confirmed for the week the WNF/WNND human cases appear and when a time lag of up to three weeks was considered. Similar statistically significant associations were identified with the weekly anomalies of the maximum and minimum values of the above climatic factors. Utilising the ERA-Interim re-analysis methodology it could be shown that besides

  3. The cross-mammalian neurophenomenology of primal emotional affects: From animal feelings to human therapeutics.

    PubMed

    Panksepp, Jaak

    2016-06-01

    The neural correlates of human emotions are easy to harvest. In contrast, the neural constitution of emotional feelings in humans has resisted systematic scientific analysis. This review summarizes how preclinical affective neuroscience initiatives are making progress in decoding the neural nature of such feelings in animal brains. This has been achieved by studying the rewarding and punishing effects of deep brain stimulation (DBS) of subcortical emotional networks (labeled SEEING, RAGE, FEAR, LUST, CARE, PANIC, and PLAY systems) that evoke distinct emotion action patterns, as well as rewarding and punishing effects in animals. The implications of this knowledge for development of new psychiatric interventions, especially depression, are discussed. Three new antidepressive therapeutics arising from this work are briefly noted: 1) DBS of the medial forebrain bundle (MFB) in humans, 2) reduction of psychological pain that may arise from excessive PANIC arousal, and 3) facilitation of social joy through the study of social play in rats The overall argument is that we may more readily develop new psychiatric interventions through preclinical models if we take animal emotional feelings seriously, as opposed to just behavioral changes, as targets for development of new treatments.

  4. Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells

    PubMed Central

    Trevisan, Marta; Desole, Giovanna; Costanzi, Giulia; Lavezzo, Enrico; Palù, Giorgio; Barzon, Luisa

    2017-01-01

    Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts. The reprogramming efficiency of the methods based on episomal and Sendai virus vectors was higher than that of the retroviral vector-based approach. All human iPSC clones derived with the different methods showed the typical features of pluripotent stem cells, including the expression of alkaline phosphatase and stemness maker genes, and could give rise to the three germ layer derivatives upon embryoid bodies assay. Microarray analysis confirmed the presence of typical stem cell gene expression profiles in all iPSC clones and did not identify any significant difference among reprogramming methods. In conclusion, the use of different reprogramming methods is equivalent and does not affect gene expression profile of the derived human iPSCs. PMID:28117672

  5. Recombination affects accumulation of damaging and disease-associated mutations in human populations.

    PubMed

    Hussin, Julie G; Hodgkinson, Alan; Idaghdour, Youssef; Grenier, Jean-Christophe; Goulet, Jean-Philippe; Gbeha, Elias; Hip-Ki, Elodie; Awadalla, Philip

    2015-04-01

    Many decades of theory have demonstrated that, in non-recombining systems, slightly deleterious mutations accumulate non-reversibly, potentially driving the extinction of many asexual species. Non-recombining chromosomes in sexual organisms are thought to have degenerated in a similar fashion; however, it is not clear the extent to which damaging mutations accumulate along chromosomes with highly variable rates of crossing over. Using high-coverage sequencing data from over 1,400 individuals in the 1000 Genomes and CARTaGENE projects, we show that recombination rate modulates the distribution of putatively deleterious variants across the entire human genome. Exons in regions of low recombination are significantly enriched for deleterious and disease-associated variants, a signature varying in strength across worldwide human populations with different demographic histories. Regions with low recombination rates are enriched for highly conserved genes with essential cellular functions and show an excess of mutations with demonstrated effects on health, a phenomenon likely affecting disease susceptibility in humans.

  6. Thrombopoietin potentiates agonist-stimulated activation of p38 mitogen-activated protein kinase in human platelets.

    PubMed

    Ezumi, Y; Nishida, E; Uchiyama, T; Takayama, H

    1999-07-22

    Thrombopoietin (TPO) plays a crucial role in megakaryocyte differentiation and platelet production. c-Mpl, a receptor for TPO, is also expressed in terminally differentiated platelets. We investigated the effects of TPO on activation of p38 mitogen-activated protein kinase in human platelets. Thrombin, a thrombin receptor agonist peptide, a thromboxane A(2) analogue, collagen, crosslinking the glycoprotein VI, ADP, and epinephrine, but not phorbol 12, 13-dibutyrate activated p38. TPO did not activate p38 by itself, whereas TPO pretreatment potentiated the agonist-induced activation of p38. TPO did not promote phosphorylation of Hsp27 and cytosolic phospholipase A(2) by itself, but enhanced thrombin-induced phosphorylation of them. The specific p38 inhibitor SB203580 strongly inhibited such phosphorylation. Thus, TPO possesses the priming effect on p38 activation in human platelets and could affect platelet functions through the p38 pathway.

  7. Growth status significantly affects the response of human lung cancer cells to antitumor polyamine-analogue exposure.

    PubMed

    Carlisle, Diane L; Devereux, Wendy L; Hacker, Amy; Woster, Patrick M; Casero, Robert A

    2002-08-01

    Human solid tumors frequently have a relatively small growth fraction,which interferes with the action of many chemotherapeutic agents that target actively cycling cells. Several polyamine analogues are currently being developed for clinical application against human solid tumors including N1,N11-bis(ethyl)norspermine. Therefore, an effort was made to examine the effects of growth rate on polyamine-analogue efficacy. Low growth fraction (LGF) cell cultures of the human non-small cell lung cancer cell line NCI-H157 were generated to partially mimic solid tumors with low mitotic indices. Log-phase cells were compared with LGF cells with respect to cell survival and biochemical effects after exposure to polyamine analogues. The results demonstrate generally that LGF NCI-H157 cells were sensitive to analogue treatment. However, the dose necessary to elicit a response in LGF cells was an order of magnitude higher than the dose needed in log-phase cells. Additionally, the biochemical effects of analogues were similar between log phase and LGF cells with regard to a down-regulation of polyamine biosynthesis as measured by ornithine decarboxylase activity and an increase in polyamine catabolism as indicated by an increase in spermidine/spermine N1-acetyltransferase activity. However, biochemical effects were less dramatic in the LGF cells than those observed in the log-phase cells. The overall results of these studies suggest that the growth status of solid tumors can significantly affect the response to antitumor polyamine analogues, and growth fraction must be considered in the continued development and use of the polyamine analogues.

  8. Drive for thinness, affect regulation and physical activity in eating disorders: a daily life study.

    PubMed

    Vansteelandt, Kristof; Rijmen, Frank; Pieters, Guido; Probst, Michel; Vanderlinden, Johan

    2007-08-01

    Using Ecological Momentary Assessment, the within patient associations between drive for thinness, emotional states, momentary urge to be physically active and physical activity were studied in 32 inpatients with an eating disorder. Participants received an electronic device and had to indicate at nine random times a day during 1 week their momentary drive for thinness, positive and negative emotional states and their urge to be physically active and physical activity. Multilevel analyses indicated that patients with higher mean levels for urge to be physically active were characterized by lower body mass index (BMI) and chronically negative affect whereas patients with higher mean levels for physical activity were characterized by lower BMI and higher dispositions for drive for thinness. In addition, within patient relations between drive for thinness and urge to be physically active were moderated by BMI and chronically negative affect whereas within patient relations between drive for thinness and physical activity were moderated by BMI. Finally, also positive emotional states were significantly associated with physical activity within patients. By using a daily process design, characteristics of physical activity were revealed that have not been identified with assessment methods that have a lower time resolution.

  9. The Affective Slider: A Digital Self-Assessment Scale for the Measurement of Human Emotions

    PubMed Central

    Betella, Alberto; Verschure, Paul F. M. J.

    2016-01-01

    Self-assessment methods are broadly employed in emotion research for the collection of subjective affective ratings. The Self-Assessment Manikin (SAM), a pictorial scale developed in the eighties for the measurement of pleasure, arousal, and dominance, is still among the most popular self-reporting tools, despite having been conceived upon design principles which are today obsolete. By leveraging on state-of-the-art user interfaces and metacommunicative pictorial representations, we developed the Affective Slider (AS), a digital self-reporting tool composed of two slider controls for the quick assessment of pleasure and arousal. To empirically validate the AS, we conducted a systematic comparison between AS and SAM in a task involving the emotional assessment of a series of images taken from the International Affective Picture System (IAPS), a database composed of pictures representing a wide range of semantic categories often used as a benchmark in psychological studies. Our results show that the AS is equivalent to SAM in the self-assessment of pleasure and arousal, with two added advantages: the AS does not require written instructions and it can be easily reproduced in latest-generation digital devices, including smartphones and tablets. Moreover, we compared new and normative IAPS ratings and found a general drop in reported arousal of pictorial stimuli. Not only do our results demonstrate that legacy scales for the self-report of affect can be replaced with new measurement tools developed in accordance to modern design principles, but also that standardized sets of stimuli which are widely adopted in research on human emotion are not as effective as they were in the past due to a general desensitization towards highly arousing content. PMID:26849361

  10. Cold stress affects H(+)-ATPase and phospholipase D activity in Arabidopsis.

    PubMed

    Muzi, Carlo; Camoni, Lorenzo; Visconti, Sabina; Aducci, Patrizia

    2016-11-01

    Low temperature is an environmental stress that greatly influences plant performance and distribution. Plants exposed to cold stress exhibit modifications of plasma membrane physical properties that can affect their functionality. Here it is reported the effect of low temperature exposure of Arabidopsis plants on the activity of phospholipase D and H(+)-ATPase, the master enzyme located at the plasma membrane. The H(+)-ATPase activity was differently affected, depending on the length of cold stress imposed. In particular, an exposure to 4 °C for 6 h determined the strong inhibition of the H(+)-ATPase activity, that correlates with a reduced association with the regulatory 14-3-3 proteins. A longer exposure first caused the full recovery of the enzymatic activity followed by a significant activation, in accordance with both the increased association with 14-3-3 proteins and induction of H(+)-ATPase gene transcription. Different time lengths of cold stress treatment were also shown to strongly stimulate the phospholipase D activity and affect the phosphatidic acid levels of the plasma membranes. Our results suggest a functional correlation between the activity of phospholipase D and H(+)-ATPase mediated by phosphatidic acid release during the cold stress response.

  11. Interactions between occlusion and human brain function activities.

    PubMed

    Ohkubo, C; Morokuma, M; Yoneyama, Y; Matsuda, R; Lee, J S

    2013-02-01

    There are few review articles in the area of human research that focus on the interactions between occlusion and brain function. This systematic review discusses the effect of occlusion on the health of the entire body with a focus on brain function. Available relevant articles in English from 1999 to 2011 were assessed in an online database and as hard copies in libraries. The selected 19 articles were classified into the following five categories: chewing and tongue movements, clenching and grinding, occlusal splints and occlusal interference, prosthetic rehabilitation, and pain and stimulation. The relationships between the brain activity observed in the motor and sensory cortices and movements of the oral and maxillofacial area, such as those produced by gum chewing, tapping and clenching, were investigated. It was found that the sensorimotor cortex was also affected by the placement of the occlusal interference devices, splints and implant prostheses. Brain activity may change depending on the strength of the movements in the oral and maxillofacial area. Therefore, mastication and other movements stimulate the activity in the cerebral cortex and may be helpful in preventing degradation of a brain function. However, these findings must be verified by evidence gathered from more subjects.

  12. Allergen extracts directly mobilize and activate human eosinophils.

    PubMed

    Svensson, Lena; Rudin, Anna; Wennerås, Christine

    2004-06-01

    Allergic diseases are characterized by the presence of eosinophils, which are recruited to the affected tissues by chemoattractants produced by T cells, mast cells and epithelium. Our objective was to evaluate if allergens can directly activate human eosinophils. The capacity of purified allergen extracts to elicit eosinophil chemotaxis, respiratory burst, degranulation and up-regulation of the adhesion molecule complement receptor 3 (CR3) was determined in eosinophils isolated from healthy blood donors. Eosinophils stimulated with an extract from house dust mite (HDM) released the granule protein major basic protein (MBP) and up-regulated the surface expression of CR3. Cat allergen extracts also induced the up-regulation of CR3, but not the release of MBP; instead cat, as well as birch and grass allergens, elicited the release of eosinophil peroxidase (EPO). In addition, grass pollen extract caused the secretion of MBP. None of the allergens stimulated eosinophilic cationic protein release, nor production of free oxygen radicals. Both HDM and birch extracts were chemotactic for eosinophils. These findings establish that common aeroallergens can directly activate eosinophils in vitro. We propose that eosinophil activation in vivo is not exclusively mediated by cytokines and chemokines of the allergic inflammatory reaction, but could partly be the result of direct interaction between allergens and eosinophils.

  13. Exosomes: novel effectors of human platelet lysate activity.

    PubMed

    Torreggiani, E; Perut, F; Roncuzzi, L; Zini, N; Baglìo, S R; Baldini, N

    2014-09-22

    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

  14. Enhancing human spermine synthase activity by engineered mutations.

    PubMed

    Zhang, Zhe; Zheng, Yueli; Petukh, Margo; Pegg, Anthony; Ikeguchi, Yoshihiko; Alexov, Emil

    2013-01-01

    Spermine synthase (SMS) is an enzyme which function is to convert spermidine into spermine. It was shown that gene defects resulting in amino acid changes of the wild type SMS cause Snyder-Robinson syndrome, which is a mild-to-moderate mental disability associated with osteoporosis, facial asymmetry, thin habitus, hypotonia, and a nonspecific movement disorder. These disease-causing missense mutations were demonstrated, both in silico and in vitro, to affect the wild type function of SMS by either destabilizing the SMS dimer/monomer or directly affecting the hydrogen bond network of the active site of SMS. In contrast to these studies, here we report an artificial engineering of a more efficient SMS variant by transferring sequence information from another organism. It is confirmed experimentally that the variant, bearing four amino acid substitutions, is catalytically more active than the wild type. The increased functionality is attributed to enhanced monomer stability, lowering the pKa of proton donor catalytic residue, optimized spatial distribution of the electrostatic potential around the SMS with respect to substrates, and increase of the frequency of mechanical vibration of the clefts presumed to be the gates toward the active sites. The study demonstrates that wild type SMS is not particularly evolutionarily optimized with respect to the reaction spermidine → spermine. Having in mind that currently there are no variations (non-synonymous single nucleotide polymorphism, nsSNP) detected in healthy individuals, it can be speculated that the human SMS function is precisely tuned toward its wild type and any deviation is unwanted and disease-causing.

  15. TGF-β stimulation in human and murine cells reveals commonly affected biological processes and pathways at transcription level

    PubMed Central

    2014-01-01

    Background The TGF-β signaling pathway is a fundamental pathway in the living cell, which plays a key role in many central cellular processes. The complex and sometimes contradicting mechanisms by which TGF-β yields phenotypic effects are not yet completely understood. In this study we investigated and compared the transcriptional response profile of TGF-β1 stimulation in different cell types. For this purpose, extensive experiments are performed and time-course microarray data are generated in human and mouse parenchymal liver cells, human mesenchymal stromal cells and mouse hematopoietic progenitor cells at different time points. We applied a panel of bioinformatics methods on our data to uncover common patterns in the dynamic gene expression response in respective cells. Results Our analysis revealed a quite variable and multifaceted transcriptional response profile of TGF-β1 stimulation, which goes far beyond the well-characterized classical TGF-β1 signaling pathway. Nonetheless, we could identify several commonly affected processes and signaling pathways across cell types and species. In addition our analysis suggested an important role of the transcription factor EGR1, which appeared to have a conserved influence across cell-types and species. Validation via an independent dataset on A549 lung adenocarcinoma cells largely confirmed our findings. Network analysis suggested explanations, how TGF-β1 stimulation could lead to the observed effects. Conclusions The analysis of dynamical transcriptional response to TGF-β treatment experiments in different human and murine cell systems revealed commonly affected biological processes and pathways, which could be linked to TGF-β1 via network analysis. This helps to gain insights about TGF-β pathway activities in these cell systems and its conserved interactions between the species and tissue types. PMID:24886091

  16. Human factors activities in teleoperator development at the Oak Ridge National Laboratory

    SciTech Connect

    Draper, J.V.; Herndon, J.N.

    1986-01-01

    The Consolidated Fuel Reprocessing Program (CFRP) at the Oak Ridge National Laboratory is developing advanced teleoperator systems for maintenance of future nuclear reprocessing facilities. Remote maintenance systems developed by the CFRP emphasize man-in-the-loop teleoperation. Consequently, human factors issues which affect teleoperator performance must be addressed. This papers surveys research and development activities carried out by the human factors group within the Remote Control Engineering Task of the CFRP.

  17. Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models.

    PubMed

    Magri, Laura; Cominelli, Manuela; Cambiaghi, Marco; Cursi, Marco; Leocani, Letizia; Minicucci, Fabio; Poliani, Pietro Luigi; Galli, Rossella

    2013-09-01

    Tuberous sclerosis complex (TSC) is a dominantly inherited disease with high penetrance and morbidity, and is caused by mutations in either of two genes, TSC1 or TSC2. Most affected individuals display severe neurological manifestations - such as intractable epilepsy, mental retardation and autism - that are intimately associated with peculiar CNS lesions known as cortical tubers (CTs). The existence of a significant genotype-phenotype correlation in individuals bearing mutations in either TSC1 or TSC2 is highly controversial. Similar to observations in humans, mouse modeling has suggested that a more severe phenotype is associated with mutation in Tsc2 rather than in Tsc1. However, in these mutant mice, deletion of either gene was achieved in differentiated astrocytes. Here, we report that loss of Tsc1 expression in undifferentiated radial glia cells (RGCs) early during development yields the same phenotype detected upon deletion of Tsc2 in the same cells. Indeed, the same aberrations in cortical cytoarchitecture, hippocampal disturbances and spontaneous epilepsy that have been detected in RGC-targeted Tsc2 mutants were observed in RGC-targeted Tsc1 mutant mice. Remarkably, thorough characterization of RGC-targeted Tsc1 mutants also highlighted subventricular zone (SVZ) disturbances as well as STAT3-dependent and -independent developmental-stage-specific defects in the differentiation potential of ex-vivo-derived embryonic and postnatal neural stem cells (NSCs). As such, deletion of either Tsc1 or Tsc2 induces mostly overlapping phenotypic neuropathological features when performed early during neurogenesis, thus suggesting that the timing of mTOR activation is a key event in proper neural development.

  18. Training experience in gestures affects the display of social gaze in baboons' communication with a human.

    PubMed

    Bourjade, Marie; Canteloup, Charlotte; Meguerditchian, Adrien; Vauclair, Jacques; Gaunet, Florence

    2015-01-01

    Gaze behaviour, notably the alternation of gaze between distal objects and social partners that accompanies primates' gestural communication is considered a standard indicator of intentionality. However, the developmental precursors of gaze behaviour in primates' communication are not well understood. Here, we capitalized on the training in gestures dispensed to olive baboons (Papio anubis) as a way of manipulating individual communicative experience with humans. We aimed to delineate the effects of such a training experience on gaze behaviour displayed by the monkeys in relation with gestural requests. Using a food-requesting paradigm, we compared subjects trained in requesting gestures (i.e. trained subjects) to naïve subjects (i.e. control subjects) for their occurrences of (1) gaze behaviour, (2) requesting gestures and (3) temporal combination of gaze alternation with gestures. We found that training did not affect the frequencies of looking at the human's face, looking at food or alternating gaze. Hence, social gaze behaviour occurs independently from the amount of communicative experience with humans. However, trained baboons-gesturing more than control subjects-exhibited most gaze alternation combined with gestures, whereas control baboons did not. By reinforcing the display of gaze alternation along with gestures, we suggest that training may have served to enhance the communicative function of hand gestures. Finally, this study brings the first quantitative report of monkeys producing requesting gestures without explicit training by humans (controls). These results may open a window on the developmental mechanisms (i.e. incidental learning vs. training) underpinning gestural intentional communication in primates.

  19. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    PubMed

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  20. Effects of human subsistence activities on forest birds in northern Kenya.

    PubMed

    Borghesio, Luca

    2008-04-01

    Indigenous tribes and conservation biologists may have common goals and may be able to collaborate on the maintenance of biodiversity, but few researchers have evaluated the impacts and potential benefits of human subsistence activities. I studied the effects of subsistence activities (primarily wood collection) of nomadic pastoralists in 3 Afromontane forests of northern Kenya. In surveys of 404, 25-m-radius plots, I recorded vegetation structure and composition of the forest bird community. Plots with higher levels of human activity had significantly different vegetation structure, with more-open canopies, more grass, and fewer tree stems. Nectarivores (abundance +231%) and aerial insectivores (+66%) were more abundant in plots with more-intense wood collecting than in plots with less human activity, whereas abundance of forest specialists (-28%) decreased in plots with more-intense human activity. Abundance of 58% of the bird species either increased or decreased significantly in plots with more-intense human activity. Generally, the number of individuals of forest specialists decreased (6 of 7 species showed significant responses) and the number of individuals of edge and nonforest species increased with increasing human activity. Canonical correspondence analysis showed that an intensification of human activities would favor nectarivores, aerial insectivores, granivores, and omnivores and would negatively affect large-sized, ground-foraging species and arboreal frugivores. Subsistence human activities favored the invasion of forest by edge species at the expense of forest specialists; thus, further intensification of forest exploitation by local peoples is not recommended. At the same time, however, subsistence activities in northern Kenya forests appeared to increase the structural diversity of the vegetation and provided suitable habitat for part (but not all) of the forest avifauna, which suggests that subsistence human activities may have a role in the

  1. The level of physical activity affects the health of older adults despite being active

    PubMed Central

    Fernandez-Alonso, Lorena; Muñoz-García, Daniel; La Touche, Roy

    2016-01-01

    Health care in the ageing population is becoming a crucial issue, due to the quality of life. Physical activity, is of primary importance for older adults. This report compared the physical activity in two active older adults population with functionality, quality of life, and depression symptoms. A cross-sectional study was developed with 64 older adults. Physical activity was assessed through the Yale Physical Activity Survey for classification into a less activity (LA) group and a more activity (MA) group. Afterwards, the other health variables were measured through specific questionnaires: the quality of life with the EuroQol (EuroQol five dimensions questionnaire, EQ-5D), functionality with the Berg balance scale (BBS) and depression symptoms with the geriatric depression scale (GDS). There is a statistical significant difference between groups for the BBS (t=2.21; P=0.03, d=0.27). The Pearson correlation analysis shows in LA group a moderate correlation between the BBS and age (r=−0.539; P<0.01) and EQ-5D (r=0.480; P<0.01). Moreover, both groups had a moderate negative correlation between GDS and the the EQ-5D time trade-off (r=−0.543; P=0.02). Active older adults with different amounts of physical activity differ in the BBS. This functional score was higher in the MA group. When observing to quality of life, only the LA group was negatively associated with age while in both groups were associated with depression index. PMID:27419115

  2. Entrapped elemental selenium nanoparticles affect physicochemical properties of selenium fed activated sludge.

    PubMed

    Jain, Rohan; Seder-Colomina, Marina; Jordan, Norbert; Dessi, Paolo; Cosmidis, Julie; van Hullebusch, Eric D; Weiss, Stephan; Farges, François; Lens, Piet N L

    2015-09-15

    Selenite containing wastewaters can be treated in activated sludge systems, where the total selenium is removed from the wastewater by the formation of elemental selenium nanoparticles, which are trapped in the biomass. No studies have been carried out so far on the characterization of selenium fed activated sludge flocs, which is important for the development of this novel selenium removal process. This study showed that more than 94% of the trapped selenium in activated sludge flocs is in the form of elemental selenium, both as amorphous/monoclinic selenium nanospheres and trigonal selenium nanorods. The entrapment of the elemental selenium nanoparticles in the selenium fed activated sludge flocs leads to faster settling rates, higher hydrophilicity and poorer dewaterability compared to the control activated sludge (i.e., not fed with selenite). The selenium fed activated sludge showed a less negative surface charge density as compared to the control activated sludge. The presence of trapped elemental selenium nanoparticles further affected the spatial distribution of Al and Mg in the activated sludge flocs. This study demonstrated that the formation and subsequent trapping of elemental selenium nanoparticles in the activated sludge flocs affects their physicochemical properties.

  3. Activation of ERK mitogen-activated protein kinase in human cells by the mycotoxin patulin

    SciTech Connect

    Wu, T.-S.; Yu, F.-Y.; Su, C.-C.; Kan, J.-C.; Chung, C.-P.; Liu, B.-H. . E-mail: bingliu@csmu.edu.tw

    2005-09-01

    Patulin (PAT), a mycotoxin produced by certain species of Penicillium and Aspergillus, is often detectable in moldy fruits and their derivative products. PAT led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 {mu}M PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 h incubation with 0.05 {mu}M of PAT. Treatment of human PBMCs for 30 min with 30 {mu}M PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 {mu}M PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression.

  4. Reaction conditions affecting the relationship between thiobarbituric acid reactivity and lipid peroxides in human plasma.

    PubMed

    Lapenna, D; Ciofani, G; Pierdomenico, S D; Giamberardino, M A; Cuccurullo, F

    2001-08-01

    The thiobarbituric acid (TBA) reactivity of human plasma was studied to evaluate its adequacy in quantifying lipid peroxidation as an index of systemic oxidative stress. Two spectrophotometric TBA tests based on the use of either phosphoric acid (pH 2.0, method A) or trichloroacetic plus hydrochloric acid (pH 0.9, method B) were employed with and without sodium sulfate (SS) to inhibit sialic acid (SA) reactivity with TBA. To correct for background absorption, the absorbance values at 572 nm were subtracted from those at 532 nm, which represent the absorption maximum of the TBA:MDA adduct. Method B gave values of TBA-reactive substances (TBARS) 2-fold higher than those detected with method A. SS lowered TBARS by about 50% with both methods, indicating a significant involvement of SA in plasma TBA reactivity. Standard SA, at a physiologically relevant concentration of 1.5 mM, reacted with TBA, creating interference problems, which were substantially eliminated by SS plus correction for background absorbance. When method B was carried out in the lipid and protein fraction of plasma, SS inhibited by 65% TBARS formation only in the latter. Protein TBARS may be largely ascribed to SA-containing glycoproteins and, to a minor extent, protein-bound MDA. Indeed, EDTA did not affect protein TBARS assessed in the presence of SS. TBA reactivity of whole plasma and of its lipid fraction was instead inhibited by EDTA, suggesting that lipoperoxides (and possibly monofunctional lipoperoxidation aldehydes) are involved as MDA precursors in the TBA test. Pretreatment of plasma with KI, a specific reductant of hydroperoxides, decreased TBARS by about 27%. Moreover, aspirin administration to humans to inhibit prostaglandin endoperoxide generation reduced plasma TBARS by 40%. In conclusion, reaction conditions affect the relationship between TBA reactivity and lipid peroxidation in human plasma. After correction for the interfering effects of SA in the TBA test, 40% of plasma TBARS

  5. Affective regulation of stereotype activation: It’s the (accessible) thought that counts

    PubMed Central

    Huntsinger, Jeffrey R.; Sinclair, Stacey; Dunn, Elizabeth; Clore, Gerald L.

    2010-01-01

    Extant research demonstrates that positive affect, compared to negative affect, increases stereotyping. In four experiments we explore whether the link between affect and stereotyping depends, critically, on the relative accessibility of stereotype-relevant thoughts and response tendencies. As well as manipulating mood, we measured or manipulated the accessibility of egalitarian response tendencies (Experiments 1-2) and counter-stereotypic thoughts (Experiments 3-4). In the absence of such response tendencies and thoughts, people in positive moods displayed greater stereotype activation —consistent with past research. By contrast, in the presence of accessible egalitarian response tendencies or counter-stereotypic thoughts, people in positive moods exhibited less stereotype activation than those in negative moods. PMID:20363909

  6. Unraveling dynamics of human physical activity patterns in chronic pain conditions

    NASA Astrophysics Data System (ADS)

    Paraschiv-Ionescu, Anisoara; Buchser, Eric; Aminian, Kamiar

    2013-06-01

    Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a `signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.

  7. Can Mood-Inducing Videos Affect Problem-Solving Activities in a Web-Based Environment?

    ERIC Educational Resources Information Center

    Verleur, Ria; Verhagen, Plon W.; Heuvelman, Ard

    2007-01-01

    The purpose of this study was to examine whether a video-induced positive and negative mood has a differential effect on subsequent problem-solving activities in a web-based environment. The study also examined whether task conditions (task demands) moderated the mood effect. As in traditional experimental mood-effect studies, the affective video…

  8. Elements of Design-Based Science Activities That Affect Students' Motivation

    ERIC Educational Resources Information Center

    Jones, Brett D.; Chittum, Jessica R.; Akalin, Sehmuz; Schram, Asta B.; Fink, Jonathan; Schnittka, Christine; Evans, Michael A.; Brandt, Carol

    2015-01-01

    The primary purpose of this study was to examine the ways in which a 12-week after-school science and engineering program affected middle school students' motivation to engage in science and engineering activities. We used current motivation research and theory as a conceptual framework to assess 14 students' motivation through questionnaires,…

  9. Derivation of Huntington Disease affected Genea017 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea017 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1.27, demonstrated alkaline phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.

  10. How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body?

    PubMed Central

    Guilbaud, Axel; Niquet-Leridon, Celine; Boulanger, Eric; Tessier, Frederic J.

    2016-01-01

    The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients. The present article provides an overview of current dietary strategies tested either in vitro, in vivo or both to reduce the endogenous formation of AGEs and to limit exposure to food AGEs. PMID:28231179

  11. Derivation of FSHD1 affected human embryonic stem cell line Genea049.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea049 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 5 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 90% of cells expressed Nanog, 96% Oct4, 80% Tra1-60 and 99% SSEA4, gave a Pluritest Pluripotency score of 23.16, Novelty of 1.43 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  12. Copper, lead and zinc concentrations of human breast milk as affected by maternal dietary practices

    SciTech Connect

    Umoren, J.; Kies, C.

    1986-03-01

    Maternal dietary practices have been found to affect the concentrations of some nutrients in human breast milk. Lead toxicity is a concern in young children. Lead, copper and zinc are thought to compete for intestinal absorption sites. The objective of the current project was to compare copper, lead and zinc contents of breast milk from practicing lacto-vegetarian and omnivore, lactating women at approximately four months post-partum. Analyses were done by atomic absorption spectrophotometry using a carbon rod attachment. Copper concentrations were higher in milk samples from lacto-ovo-vegetarians. Milk samples from the omnivores had the highest lead and zinc concentrations. Lead and copper concentrations in milk were negatively correlated. The higher zinc concentrations in the milk of the omnivore women may have been related to better utilization of zinc from meat than from plant food sources.

  13. Some factors affecting the action of restriction endonucleases on human metaphase chromosomes.

    PubMed

    Mezzanotte, R; Ferrucci, L; Vanni, R; Sumner, A T

    1985-11-01

    We have investigated whether restriction endonucleases produce bands on human chromosomes by extracting DNA, using staining methods which are stoichiometric for DNA. Restriction enzymes that produce C-band patterns appear to remove DNA extensively from chromosome arms. In general, however, those restriction enzymes that produce G-bands do not extract DNA from chromosomes, and their effects are believed to be due to conformational change in the chromosomal DNA; in these cases, the chromosomal regions affected appear to be determined by the chromosome structure and not by the specificity of the enzyme. DNA loss from chromosomes due to digestion by restriction enzymes may in some cases be uniform, although a G-banding pattern is visible after Giemsa staining.

  14. Larval nutritional stress affects vector life history traits and human malaria transmission

    PubMed Central

    Vantaux, Amélie; Lefèvre, Thierry; Cohuet, Anna; Dabiré, Kounbobr Roch; Roche, Benjamin; Roux, Olivier

    2016-01-01

    Exposure to stress during an insect’s larval development can have carry-over effects on adult life history traits and susceptibility to pathogens. We investigated the effects of larval nutritional stress for the first time using field mosquito vectors and malaria parasites. In contrast to previous studies, we show that larval nutritional stress may affect human to mosquito transmission antagonistically: nutritionally deprived larvae showed lower parasite prevalence for only one gametocyte carrier; they also had lower fecundity. However, they had greater survival rates that were even higher when infected. When combining these opposing effects into epidemiological models, we show that larval nutritional stress induced a decrease in malaria transmission at low mosquito densities and an increase in transmission at high mosquito densities, whereas transmission by mosquitoes from well-fed larvae was stable. Our work underscores the importance of including environmental stressors towards understanding host–parasite dynamics to improve disease transmission models and control. PMID:27827429

  15. Larval nutritional stress affects vector life history traits and human malaria transmission.

    PubMed

    Vantaux, Amélie; Lefèvre, Thierry; Cohuet, Anna; Dabiré, Kounbobr Roch; Roche, Benjamin; Roux, Olivier

    2016-11-09

    Exposure to stress during an insect's larval development can have carry-over effects on adult life history traits and susceptibility to pathogens. We investigated the effects of larval nutritional stress for the first time using field mosquito vectors and malaria parasites. In contrast to previous studies, we show that larval nutritional stress may affect human to mosquito transmission antagonistically: nutritionally deprived larvae showed lower parasite prevalence for only one gametocyte carrier; they also had lower fecundity. However, they had greater survival rates that were even higher when infected. When combining these opposing effects into epidemiological models, we show that larval nutritional stress induced a decrease in malaria transmission at low mosquito densities and an increase in transmission at high mosquito densities, whereas transmission by mosquitoes from well-fed larvae was stable. Our work underscores the importance of including environmental stressors towards understanding host-parasite dynamics to improve disease transmission models and control.

  16. THE NATIONAL EXPOSURE RESEARCH LABORATORY'S CONSOLIDATED HUMAN ACTIVITY DATABASE

    EPA Science Inventory

    EPA's National Exposure Research Laboratory (NERL) has combined data from 12 U.S. studies related to human activities into one comprehensive data system that can be accessed via the Internet. The data system is called the Consolidated Human Activity Database (CHAD), and it is ...

  17. THE NATIONAL EXPOSURE RESEARCH LABORATORY'S COMPREHENSIVE HUMAN ACTIVITY DATABASE

    EPA Science Inventory

    EPA's National Exposure Research Laboratory (NERL) has combined data from nine U.S. studies related to human activities into one comprehensive data system that can be accessed via the world-wide web. The data system is called CHAD-Consolidated Human Activity Database-and it is ...

  18. Human multimedia display interface based on human activity recognition

    NASA Astrophysics Data System (ADS)

    Shang, Yiting; Lee, Eung-Joo

    2011-06-01

    In this paper, we will propose a Human Multimedia Display Interface. The interface uses the tracking of human hand movements to control the IP-TV. This paper presents an improved CAMSHIFT algorithm to control an IP-TV system. The CAMSHIFT algorithm (Continuously Adaptive MeanShift) is a method of using color information[1]. It can do tracking with a specific color of the target. In some typical environmental constraints, it can obtain good tracking performance. However, as the question of noise, large area similar to the color interference and so on, only by CAM-SHIFT algorithm it is not competent. Against these issues we propose an improved CAMSHIFT algorithm[2].

  19. Temporal behaviour profiles of Mus musculus in nature are affected by population activity.

    PubMed

    Robbers, Yuri; Koster, Eva A S; Krijbolder, Doortje I; Ruijs, Amanda; van Berloo, Sander; Meijer, Johanna H

    2015-02-01

    Animals have circadian clocks that govern their activity pattern, resulting in 24h rhythms in physiology and behaviour. Under laboratory conditions, light is the major external signal that affects temporal patterns in behaviour, and Mus musculus is strictly nocturnal in its behaviour. In the present study we questioned whether under natural conditions, environmental factors other than light affect the temporal profile of mice. In order to test this, we investigated the activity patterns of free-ranging M. musculus in a natural habitat, using sensors and a camera integrated into a recording unit that the mice could freely enter and leave. Our data show that mice have seasonal fluctuations in activity duration (6.7±0.82 h in summer, 11.3±1.80 h in winter). Furthermore, although primarily nocturnal, wild mice also exhibit daytime activity from spring until late autumn. A multivariate analysis revealed that the major factor correlating with increased daytime activity was population activity, defined as the number of visits to the recording site. Day length had a small but significant effect. Further analysis revealed that the relative population activity (compared to the past couple of days) is a better predictor of daytime activity than absolute population activity. Light intensity and temperature did not have a significant effect on daytime activity. The amount of variance explained by external factors is 51.9%, leaving surprisingly little unexplained variance that might be attributed to the internal clock. Our data further indicate that mice determine population activity by comparing a given night with the preceding 2-7 nights, a time frame suggesting a role for olfactory cues. We conclude that relative population activity is a major factor controlling the temporal activity patterns of M. musculus in an unrestricted natural population.

  20. Amyloid precursor protein (APP) affects global protein synthesis in dividing human cells.

    PubMed

    Sobol, Anna; Galluzzo, Paola; Liang, Shuang; Rambo, Brittany; Skucha, Sylvia; Weber, Megan J; Alani, Sara; Bocchetta, Maurizio

    2015-05-01

    Hypoxic non-small cell lung cancer (NSCLC) is dependent on Notch-1 signaling for survival. Targeting Notch-1 by means of γ-secretase inhibitors (GSI) proved effective in killing hypoxic NSCLC. Post-mortem analysis of GSI-treated, NSCLC-burdened mice suggested enhanced phosphorylation of 4E-BP1 at threonines 37/46 in hypoxic tumor tissues. In vitro dissection of this phenomenon revealed that Amyloid Precursor Protein (APP) inhibition was responsible for a non-canonical 4E-BP1 phosphorylation pattern rearrangement-a process, in part, mediated by APP regulation of the pseudophosphatase Styx. Upon APP depletion we observed modifications of eIF-4F composition indicating increased recruitment of eIF-4A to the mRNA cap. This phenomenon was supported by the observation that cells with depleted APP were partially resistant to silvestrol, an antibiotic that interferes with eIF-4A assembly into eIF-4F complexes. APP downregulation in dividing human cells increased the rate of global protein synthesis, both cap- and IRES-dependent. Such an increase seemed independent of mTOR inhibition. After administration of Torin-1, APP downregulation and Mechanistic Target of Rapamycin Complex 1 (mTORC-1) inhibition affected 4E-BP1 phosphorylation and global protein synthesis in opposite fashions. Additional investigations indicated that APP operates independently of mTORC-1. Key phenomena described in this study were reversed by overexpression of the APP C-terminal domain. The presented data suggest that APP may be a novel regulator of protein synthesis in dividing human cells, both cancerous and primary. Furthermore, APP appears to affect translation initiation using mechanisms seemingly dissimilar to mTORC-1 regulation of cap-dependent protein synthesis.

  1. Argon does not affect cerebral circulation or metabolism in male humans

    PubMed Central

    Kazmaier, Stephan; Hoeks, Sanne Elisabeth; Stolker, Robert Jan; Coburn, Marc; Weyland, Andreas

    2017-01-01

    Objective Accumulating data have recently underlined argon´s neuroprotective potential. However, to the best of our knowledge, no data are available on the cerebrovascular effects of argon (Ar) in humans. We hypothesized that argon inhalation does not affect mean blood flow velocity of the middle cerebral artery (Vmca), cerebral flow index (FI), zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe), resistance area product (RAP) and the arterio-jugular venous content differences of oxygen (AJVDO2), glucose (AJVDG), and lactate (AJVDL) in anesthetized patients. Materials and methods In a secondary analysis of an earlier controlled cross-over trial we compared parameters of the cerebral circulation under 15 minutes exposure to 70%Ar/30%O2 versus 70%N2/30%O2 in 29 male patients under fentanyl-midazolam anaesthesia before coronary surgery. Vmca was measured by transcranial Doppler sonography. ZFP and RAP were estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. CPPe was calculated as the difference between mean arterial pressure and ZFP. AJVDO2, AJVDG and AJVDL were calculated as the differences in contents between arterial and jugular-venous blood of oxygen, glucose, and lactate. Statistical analysis was done by t-tests and ANOVA. Results Mechanical ventilation with 70% Ar did not cause any significant changes in mean arterial pressure, Vmca, FI, ZFP, CPPe, RAP, AJVDO2, AJVDG, and AJVDL. Discussion Short-term inhalation of 70% Ar does not affect global cerebral circulation or metabolism in male humans under general anaesthesia. PMID:28207907

  2. Activities of Human Gene Nomenclature Committee

    SciTech Connect

    2002-07-16

    The objective of this project, shared between NIH and DOE, has been and remains to enable the medical genetics communities to use common names for genes that are discovered by different gene hunting groups, in different species. This effort provides consistent gene nomenclature and approved gene symbols to the community at large. This contributes to a uniform and consistent understanding of genomes, particularly the human as well as functional genomics based on comparisons between homologous genes in related species (human and mice).

  3. Does human proximity affect antibody prevalence in marine-foraging river otters (Lontra canadensis)?

    PubMed

    Gaydos, Joseph K; Conrad, Patricia A; Gilardi, Kirsten V K; Blundell, Gail M; Ben-David, Merav

    2007-01-01

    The investigation of diseases of free-ranging river otters (Lontra canadensis) is a primary conservation priority for this species; however, very little is known about diseases of river otters that forage in marine environments. To identify and better understand pathogens that could be important to marine-foraging river otters, other wildlife species, domestic animals, and humans and to determine if proximity to human population could be a factor in disease exposure, serum samples from 55 free-ranging marine-foraging river otters were tested for antibodies to selected pathogens. Thirty-five animals were captured in Prince William Sound, Alaska (USA), an area of low human density, and 20 were captured in the San Juan Islands, Washington State (USA), an area characterized by higher human density. Of 40 river otters tested by indirect immunofluorescent antibody test, 17.5% were seropositive (titer > or =320) for Toxoplasma gondii. All positive animals came from Washington. Of 35 river otters tested for antibodies to Leptospira interrogans using the microscopic agglutination test, 10 of 20 (50%) from Washington were seropositive (titer > or =200). None of the 15 tested animals from Alaska were positive. Antibodies to Neospora caninum (n=40), Sarcocystis neurona (n=40), Brucella abortus (n=55), avian influenza (n=40), canine distemper virus (n=55), phocine distemper virus (n=55), dolphin morbillivirus (n=55), porpoise morbillivirus (n=55), and Aleutian disease parvovirus (n=46) were not detected. Identifying exposure to T. gondii and L. interrogans in otters from Washington State but not in otters from Alaska suggests that living proximal to higher human density and its associated agricultural activities, domestic animals, and rodent populations could enhance river otter exposure to these pathogens.

  4. Lethal Factor Active-Site Mutations Affect Catalytic Activity In Vitro

    PubMed Central

    Hammond, S. E.; Hanna, P. C.

    1998-01-01

    The lethal factor (LF) protein of Bacillus anthracis lethal toxin contains the thermolysin-like active-site and zinc-binding consensus motif HEXXH (K. R. Klimpel, N. Arora, and S. H. Leppla, Mol. Microbiol. 13:1093–1100, 1994). LF is hypothesized to act as a Zn2+ metalloprotease in the cytoplasm of macrophages, but no proteolytic activities have been previously shown on any target substrate. Here, synthetic peptides are hydrolyzed by LF in vitro. Mass spectroscopy and peptide sequencing of isolated cleavage products separated by reverse-phase high-pressure liquid chromatography indicate that LF seems to prefer proline-containing substrates. Substitution mutations within the consensus active-site residues completely abolish all in vitro catalytic functions, as does addition of 1,10-phenanthroline, EDTA, and certain amino acid hydroxamates, including the novel zinc metalloprotease inhibitor ZINCOV. In contrast, the protease inhibitors bestatin and lysine CMK, previously shown to block LF activity on macrophages, did not block LF activity in vitro. These data provide the first direct evidence that LF may act as an endopeptidase. PMID:9573135

  5. Dopamine Transporter Gene Variant Affecting Expression in Human Brain is Associated with Bipolar Disorder

    PubMed Central

    Pinsonneault, Julia K; Han, Dawn D; Burdick, Katherine E; Kataki, Maria; Bertolino, Alessandro; Malhotra, Anil K; Gu, Howard H; Sadee, Wolfgang

    2011-01-01

    The gene encoding the dopamine transporter (DAT) has been implicated in CNS disorders, but the responsible polymorphisms remain uncertain. To search for regulatory polymorphisms, we measured allelic DAT mRNA expression in substantia nigra of human autopsy brain tissues, using two marker SNPs (rs6347 in exon 9 and rs27072 in the 3′-UTR). Allelic mRNA expression imbalance (AEI), an indicator of cis-acting regulatory polymorphisms, was observed in all tissues heterozygous for either of the two marker SNPs. SNP scanning of the DAT locus with AEI ratios as the phenotype, followed by in vitro molecular genetics studies, demonstrated that rs27072 C>T affects mRNA expression and translation. Expression of the minor T allele was dynamically regulated in transfected cell cultures, possibly involving microRNA interactions. Both rs6347 and rs3836790 (intron8 5/6 VNTR) also seemed to affect DAT expression, but not the commonly tested 9/10 VNTR in the 3′UTR (rs28363170). All four polymorphisms (rs6347, intron8 5/6 VNTR, rs27072 and 3′UTR 9/10 VNTR) were genotyped in clinical cohorts, representing schizophrenia, bipolar disorder, depression, and controls. Only rs27072 was significantly associated with bipolar disorder (OR=2.1, p=0.03). This result was replicated in a second bipolar/control population (OR=1.65, p=0.01), supporting a critical role for DAT regulation in bipolar disorder. PMID:21525861

  6. Human resources management and firm performance: The differential role of managerial affective and continuance commitment.

    PubMed

    Gong, Yaping; Law, Kenneth S; Chang, Song; Xin, Katherine R

    2009-01-01

    In this study, the authors developed a dual-concern (i.e., maintenance and performance) model of human resources (HR) management. The authors identified commonly examined HR practices that apply to the middle manager level and classified them into the maintenance- and performance-oriented HR subsystems. The authors found support for the 2-factor model on the basis of responses from 2,148 managers from 463 firms operating in China. Regression results indicate that the performance-oriented HR subsystems had a positive relationship with firm performance and that the relationship was mediated by middle managers' affective commitment to the firm. The maintenance-oriented HR subsystems had a positive relationship with middle managers' continuance commitment but not with their affective commitment and firm performance. This study contributes to the understanding of how HR practices relate to firm performance and offers an improved test of the argument that valuable and firm-specific HR provide a source of competitive advantage. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  7. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    PubMed

    Miller, James R C; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J

    2015-01-01

    Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  8. Bright morning light advances the human circadian system without affecting NREM sleep homeostasis.

    PubMed

    Dijk, D J; Beersma, D G; Daan, S; Lewy, A J

    1989-01-01

    Eight male subjects were exposed to either bright light or dim light between 0600 and 0900 h for 3 consecutive days each. Relative to the dim light condition, the bright light treatment advanced the evening rise in plasma melatonin and the time of sleep termination (sleep onset was held constant) for an average approximately 1 h. The magnitude of the advance of the plasma melatonin rise was dependent on its phase in dim light. The reduction in sleep duration was at the expense of rapid-eye-movement (REM) sleep. Spectral analysis of the sleep electroencephalogram (EEG) revealed that the advance of the circadian pacemaker did not affect EEG power densities between 0.25 and 15.0 Hz during either non-REM or REM sleep. The data show that shifting the human circadian pacemaker by 1 h does not affect non-REM sleep homeostasis. These findings are in accordance with the predictions of the two-process model of sleep regulation.

  9. Structure-activity relationship of novel menaquinone-4 analogues: modification of the side chain affects their biological activities.

    PubMed

    Suhara, Yoshitomo; Hanada, Norika; Okitsu, Takashi; Sakai, Miho; Watanabe, Masato; Nakagawa, Kimie; Wada, Akimori; Takeda, Kazuyoshi; Takahashi, Kazuhiko; Tokiwa, Hiroaki; Okano, Toshio

    2012-02-23

    We synthesized new vitamin K analogues with demethylation or reduction of the double bonds of the side chain of menaquinone-4 (MK-4) and evaluated their SXR-mediated transcriptional activity as well as the extent of their conversion to MK-4. The results indicated that the analogue with the methyl group deleted at the 7' site of the side chain part affected conversion activity to MK-4. In contrast, a decrease in the number of the double bonds in the side chain moiety appeared to decrease the SXR-mediated transcriptional activity.

  10. Plant material as bioaccumulator of arsenic in soils affected by mining activities

    NASA Astrophysics Data System (ADS)

    Martínez-López, Salvadora; Martínez-Sánchez, Maria Jose; García-Lorenzo, Maria Luz; Pérez-Sirvent, Carmen

    2010-05-01

    Heavy metal contamination is an important environmental problem, since the metals are harmful to humans, animals and tend to bioaccumulate in the food chain. The aim of this study was to determine the total concentration of As, As (III) and As(V) in soil samples, leaves and roots of plant material, growing in a mining area in Spain (Murcia). Ditichia viscosa was used as the plant of reference. The concentrations of bioavailable As in plant samples were calculated by different soil chemical extraction methods; deionized water, 0.5N NaHCO3 (Olsen extraction), oxidizable medium, 0.5 HCl, 0.05M (NH4)2SO4, 0.005M DTPA and Mehra-Jackson extraction. For this study, fourteen samples were collected in the surrounding area of Sierra Minera and Portman Bay (Murcia, SE Spain). Samples were air dried and sieved to < 2mm for general analytical determinations. To determine the As content, soil samples were first ground to a fine powder using an agate ball mill. Fresh vegetable samples were separated into root and aboveground biomass and then lyophilized. Arsenic levels were obtained by using atomic fluorescence spectrometry with an automated continuous flow hydride generation (HG-AFS) spectrometer. Samples showed pH average values close to neutrality. Most samples showed a very low organic matter percentage. Electrical conductivity and calcium carbonate content were considerably low in most samples. The mineralogical analysis showed that the main minerals were quartz, muscovite, kaolinite and illite, while the minority minerals were alteration products derived of mining activities (iron oxides and hydroxides, siderite, jarosite and gypsum), calcite and feldspars. Although the plants do not absorb arsenic in the same proportion, the results suggest that a good relationship exists between the total content of As in soil and the total content in plant. The results showed that the arsenic content in roots was positively correlated with the oxidizable-organic matter and sulfides

  11. The absence of numbers to express the amount may affect delay discounting with humans.

    PubMed

    Reyes-Huerta, Hugo E; Dos Santos, Cristiano V

    2016-09-01

    Human delay discounting is usually studied with experimental protocols that use symbols to express delay and amount. In order to further understand discounting, we evaluated whether the absence of numbers to represent reward amounts affects discount rate in general, and whether the magnitude effect is generalized to nonsymbolic situations in particular. In Experiment 1, human participants were exposed to a delay-discounting task in which rewards were presented using dots to represent monetary rewards (nonsymbolic); under this condition the magnitude effect did not occur. Nevertheless, the magnitude effect was observed when equivalent reward amounts were presented using numbers (symbolic). Moreover, in estimation tasks, magnitude increments produced underestimation of large amounts. In Experiment 2, participants were exposed only to the nonsymbolic discounting task and were required to estimate reward amounts in each trial. Consistent with Experiment 1, the absence of numbers representing reward amounts produced similar discount rates of small and large rewards. These results suggest that value of nonsymbolic rewards is a nonlinear function of amount and that value attribution depends on perceived difference between the immediate and the delayed nonsymbolic rewards.

  12. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria

    PubMed Central

    Shapiro, Lillian L. M.; Murdock, Courtney C.; Jacobs, Gregory R.; Thomas, Rachel J.; Thomas, Matthew B.

    2016-01-01

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260–330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  13. Individual differences in behavioral activation and cardiac vagal control influence affective startle modification.

    PubMed

    Yang, Xiao; Friedman, Bruce H

    2017-04-01

    The startle response (SR) has a close relationship with stress responses. Startle modification (SRM) has been widely used to study stress disorders (e.g., posttraumatic stress disorder). The framework of the behavioral inhibition and activation systems (BIS/BAS) has been thought to correspond with withdrawal and approach motivational processes underlying affective SRM and can influence stress reactivity. Vagally-mediated cardiac activity as indexed by heart rate variability (HRV) has been associated with SRM and regulatory processes during stress. In the present study, the influence of individual differences in the BIS/BAS and resting HRV on affective SRM were examined. Eighty-six subjects viewed affective pictures while acoustic SR stimuli were delivered. Individual differences in motivation were measured by the BIS/BAS scales. The magnitude of SR was assessed as electromyographic activity of the SR eyeblink during pictures of different valences. Resting HRV was derived from electrocardiography. In contrast to previous studies, the present results showed that startle inhibition and potentiation were related to BAS and HRV, but not to BIS. There was also an interaction of BAS and HRV, indicating that the relationship between HRV and SRM strengthened as BAS scores decreased. The present findings suggest that BAS may relate to both withdrawal and approach, and trait stress reactivity is influenced by BAS and cardiac vagal activity. In addition, BAS moderates the relationship between cardiac vagal activity and SRM. These findings have both theoretical and practical implications for the study of SRM, stress disorders, and health.

  14. Water quality degradation effects on freshwater availability: Impacts to human activities

    USGS Publications Warehouse

    Peters, N.E.; Meybeck, Michel

    2000-01-01

    The quality of freshwater at any point on the landscape reflects the combined effects of many processes along water pathways. Human activities on all spatial scales affect both water quality and quantity. Alteration of the landscape and associated vegetation has not only changed the water balance, but typically has altered processes that control water quality. Effects of human activities on a small scale are relevant to an entire drainage basin. Furthermore, local, regional, and global differences in climate and water flow are considerable, causing varying effects of human activities on land and water quality and quantity, depending on location within a watershed, geology, biology, physiographic characteristics, and climate. These natural characteristics also greatly control human activities, which will, in turn, modify (or affect) the natural composition of water. One of the most important issues for effective resource management is recognition of cyclical and cascading effects of human activities on the water quality and quantity along hydrologic pathways. The degradation of water quality in one part of a watershed can have negative effects on users downstream. Everyone lives downstream of the effects of some human activity. An extremely important factor is that substances added to the atmosphere, land, and water generally have relatively long time scales for removal or clean up. The nature of the substance, including its affinity for adhering to soil and its ability to be transformed, affects the mobility and the time scale for removal of the substance. Policy alone will not solve many of the degradation issues, but a combination of policy, education, scientific knowledge, planning, and enforcement of applicable laws can provide mechanisms for slowing the rate of degradation and provide human and environmental protection. Such an integrated approach is needed to effectively manage land and water resources.

  15. Oral administration of stavudine induces hyperalgesia without affecting activity in rats.

    PubMed

    Weber, Juliane; Mitchell, Duncan; Kamerman, Peter R

    2007-12-05

    We have investigated whether long-term oral administration of the nucleoside reverse transcriptase inhibitor (NRTI) stavudine affects nociception in Sprague-Dawley rats, and whether any changes of nociception are accompanied by deterioration in activity and appetite. Stavudine (50 mg kg(-1)) was administered to rats orally once daily for six weeks in gelatine cubes. Mechanical hyperalgesia of the tail was assessed using a bar algometer, and thermal hyperalgesia by tail immersion in 49 degrees C water. Withdrawal latencies were compared to those of rats receiving placebo gelatine cubes. Withdrawal latencies to the noxious thermal challenge were not affected by stavudine, but those to the mechanical challenge were significantly decreased in rats receiving stavudine, compared to rats receiving placebo, from week three to week six of drug administration (P<0.05, ANCOVA with Newman Keuls post-hoc comparisons). The overall condition of the rats was assessed by recording daily voluntary wheel running distance and maximum running speed, food intake and body mass. Daily stavudine administration did not adversely affect voluntary running activity, appetite or growth. We have shown that long-term daily oral administration of the NRTI stavudine results in mechanical hyperalgesia in rats within three weeks without affecting appetite, growth and physical activity.

  16. Physical Activity, Mind Wandering, Affect, and Sleep: An Ecological Momentary Assessment

    PubMed Central

    Mackenzie, Michael; Roberts, Sarah; Crato, Ines; Ehlers, Diane; McAuley, Edward

    2016-01-01

    Background A considerable portion of daily thought is spent in mind wandering. This behavior has been related to positive (eg, future planning, problem solving) and negative (eg, unhappiness, impaired cognitive performance) outcomes. Objective Based on previous research suggesting future-oriented (ie, prospective) mind wandering may support autobiographical planning and self-regulation, this study examined associations between hourly mind wandering and moderate-to-vigorous physical activity (MVPA), and the impact of affect and daily sleep on these relations. Methods College-aged adults (N=33) participated in a mobile phone-delivered ecological momentary assessment study for 1 week. Sixteen hourly prompts assessing mind wandering and affect were delivered daily via participants’ mobile phones. Perceived sleep quality and duration was assessed during the first prompt each day, and participants wore an ActiGraph accelerometer during waking hours throughout the study week. Results Study findings suggest present-moment mind wandering was positively associated with future MVPA (P=.03), and this relationship was moderated by affective state (P=.04). Moreover, excessive sleep the previous evening was related to less MVPA across the following day (P=.007). Further, mind wandering was positively related to activity only among those who did not oversleep (P=.007). Conclusions Together, these results have implications for multiple health behavior interventions targeting physical activity, affect, and sleep. Researchers may also build on this work by studying these relationships in the context of other important behaviors and psychosocial factors (eg, tobacco use, depression, loneliness). PMID:27580673

  17. Human Activity Recognition in AAL Environments Using Random Projections

    PubMed Central

    Damaševičius, Robertas; Vasiljevas, Mindaugas; Šalkevičius, Justas; Woźniak, Marcin

    2016-01-01

    Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject's body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL), for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD) data are presented. PMID:27413392

  18. Human Activity Recognition in AAL Environments Using Random Projections.

    PubMed

    Damaševičius, Robertas; Vasiljevas, Mindaugas; Šalkevičius, Justas; Woźniak, Marcin

    2016-01-01

    Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject's body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL), for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD) data are presented.

  19. Tadpole swimming performance and activity affected by acute exposure to sublethal levels of carbaryl

    USGS Publications Warehouse

    Bridges, C.M.

    1997-01-01

    General activity and swimming performance (i.e., sprint speed and distance) of plains leopard frog tadpoles (Rana blairi) were examined after acute exposure to three sublethal concentrations of carbaryl (3.5, 5.0, and 7.2 mg/L). Both swimming performance and spontaneous swimming activity are important for carrying out life history functions (e.g., growth and development) and for escaping from predators. Measured tadpole activity diminished by nearly 90% at 3.5 mg/L carbaryl and completely ceased at 7.2 mg/L. Sprint speed and sprint distance also decreased significantly following exposure. Carbaryl affected both swimming performance and activity after just 24 h, suggesting that 24 h may be an adequate length of exposure to determine behavioral effects on tadpoles. Slight recovery of activity levels was noted at 24 and 48 h post-exposure; no recovery of swimming performance was observed. Reduction in activity and swimming performance may result in increased predation rates and, because activity is closely associated with feeding, may result in slowed growth leading to a failure to emerge before pond drying or an indirect reduction in adult fitness. Acute exposure to sublethal toxicants such as carbaryl may not only affect immediate survival of tadpoles but also impact critical life history functions and generate changes at the local population level.

  20. Prion Protein M129V Polymorphism Affects Retrieval-Related Brain Activity

    ERIC Educational Resources Information Center

    Buchmann, Andreas; Mondadori, Christian R. A.; Hanggi, Jurgen; Aerni, Amanda; Vrticka, Pascal; Luechinger, Roger; Boesiger, Peter; Hock, Christoph; Nitsch, Roger M.; de Quervain, Dominique J.-F.; Papassotiropoulos, Andreas; Henke, Katharina

    2008-01-01

    The prion protein Met129Val polymorphism has recently been related to human long-term memory with carriers of either the 129[superscript MM] or the 129[superscript MV] genotype recalling 17% more words than 129[superscript VV] carriers at 24 h following learning. Here, we sampled genotype differences in retrieval-related brain activity at 30 min…

  1. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers

    NASA Astrophysics Data System (ADS)

    Blarquez, Olivier; Ali, Adam A.; Girardin, Martin P.; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-09-01

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees.

  2. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers

    PubMed Central

    Blarquez, Olivier; Ali, Adam A.; Girardin, Martin P.; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-01-01

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees. PMID:26330162

  3. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials.

    PubMed

    Jin, Xia; Morgan, Cecilia; Yu, Xuesong; DeRosa, Stephen; Tomaras, Georgia D; Montefiori, David C; Kublin, James; Corey, Larry; Keefer, Michael C

    2015-05-11

    Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8-17.8%) and 37.7% (95% CI: 31.9-43.8%) of vaccine recipients, respectively. Three vaccinations (vs. 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower body mass index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials.

  4. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers.

    PubMed

    Blarquez, Olivier; Ali, Adam A; Girardin, Martin P; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-09-02

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees.

  5. Thiazide diuretics affect osteocalcin production in human osteoblasts at the transcription level without affecting vitamin D3 receptors.

    PubMed

    Lajeunesse, D; Delalandre, A; Guggino, S E

    2000-05-01

    Besides their natriuretic and calciuretic effect, thiazide diuretics have been shown to decrease bone loss rate and improve bone mineral density. Clinical evidence suggests a specific role of thiazides on osteoblasts, because it reduces serum osteocalcin (OC), an osteoblast-specific protein, yet the mechanisms implicated are unknown. We therefore investigated the role of hydrochlorothiazide (HCTZ) on OC production by the human osteoblast-like cell line MG-63. HCTZ dose-dependently (1-100 microM) inhibited 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced OC release by these cells (maximal effect, -40-50% and p < 0.005 by analysis of variance [ANOVA]) as measured by ELISA. This effect of HCTZ on OC release was caused by a direct effect on OC gene expression because Northern blot analysis revealed that OC messenger RNA (mRNA) levels were reduced in the presence of increasing doses of the diuretic (-47.2+/-4.0%; p < 0.0001 by paired ANOVA with 100 microM 13.6+/-0.49 pmol/mg protein/15 minutes; p < 0.05) in MG-63 cells. Reducing extracellular Ca2+ concentration with 0.5 mM EDTA or 0.5 mM ethylene glycol-bis(beta-amino ethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) only partly prevented the inhibitory effect of the diuretic on OC secretion (maximal effect, -22.5+/-6.9%), suggesting that thiazide-dependent Ca2+ influx is not sufficient to elicit the inhibition of OC secretion. Because OC production is strictly dependent on the presence of 1,25(OH)2D3 in human osteoblasts, we next evaluated the possible role of HCTZ on vitamin D3 receptors (VDR) at the mRNA and protein levels. Both Northern and Western blot analyses showed no effect of HCTZ (1-100 microM) on VDR levels. The presence of EGTA in the culture media reduced slightly the VDR mRNA levels under basal condition but this was not modified in the presence of increasing levels of HCTZ. The OC gene promoter also is under the control of transcription factors such as Yin Yang 1 (YY1) and cFOS. Western blot analysis revealed

  6. Voltage-activated proton current in eosinophils from human blood.

    PubMed Central

    Gordienko, D V; Tare, M; Parveen, S; Fenech, C J; Robinson, C; Bolton, T B

    1996-01-01

    negative potentials and enhancement of maximum conductance (gH,max). The proton current recorded in eosinophils was significantly augmented under conditions of elevated cytosolic free calcium concentration ([Ca2+]i). The threshold level of [Ca2+]i associated with this effect lay between 0.1 and 1 microM and was not measurably affected by cytosolic acidification. 7. Eosinophils from human blood possess a voltage-dependent H+ conductance (gH) which normally allows protons to move outwards only; raising [Ca2+]i was associated with augmentation of gH and intracellular acidification or arachidonate shifted its activation range negatively towards physiological potentials. PMID:8910217

  7. Disrupting Mitochondrial–Nuclear Coevolution Affects OXPHOS Complex I Integrity and Impacts Human Health

    PubMed Central

    Gershoni, Moran; Levin, Liron; Ovadia, Ofer; Toiw, Yasmin; Shani, Naama; Dadon, Sara; Barzilai, Nir; Bergman, Aviv; Atzmon, Gil; Wainstein, Julio; Tsur, Anat; Nijtmans, Leo; Glaser, Benjamin; Mishmar, Dan

    2014-01-01

    The mutation rate of the mitochondrial DNA (mtDNA), which is higher by an order of magnitude as compared with the nuclear genome, enforces tight mitonuclear coevolution to maintain mitochondrial activities. Interruption of such coevolution plays a role in interpopulation hybrid breakdown, speciation events, and disease susceptibility. Previously, we found an elevated amino acid replacement rate and positive selection in the nuclear DNA-encoded oxidative phosphorylation (OXPHOS) complex I subunit NDUFC2, a phenomenon important for the direct interaction of NDUFC2 with the mtDNA-encoded complex I subunit ND4. This finding underlines the importance of mitonuclear coevolution to physical interactions between mtDNA and nuclear DNA-encoded factors. Nevertheless, it remains unclear whether this interaction is important for the stability and activity of complex I. Here, we show that siRNA silencing of NDUFC2 reduced growth of human D-407 retinal pigment epithelial cells, significantly diminished mitochondrial membrane potential, and interfered with complex I integrity. Moreover, site-directed mutagenesis of a positively selected amino acid in NDUFC2 significantly interfered with the interaction of NDUFC2 with its mtDNA-encoded partner ND4. Finally, we show that a genotype combination involving this amino acid (NDUFC2 residue 46) and the mtDNA haplogroup HV likely altered susceptibility to type 2 diabetes mellitus in Ashkenazi Jews. Therefore, mitonuclear coevolution is important for maintaining mitonuclear factor interactions, OXPHOS, and for human health. PMID:25245408

  8. Contractility and calcium signaling of human myometrium are profoundly affected by cholesterol manipulation: implications for labor?

    PubMed

    Jie Zhang; Kendrick, Annabelle; Quenby, Siobhan; Wray, Susan

    2007-07-01

    The authors elucidate cholesterol's effect on human uterine contractility and calcium signaling to test the hypotheses that elevation of cholesterol decreases uterine activity and that oxytocin cannot augment contraction when cholesterol is elevated. The effects of cholesterol extraction with methyl beta-cyclodextrin and enrichment with low-density lipoproteins and cholesterol on contractile activity and intracellular calcium signaling in spontaneous or oxytocin-stimulated myometrium are determined. Force occurring spontaneously and with oxytocin is significantly increased by cholesterol extraction. Cholesterol enrichment profoundly inhibits force production in a dose-dependent manner and could reverse the effects of cholesterol extraction. Qualitatively similar results are found for nonpregnant and pregnant laboring and non-laboring myometrium. These contractile changes are related to changes in intracellular Ca2+ . Thus, elevated cholesterol is deleterious to contractility and Ca2+ signaling in human myometrium. Cholesterol may contribute to uterine quiescence but could cause difficulties in labor in obese/dyslipidemic women, consistent with their increased cesarean delivery rates.

  9. Immunogenetic factors affecting susceptibility of humans and rodents to hantaviruses and the clinical course of hantaviral disease in humans.

    PubMed

    Charbonnel, Nathalie; Pagès, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti

    2014-05-26

    We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives.

  10. Sex and storage affect cholinesterase activity in blood plasma of Japanese quail

    USGS Publications Warehouse

    Hill, E.F.

    1989-01-01

    Freezing at -25?C had confounding effects on cholinesterase (ChE) activity in blood plasma from breeding female quail, but did not affect ChE activity in plasma from males. Plasma ChE activity of control females increased consistently during 28 days of storage while both carbamate- and cidrotophos-inhibited ChE decreased. Refrigeration of plasma at 4?C for 2 days had little effect of ChE activity. Plasma ChE activity was averaged about 34% higher in breeding males than in females. Extreme caution should be exercised in use of blood plasma for evaluation of anti ChE exposure in free-living birds.

  11. Reward expectancy-related prefrontal neuronal activities: are they neural substrates of "affective" working memory?

    PubMed

    Watanabe, Masataka; Hikosaka, Kazuo; Sakagami, Masamichi; Shirakawa, Shu-ichiro

    2007-01-01

    Primate prefrontal delay neurons are involved in retaining task-relevant cognitive information in working memory (WM). Recent studies have also revealed primate prefrontal delay neurons that are related to reward/omission-of-reward expectancy. Such reward-related delay activities might constitute "affective WM" (Davidson, 2002). "Affective" and "cognitive" WM are both concerned with representing not what is currently being presented, but rather what was presented previously or might be presented in the future. However, according to the original and widely accepted definition, WM is the "temporary storage and manipulation of information for complex cognitive tasks". Reward/omission-of-reward expectancy-related neuronal activity is neither prerequisite nor essential for accurate task performance; thus, such activity is not considered to comprise the neural substrates of WM. Also, "affective WM" might not be an appropriate usage of the term "WM". We propose that WM- and reward/omission-of-reward expectancy-related neuronal activity are concerned with representing which response should be performed in order to attain a goal (reward) and the goal of the response, respectively. We further suggest that the prefrontal cortex (PFC) plays a crucial role in the integration of cognitive (for example, WM-related) and motivational (for example, reward expectancy-related) operations for goal-directed behaviour. The PFC could then send this integrated information to other brain areas to control the behaviour.

  12. Biofidelic Human Activity Modeling and Simulation with Large Variability

    DTIC Science & Technology

    2014-11-25

    capture data to replicate a human activity in 3D space. Since technologies for simultaneously capturing human motion and dynamic shapes are not yet ready...for practical use, a motion capture system can be used to capture markers on the body during motion and a 3D body scanner can be used to capture the...animation-capable model that can replicate a human activity in 3D space with the true shape and true motion of a human. Using this approach, a model

  13. Activation of the δ-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration

    PubMed Central

    Bigliardi, P L; Neumann, C; Teo, Y L; Pant, A; Bigliardi-Qi, M

    2015-01-01

    BACKGROUND AND PURPOSE In addition to its analgesic functions, the peripheral opioid receptor system affects skin homeostasis by influencing cell differentiation, migration and adhesion; also, wound healing is altered in δ-opioid receptor knockout mice (DOPr–/–). Hence, we investigated δ-opioid receptor effects on the expression of several proteins of the desmosomal junction complex and on the migratory behaviour of keratinocytes. EXPERIMENTAL APPROACH Expression levels of desmosomal cadherins in wild-type and DOPr–/– mice, and the morphology of intercellular adhesion in human keratinocytes were analysed by immunofluorescence. To investigate the δ-opioid receptor activation pathway, protein expression was studied using Western blot and its effect on cellular migration determined by in vitro live cell migration recordings from human keratinocytes. KEY RESULTS Expression of the desmosomal cadherins, desmogleins 1 and 4, was up-regulated in skin from DOPr–/– mice, and down-regulated in δ-opioid receptor-overexpressing human keratinocytes. The localization of desmoplakin expression was rearranged from linear arrays emanating from cell borders to puncta in cell periphery, resulting in less stable intercellular adhesion. Migration and wound recovery were enhanced in human keratinocyte monolayers overexpressing δ-opioid receptors in vitro. These δ-opioid receptor effects were antagonized by specific PKCα/β inhibition indicating they were mediated through the PKC signalling pathway. Finally, cells overexpressing δ-opioid receptors developed characteristically long but undirected protrusions containing filamentous actin and δ-opioid receptors, indicating an enhanced migratory phenotype. CONCLUSION AND IMPLICATIONS Opioid receptors affect intercellular adhesion and wound healing mechanisms, underlining the importance of a cutaneous neuroendocrine system in wound healing and skin homeostasis. LINKED ARTICLES This article is part of a themed section on

  14. The oxidation of methionine-54 of epoetinum alfa does not affect molecular structure or stability, but does decrease biological activity.

    PubMed

    Labrenz, Steven R; Calmann, Melissa A; Heavner, George A; Tolman, Glen

    2008-01-01

    Erythropoietin therapy is used to treat severe anemia in renal failure and chemotherapy patients. One of these therapies based on recombinant human erythropoietin is marketed under the trade name of EPREX and utilizes epoetinum alfa as the active pharmaceutical ingredient. The effect of oxidation of methionine-54 on the structure and stability of the erythropoietin molecule has not been directly tested. We have observed partial and full chemical oxidation of methionine-54 to methionine-54 sulfoxide, accomplished using tert-Butylhydroperoxide and hydrogen peroxide, respectively. A blue shift in the fluorescence center of spectral mass wavelength was observed as a linear response to the level of methionine sulfoxide in the epoetinum alfa molecule, presumably arising from a local change in the environment near tryptophan-51, as supported by potassium iodide quenching studies. Circular dichroism studies demonstrated no change in the folded structure of the molecule with methionine oxidation. The thermal unfolding profiles of partial and completely oxidized epoetinum alfa overlap, with a T(m) of 49.5 degrees C across all levels of methionine sulfoxide content. When the protein was tested for activity, a decrease in biological activity was observed, correlating with methionine sulfoxide levels. An allosteric effect between Met54, Trp51, and residues involved in receptor binding is proposed. These results indicate that methionine oxidation has no effect on the folded structure and global thermodynamic stability of the recombinant human erythropoietin molecule. Oxidation can affect potency, but only at levels significantly in excess of those seen in EPREX.

  15. In the mood for love or vice versa? Exploring the relations among sexual activity, physical affection, affect, and stress in the daily lives of mid-aged women.

    PubMed

    Burleson, Mary H; Trevathan, Wenda R; Todd, Michael

    2007-06-01

    How do physical affection, sexual activity, mood, and stress influence one another in the daily lives of mid-aged women? Fifty-eight women (M age, 47.6 yrs) recorded physical affection, several different sexual behaviors, stressful events, and mood ratings every morning for 36 weeks. Using multilevel modeling, we determined that physical affection or sexual behavior with a partner on one day significantly predicted lower negative mood and stress and higher positive mood on the following day. The relation did not hold for orgasm without a partner. Additionally, positive mood on one day predicted more physical affection and sexual activity with a partner, but fewer solo orgasms the following day. Negative mood was mostly unrelated to next-day sexual activity or physical affection. Sexual orientation, living with a partner, and duration of relationship moderated some of these effects. Results support a bidirectional causal model in which dyadic sexual interaction and physical affection improve mood and reduce stress, with improved mood and reduced stress in turn increasing the likelihood of future sex and physical affection.

  16. The effect of galactose ingestion on affect and perceived exertion in recreationally active females.

    PubMed

    Duckworth, Lauren C; Backhouse, Susan H; Stevenson, Emma J

    2013-12-01

    The beneficial effects of acute carbohydrate (CHO) supplementation on exercise performance have been well described. Also reported is the attenuation of perceived exertion and enhancement of affect during prolonged exercise following CHO ingestion. However, no studies to date have assessed the impact of the type of CHO ingested on affective responses during moderate intensity exercise, lasting 60 min or less. Therefore, the aim of the present study was to investigate the effects of consuming a galactose (GAL) CHO drink versus a glucose (GLU) CHO or placebo (PLA) drink before and during exercise on affect and perceived exertion. Nine recreationally active females undertook three trials, each consisting of running for 60 min at 65% VO2max followed immediately by a 90 min rest period. Prior to (300 ml) and at every 15 min during exercise (150 ml), participants consumed either a GLU or GAL drink each containing 45 g of CHO, or an artificially-sweetened PLA drink. Ratings of pleasure-displeasure and perceived activation were measured throughout exercise and the rest period and measures of perceived exertion were measured during exercise. Plasma glucose and serum insulin were significantly greater throughout exercise and rest following the GLU trial compared with the GAL and PLA trials (P<0.05). Measures of perceived activation and pleasure-displeasure were not enhanced nor RPE reduced as a result of ingestion of a CHO solution. In conclusion, the GAL beverage elicited a more favourable metabolic profile in the exercising females but this did not translate into an enhanced affective profile. Indeed, CHO ingestion had no noticeable effect on the assessed psychological indices during 60 min of moderate-intensity exercise in females. It is suggested that the maintenance of a positive affective profile may be explained more by the level of hydration as opposed to fuel availability. Therefore, those seeking to use beverages containing CHO to enhance their exercise experience

  17. Ionizing radiation affects human MART-1 melanoma antigen processing and presentation by dendritic cells.

    PubMed

    Liao, Yu-Pei; Wang, Chun-Chieh; Butterfield, Lisa H; Economou, James S; Ribas, Antoni; Meng, Wilson S; Iwamoto, Keisuke S; McBride, William H

    2004-08-15

    Radiation is generally considered to be an immunosuppressive agent that acts by killing radiosensitive lymphocytes. In this study, we demonstrate the noncytotoxic effects of ionizing radiation on MHC class I Ag presentation by bone marrow-derived dendritic cells (DCs) that have divergent consequences depending upon whether peptides are endogenously processed and loaded onto MHC class I molecules or are added exogenously. The endogenous pathway was examined using C57BL/6 murine DCs transduced with adenovirus to express the human melanoma/melanocyte Ag recognized by T cells (AdVMART1). Prior irradiation abrogated the ability of AdVMART1-transduced DCs to induce MART-1-specific T cell responses following their injection into mice. The ability of these same DCs to generate protective immunity against B16 melanoma, which expresses murine MART-1, was also abro