Human activity discrimination for maritime application

NASA Astrophysics Data System (ADS)

Boettcher, Evelyn; Deaver, Dawne M.; Krapels, Keith

2008-04-01

The US Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) is investigating how motion affects the target acquisition model (NVThermIP) sensor performance estimates. This paper looks specifically at estimating sensor performance for the task of discriminating human activities on watercraft, and was sponsored by the Office of Naval Research (ONR). Traditionally, sensor models were calibrated using still images. While that approach is sufficient for static targets, video allows one to use motion cues to aid in discerning the type of human activity more quickly and accurately. This, in turn, will affect estimated sensor performance and these effects are measured in order to calibrate current target acquisition models for this task. The study employed an eleven alternative forced choice (11AFC) human perception experiment to measure the task difficulty of discriminating unique human activities on watercrafts. A mid-wave infrared camera was used to collect video at night. A description of the construction of this experiment is given, including: the data collection, image processing, perception testing and how contrast was defined for video. These results are applicable to evaluate sensor field performance for Anti-Terrorism and Force Protection (AT/FP) tasks for the U.S. Navy.

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.

Activation of the ALT pathway for telomere maintenance can affect other sequences in the human genome.

PubMed

Jeyapalan, Jennie N; Varley, Helen; Foxon, Jenny L; Pollock, Raphael E; Jeffreys, Alec J; Henson, Jeremy D; Reddel, Roger R; Royle, Nicola J

2005-07-01

Immortal human cells maintain telomere length by the expression of telomerase or through the alternative lengthening of telomeres (ALT). The ALT mechanism involves a recombination-like process that allows the rapid elongation of shortened telomeres. However, it is not known whether activation of the ALT pathway affects other sequences in the genome. To address this we have investigated, in ALT-expressing cell lines and tumours, the stability of tandem repeat sequences known to mutate via homologous recombination in the human germline. We have shown extraordinary somatic instability in the human minisatellite MS32 (D1S8) in ALT-expressing (ALT+) but not in normal or telomerase-expressing cell lines. The MS32 mutation frequency varied across 15 ALT+ cell lines and was on average 55-fold greater than in ALT- cell lines. The MS32 minisatellite was also highly unstable in three of eight ALT+ soft tissue sarcomas, indicating that somatic destabilization occurs in vivo. The MS32 mutation rates estimated for two ALT+ cell lines were similar to that seen in the germline. However, the internal structures of ALT and germline mutant alleles are very different, indicating differences in the underlying mutation mechanisms. Five other hypervariable minisatellites did not show elevated instability in ALT-expressing cell lines, indicating that minisatellite destabilization is not universal. The elevation of MS32 instability upon activation of the ALT pathway and telomere length maintenance suggests there is overlap between the underlying processes that may be tractable through analysis of the D1S8 locus.

The synthetic ligand of peroxisome proliferator-activated receptor-gamma ciglitazone affects human glioblastoma cell lines.

PubMed

Strakova, Nicol; Ehrmann, Jiri; Dzubak, Petr; Bouchal, Jan; Kolar, Zdenek

2004-06-01

Glioblastoma multiforme is the most common malignant brain tumor in adults, and it is among the most lethal of all cancers. Recent studies have shown that ligand activation of peroxisome proliferator-activated receptor (PPAR)-gamma can induce differentiation and inhibit proliferation of several cancer cells. In this study, we have investigated whether one PPARgamma ligand in particular, ciglitazone, inhibits cell viability and, additionally, whether it affects the cell cycle and apoptosis of human glioblastoma cell lines T98G, U-87 MG, A172, and U-118 MG. All glioblastoma cell lines were found to express PPARgamma protein, and following treatment with ciglitazone, localization was unchanged. Ciglitazone inhibited viability in a dose-dependent manner in all four tested glioblastoma cells after 24 h of treatment. Analysis of the cell cycle showed arrest in the G(1) phase and partial block in G(2)/M phase of the cell cycle. Cyclin D1 and cyclin B expression was decreased. Phosphorylation of Rb protein dropped as well. We found that ciglitazone was followed by increased expression of p27(Kip1) and p21(Waf1/Cip1). It also led to apoptosis induction: bax expression in T98G was elevated. Expression of the antiapoptotic protein bcl-2 was reduced in U-118 MG and U-87 MG and showed a slight decrease in A172 cells. Flow cytometry confirmed the induction of apoptosis. Moreover, PPARgamma ligand decreased telomerase activity in U-87 MG and U-118 MG cell lines. Our results demonstrate that ciglitazone inhibits the viability of human glioblastoma cell lines via induction of apoptosis; as a result, this ligand may offer potential new therapy for the treatment of central nervous system neoplasms.

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)

Cell culture density affects the proliferation activity of human adipose tissue stem cells.

PubMed

Kim, Dae Seong; Lee, Myoung Woo; Ko, Young Jong; Chun, Yong Hoon; Kim, Hyung Joon; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

2016-01-01

In this study, we investigated the effect of cell density on the proliferation activity of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT-MSCs) over time in culture. Passage #4 (P4) and #12 (P12) AT-MSCs from two donors were plated at a density of 200 (culture condition 1, CC1) or 5000 (culture condition 2, CC2) cells cm(-2) . After 7 days of incubation, P4 and P12 AT-MSCs cultured in CC1 were thin and spindle-shaped, whereas those cultured in CC2 had extensive cell-to-cell contacts and an expanded cell volume. In addition, P4 and P12 AT-MSCs in CC1 divided more than three times, while those in CC2 divided less than once on average. Flow cytometric analysis using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester dye showed that the fluorescence intensity of AT-MSCs was lower in CC1 than in CC2. Furthermore, expression of proliferation-associated genes, such as CDC45L, CDC20A and KIF20A, in P4 AT-MSCs was higher in CC1 than in CC2, and this difference was also observed in P12 AT-MSCs. These data demonstrated that cell culture density affects the proliferation activity of MSCs, suggesting that it is feasible to design a strategy to prepare suitable MSCs using specific culture conditions. Copyright © 2016 John Wiley & Sons, Ltd.

[Influence of human activities on groundwater environment based on coefficient variation method].

PubMed

Zhao, Wei; Lin, Jian; Wang, Shu-Fang; Liu, Ji-Lai; Chen, Zhong-Rong; Kou, Wen-Jie

2013-04-01

Groundwater system in the plain area of Beijing can be divided into six subsystems. Due to the different hydrogeological conditions of the subsystems, the degrees to which human activities affect the subsystems are also diverse. In order to evaluate the influence of human activities on each subsystem, the first and second aquifer with relatively poor water quality were chosen to be the evaluating positions, based on the data of groundwater sampled in September, 2011. With respect to human activities affect index such as total hardness, TDS, sulfate and ammonium, variation coefficient methods were used to calculate the weight of each index. Then scores were obtained for each index with national standard as reference, and superposition calculations were used to gain comprehensive scores, finally the groundwater quality conditions were evaluated. Contrast analyses were used to evaluate the incidence of human activities with groundwater subsystems as evaluation unit and water quality partitions as evaluation factors. The results indicate that the influence of human activities on the first aquifer is greater than that of the second aquifer, the Yongding river groundwater subsystems and the Chaobai river groundwater subsystems are affected more than other groundwater subsystems.

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.

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.

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

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.

Human NK Cell Subset Functions Are Differentially Affected by Adipokines

PubMed Central

Huebner, Lena; Engeli, Stefan; Wrann, Christiane D.; Goudeva, Lilia; Laue, Tobias; Kielstein, Heike

2013-01-01

Background Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods Isolated human peripheral blood mononuclear cells (PBMCs) were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS). Results FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), granzyme A (GzmA) and interferon (IFN)-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56dim NK cells. The production of GzmA in CD56bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R), TRAIL and IFN-γ were species-specific. Conclusion Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation. PMID:24098717

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

PubMed

Zeng, Huawei; Jackson, Matthew I; Cheng, Wen-Hsing; Combs, Gerald F

2011-11-01

Determining the effect of selenium (Se) chemical form on uptake, transport, and glutathione peroxidase activity in human intestinal cells is critical to assess Se bioavailability at nutritional doses. In this study, we found that two sources of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular Se content more effectively than selenite or methylselenocysteine (SeMSC) in the human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se-enriched yeast were transported at comparable efficacy from the apical to basolateral sides, each being about 3-fold that of selenite. In addition, these forms of Se, whether before or after traversing from apical side to basolateral side, did not change the potential to support glutathione peroxidase (GPx) activity. Although selenoprotein P has been postulated to be a key Se transport protein, its intracellular expression did not differ when selenite, SeMSC, SeMet, or digested Se-enriched yeast was added to serum-contained media. Taken together, our data show, for the first time, that the chemical form of Se at nutritional doses can affect the absorptive (apical to basolateral side) efficacy and retention of Se by intestinal cells; but that, these effects are not directly correlated to the potential to support GPx activity.

High temperature affects the phagocytic activity of human peripheral blood mononuclear cells.

PubMed

Djaldetti, Meir; Bessler, Hanna

2015-10-01

The ability for engulfment of pathogens and inert particles is the key hallmark of the phagocytic cells. Phagocytes play a significant role in the modulation of local or extended inflammation. Since fever activates a number of factors linked with the immune response it was the goal of this study to examine the in vitro effect of hyperthermia on the phagocytic capacity, the number of phagocytic cells and the viability of human peripheral blood mononuclear cells (PBMC) at 37 and 40°C. PBMC were incubated with 0.8 μm polysterene latex beads, for 2 hours at 37 and 40°C. The number of phagocytic cells, and that of latex particles internalized by each individual cell was counted with a light microscope. In addition, the percentage of viable cells and the number of active metabolic cells was evaluated. A temperature of 40°C significantly increased the number of phagocytic cells and the phagocytic index by 41 and 37% respectively, as compared to cells incubated at 37°C. While the number of vital cells (trypan blue test) did not differ statistically at both temperatures, the number of active metabolic cells (XTT test) after 2 h of incubation at 40°C was 17% higher as compared with that at 37°C. However, the number of active metabolic cells after 24 h of incubation at 40°C was 51% lower compared with cells incubated at 37°C. The increased phagocytic capacity of human peripheral blood monocytes at high temperature further enlightens the immunomodulatory effect of fever in the immune responses during inflammation.

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.

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 Central

Freires, Irlan de Almeida; Murata, Ramiro Mendonça; Furletti, Vivian Fernandes; Sartoratto, Adilson; de Alencar, Severino Matias; 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. PMID:24901768

Don't worry, be active: positive affect and habitual physical activity.

PubMed

Pasco, Julie A; Jacka, Felice N; Williams, Lana J; Brennan, Sharon L; Leslie, Eva; Berk, Michael

2011-12-01

The aim of ths study was to examine the association between habitual physical activity and positive and negative affect. This cross-sectional study included 276 women aged 20 +, from the Geelong Osteoporosis Study. Habitual physical activity and other lifestyle exposures were assessed by questionnaire, concurrent with anthropometric assessments. Physical activity was categorized as very active, moderately active or sedentary. Positive and negative affect scores were derived from the validated 20 item Positive and Negative Affect Schedule (PANAS) self-report and were categorized into tertiles. There was a pattern of lower positive affect scores for lower levels of physical activity. With very active as the reference category, the odds for having a positive affect score in the highest tertile were sequentially lower for those who were moderately active (OR = 0.53, 95%CI 0.28-1.01) and sedentary (OR = 0.28, 95%CI 0.10-0.75). Associations were sustained after adjusting for body mass index and polypharmacy (OR = 0.50, 95%CI 0.26-0.96 and OR = 0.25, 95%CI 0.09-0.72, respectively). These associations were not explained by age, negative affect score or other exposures. No association was detected between physical activity and negative affect scores. This study reports that higher positive affect scores, encompassing emotions such as interest, excitement, enthusiasm and alertness, are associated with higher levels of habitual physical activity. These observations warrant further investigations into possible mechanistic interplay between neurobiological and psychosocial factors that underpin this association.

Affect and Subsequent Physical Activity: An Ambulatory Assessment Study Examining the Affect-Activity Association in a Real-Life Context.

PubMed

Niermann, Christina Y N; Herrmann, Christian; von Haaren, Birte; van Kann, Dave; Woll, Alexander

2016-01-01

Traditionally, cognitive, motivational, and volitional determinants have been used to explain and predict health behaviors such as physical activity. Recently, the role of affect in influencing and regulating health behaviors received more attention. Affects as internal cues may automatically activate unconscious processes of behavior regulation. The aim of our study was to examine the association between affect and physical activity in daily life. In addition, we studied the influence of the habit of being physically active on this relationship. An ambulatory assessment study in 89 persons (33.7% male, 25 to 65 years, M = 45.2, SD = 8.1) was conducted. Affect was assessed in the afternoon on 5 weekdays using smartphones. Physical activity was measured continuously objectively using accelerometers and subjectively using smartphones in the evening. Habit strength was assessed at the beginning of the diary period. The outcomes were objectively and subjectively measured moderate-to-vigorous physical activity (MVPA) performed after work. Multilevel regression models were used to analyze the association between affect and after work MVPA. In addition, the cross-level interaction of habit strength and affect on after work MVPA was tested. Positive affect was positively related to objectively measured and self-reported after work MVPA: the greater the positive affect the more time persons subsequently spent on MVPA. An inverse relationship was found for negative affect: the greater the negative affect the less time persons spent on MVPA. The cross-level interaction effect was significant only for objectively measured MVPA. A strong habit seems to strengthen both the positive influence of positive affect and the negative influence of negative affect. The results of this study confirm previous results and indicate that affect plays an important role for the regulation of physical activity behavior in daily life. The results for positive affect were consistent. However, in

Emotion-affected decision making in human simulation.

PubMed

Zhao, Y; Kang, J; Wright, D K

2006-01-01

Human modelling is an interdisciplinary research field. The topic, emotion-affected decision making, was originally a cognitive psychology issue, but is now recognized as an important research direction for both computer science and biomedical modelling. The main aim of this paper is to attempt to bridge the gap between psychology and bioengineering in emotion-affected decision making. The work is based on Ortony's theory of emotions and bounded rationality theory, and attempts to connect the emotion process with decision making. A computational emotion model is proposed, and the initial framework of this model in virtual human simulation within the platform of Virtools is presented.

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.

[Effects of human engineering activities on permafrost active layer and its environment in northern Qinghai-Tibetan plateau].

PubMed

Guo, Zhenggang; Wu, Qingbo; Niu, Fujun

2006-11-01

With disturbed and undisturbed belts during the construction of Qinghai-Tibet highway as test objectives, this paper studied the effects of human engineering activities on the permafrost ecosystem in northern Qinghai-Tibetan plateau. The results showed that the thickness of permafrost active layer was smaller in disturbed than in undisturbed belt, and decreased with increasing altitude in undisturbed belt while no definite pattern was observed in disturbed belt. Different vegetation types had different effects on the thickness of permafrost active layer, being decreased in the order of steppe > shrub > meadow. In the two belts, altitude was the main factor affecting the vertical distribution of soil moisture, but vegetation type was also an important affecting factor if the altitude was similar. Due to the human engineering activities, soil temperature in summer was lower in disturbed than in undisturbed belt.

Evaluation of Human Reliability in Selected Activities in the Railway Industry

NASA Astrophysics Data System (ADS)

Sujová, Erika; Čierna, Helena; Molenda, Michał

2016-09-01

The article focuses on evaluation of human reliability in the human - machine system in the railway industry. Based on a survey of a train dispatcher and of selected activities, we have identified risk factors affecting the dispatcher`s work and the evaluated risk level of their influence on the reliability and safety of preformed activities. The research took place at the authors` work place between 2012-2013. A survey method was used. With its help, authors were able to identify selected work activities of train dispatcher's risk factors that affect his/her work and the evaluated seriousness of its influence on the reliability and safety of performed activities. Amongst the most important finding fall expressions of unclear and complicated internal regulations and work processes, a feeling of being overworked, fear for one's safety at small, insufficiently protected stations.

Default, Cognitive, and Affective Brain Networks in Human Tinnitus

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-1-0491 TITLE: Default, Cognitive, and Affective Brain Networks in Human Tinnitus PRINCIPAL INVESTIGATOR: Jennifer R...SUBTITLE 5a. CONTRACT NUMBER Default, Cognitive and Affective Brain Networks in Human Tinnitus 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Tinnitus is a major health problem among those currently and formerly in military

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.

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

Human recreation affects spatio-temporal habitat use patterns in red deer (Cervus elaphus)

PubMed Central

Coppes, Joy; Burghardt, Friedrich; Hagen, Robert; Suchant, Rudi; Braunisch, Veronika

2017-01-01

The rapid spread and diversification of outdoor recreation can impact on wildlife in various ways, often leading to the avoidance of disturbed habitats. To mitigate human-wildlife conflicts, spatial zonation schemes can be implemented to separate human activities from key wildlife habitats, e.g., by designating undisturbed wildlife refuges or areas with some level of restriction to human recreation and land use. However, mitigation practice rarely considers temporal differences in human-wildlife interactions. We used GPS telemetry data from 15 red deer to study the seasonal (winter vs. summer) and diurnal (day vs. night) variation in recreation effects on habitat use in a study region in south-western Germany where a spatial zonation scheme has been established. Our study aimed to determine if recreation infrastructure and spatial zonation affected red deer habitat use and whether these effects varied daily or seasonally. Recreation infrastructure did not affect home range selection in the study area, but strongly determined habitat use within the home range. The spatial zonation scheme was reflected in both of these two levels of habitat selection, with refuges and core areas being more frequently used than the border zones. Habitat use differed significantly between day and night in both seasons. Both summer and winter recreation trails, and nearby foraging habitats, were avoided during day, whereas a positive association was found during night. We conclude that human recreation has an effect on red deer habitat use, and when designing mitigation measures daily and seasonal variation in human-wildlife interactions should be taken into account. We advocate using spatial zonation in conjunction with temporal restrictions (i.e., banning nocturnal recreation activities) and the creation of suitable foraging habitats away from recreation trails. PMID:28467429

River Networks and Human Activities: Global Fractal Analysis Using Nightlight Data

NASA Astrophysics Data System (ADS)

McCurley, K. 4553; Fang, Y.; Ceola, S.; Paik, K.; McGrath, G. S.; Montanari, A.; Rao, P. S.; Jawitz, J. W.

2016-12-01

River networks hold an important historical role in affecting human population distribution. In this study, we link the geomorphological structure of river networks to the pattern of human activities at a global scale. We use nightlights as a valuable proxy for the presence of human settlements and economic activity, and we employ HydroSHEDS as the main data source on river networks. We test the hypotheses that, analogous to Horton's laws, human activities (magnitude of nightlights) also show scaling relationship with stream order, and that the intensity of human activities decrease as the distance from the basin outlet increase. Our results demonstrate that the distribution of human activities shows a fractal structure, with power-law scaling between human activities and stream order. This relationship is robust among global river basins. Human activities are more concentrated in larger order basins, but show large variation in equivalent order basins, with higher population density emergent in the basins connected with high-order rivers. For all global river basins longer than 400km, the average intensity of human activities decrease as the distance to the outlets increases, albeit with signatures of large cities at varied distances. The power spectrum of human width (area) function is found to exhibit power law scaling, with a scaling exponent that indicates enrichment of low frequency variation. The universal fractal structure of human activities may reflect an optimum arrangement for humans in river basins to better utilize the water resources, ecological assets, and geographic advantages. The generalized patterns of human activities could be applied to better understand hydrologic and biogeochemical responses in river basins, and to advance catchment management.

Defense Human Resources Activity > PERSEREC

Science.gov Websites

Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

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

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

Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi

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 humanmore » 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

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

Effects of human activity of breeding American Oystercatchers, Cumberland Island National Seashore, Georgia, USA

USGS Publications Warehouse

Sabine, J.B.; Meyers, J.M.; Moore, C.T.; Schweitzer, Sara H.

2008-01-01

Abstract.-Increased human use of coastal areas threatens the United States population of American Oystercatchers (Haematopus palliatus), a species of special concern. Biologists often attribute its low numbers and reproductive success to human disturbance, but the mechanism by which human presence reduces reproductive success is not well understood. During the 2003 and 2004 breeding seasons, 32 nesting attempts of American Oystercatchers were studied on Cumberland Island National Seashore (CINS). Behavior was examined with and without human activity in the area to determine how human activity affected behavior. The oystercatchers' behavioral responses (proportion time) were analyzed with and without human or intraspecific disturbances using mixed models regression analysis. Proportions of time human activities were present (137 m and vehicular activity should be minimized at current levels or less.

The influence of periodic increases of human activity on crepuscular and nocturnal mammals: Testing the weekend effect.

PubMed

Nix, Joshua H; Howell, Ryan G; Hall, Lucas K; McMillan, Brock R

2018-01-01

Human recreation can negatively affect wildlife, particularly on weekends when human activity is highest (i.e., the weekend effect). Much of what we understand about the weekend effect is based on research conducted on diurnal species, which have greater temporal overlap with humans. Because nocturnal species generally avoid times when humans are active, they are likely less affected by anthropogenic activity on weekends. Our objective was to test the weekend effect in relation to the degree of nocturnality of mammals in a recreational area. We predicted that as nocturnality increased, the effect of human activity would decrease. To address our objective, we placed 50 remote cameras along the Diamond Fork River in Utah from January to June 2015. We found that three out of the four focal species supported our predictions. Mule deer (crepuscular) reduced activity throughout our entire study area during weekends and avoided campgrounds. Beavers and mountain lions (both nocturnal) did not negatively respond to increased human activity. Raccoons (nocturnal) reduced activity during weekends, but only within campground areas. Our findings indicate that as the temporal overlap increases between wildlife and humans, so does the influence that humans have on wildlife. Copyright © 2017 Elsevier B.V. All rights reserved.

Affective processes in human-automation interactions.

PubMed

Merritt, Stephanie M

2011-08-01

This study contributes to the literature on automation reliance by illuminating the influences of user moods and emotions on reliance on automated systems. Past work has focused predominantly on cognitive and attitudinal variables, such as perceived machine reliability and trust. However, recent work on human decision making suggests that affective variables (i.e., moods and emotions) are also important. Drawing from the affect infusion model, significant effects of affect are hypothesized. Furthermore, a new affectively laden attitude termed liking is introduced. Participants watched video clips selected to induce positive or negative moods, then interacted with a fictitious automated system on an X-ray screening task At five time points, important variables were assessed including trust, liking, perceived machine accuracy, user self-perceived accuracy, and reliance.These variables, along with propensity to trust machines and state affect, were integrated in a structural equation model. Happiness significantly increased trust and liking for the system throughout the task. Liking was the only variable that significantly predicted reliance early in the task. Trust predicted reliance later in the task, whereas perceived machine accuracy and user self-perceived accuracy had no significant direct effects on reliance at any time. Affective influences on automation reliance are demonstrated, suggesting that this decision-making process may be less rational and more emotional than previously acknowledged. Liking for a new system may be key to appropriate reliance, particularly early in the task. Positive affect can be easily induced and may be a lever for increasing liking.

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.

HUMAN EXPOSURE ACTIVITY PATTERNS

EPA Science Inventory

Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

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.

Human calprotectin affects the redox speciation of iron.

PubMed

Nakashige, Toshiki G; Nolan, Elizabeth M

2017-08-16

We report that the metal-sequestering human host-defense protein calprotectin (CP, S100A8/S100A9 oligomer) affects the redox speciation of iron (Fe) in bacterial growth media and buffered aqueous solution. Under aerobic conditions and in the absence of an exogenous reducing agent, CP-Ser (S100A8(C42S)/S100A9(C3S) oligomer) depletes Fe from three different bacterial growth media preparations over a 48 h timeframe (T = 30 °C). The presence of the reducing agent β-mercaptoethanol accelerates this process and allows CP-Ser to deplete Fe over a ≈1 h timeframe. Fe-depletion assays performed with metal-binding-site variants of CP-Ser show that the hexahistidine (His 6 ) site, which coordinates Fe(ii) with high affinity, is required for Fe depletion. An analysis of Fe redox speciation in buffer containing Fe(iii) citrate performed under aerobic conditions demonstrates that CP-Ser causes a time-dependent increase in the [Fe(ii)]/[Fe(iii)] ratio. Taken together, these results indicate that the hexahistidine site of CP stabilizes Fe(ii) and thereby shifts the redox equilibrium of Fe to the reduced ferrous state under aerobic conditions. We also report that the presence of bacterial metabolites affects the Fe-depleting activity of CP-Ser. Supplementation of bacterial growth media with an Fe(iii)-scavenging siderophore (enterobactin, staphyloferrin B, or desferrioxamine B) attenuates the Fe-depleting activity of CP-Ser. This result indicates that formation of Fe(iii)-siderophore complexes blocks CP-mediated reduction of Fe(iii) and hence the ability of CP to coordinate Fe(ii). In contrast, the presence of pyocyanin (PYO), a redox-cycling phenazine produced by Pseudomonas aeruginosa that reduces Fe(iii) to Fe(ii), accelerates Fe depletion by CP-Ser under aerobic conditions. These findings indicate that the presence of microbial metabolites that contribute to metal homeostasis at the host/pathogen interface can affect the metal-sequestering function of CP.

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

Positive affect and physical activity: Testing effects on goal setting, activation, prioritisation, and attainment.

PubMed

Cameron, David S; Bertenshaw, Emma J; Sheeran, Paschal

2018-02-01

The present research tested whether incidental positive affect promotes pursuit of physical activity goals. Four key features of goal pursuit were examined - setting physical activity goals (Study 1), goal activation (Study 2), and goal prioritization and goal attainment (Study 3). Participants (N s = 80, 81, and 59, in Studies 1-3, respectively) were randomized to positive affect (joy, hope) or neutral affect (control) conditions in each study. Questionnaire measures of goal level, goal commitment, and means selection (Study 1); a lexical decision task indexed goal activation (Study 2), a choice task captured goal prioritization and MET minutes quantified goal attainment (Study 3). Study 1 showed that positive affect led to a greater number of intended physical activities, and that joy engendered greater willingness to try activities. In Study 2, a positive affect induction led to heightened activation of the physical activity goal compared to the control condition. The joy induction in Study 3 led to greater physical activity, and a trend towards greater goal prioritization. These findings suggest that positive affect enhances the pursuit of physical activity goals. Implications for health behavior theories and interventions are outlined.

Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells.

PubMed

Wang, C; Ye, Z; Kijlstra, A; Zhou, Y; Yang, P

2014-08-01

Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases. © 2014 British Society for Immunology.

Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells

PubMed Central

Wang, C; Ye, Z; Kijlstra, A; Zhou, Y; Yang, P

2014-01-01

Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases. PMID:24749687

Affective Biases in Humans and Animals.

PubMed

Robinson, E S J; Roiser, J P

Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies.

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

Momentary assessment of contextual influences on affective response during physical activity.

PubMed

Dunton, Genevieve Fridlund; Liao, Yue; Intille, Stephen; Huh, Jimi; Leventhal, Adam

2015-12-01

Higher positive and lower negative affective response during physical activity may reinforce motivation to engage in future activity. However, affective response during physical activity is typically examined under controlled laboratory conditions. This research used ecological momentary assessment (EMA) to examine social and physical contextual influences on momentary affective response during physical activity in naturalistic settings. Participants included 116 adults (mean age = 40.3 years, 73% female) who completed 8 randomly prompted EMA surveys per day for 4 days across 3 semiannual waves. EMA surveys measured current activity level, social context, and physical context. Participants also rated their current positive and negative affect. Multilevel models assessed whether momentary physical activity level moderated differences in affective response across contexts controlling for day of the week, time of day, and activity intensity (measured by accelerometer). The Activity Level × Alone interaction was significant for predicting positive affect (β = -0.302, SE = 0.133, p = .024). Greater positive affect during physical activity was reported when with other people (vs. alone). The Activity Level × Outdoors interaction was significant for predicting negative affect (β = -0.206, SE = 0.097, p = .034). Lower negative affect during physical activity was reported outdoors (vs. indoors). Being with other people may enhance positive affective response during physical activity, and being outdoors may dampen negative affective response during physical activity. (c) 2015 APA, all rights reserved).

Physical activity and negative affective reactivity in daily life.

PubMed

Puterman, Eli; Weiss, Jordan; Beauchamp, Mark R; Mogle, Jacqueline; Almeida, David M

2017-12-01

The results from experimental studies indicate that physically active individuals remain calmer and report less anxiety after the induction of a standardized stressor. The current study extends this research to real life, and examines whether daily physical activity attenuates negative affect that occurs in response to naturally occurring daily stressors. The current study used data from the second wave of the National Study of Daily Experiences, a sub-study of the second wave of the Midlife in the United States Study (MIDUS-II) of 2,022 individuals aged 33-84 questioned nightly for eight consecutive days about their general affect and affective responses to stressful events and their engagement in physical activity. Results indicated that while negative affect is significantly elevated on days with stressful events compared to days free of events in all individuals, these effects are attenuated in those who remain physically active when compared to those who were underactive. This was also true for any day participants were physically active. Importantly, negative affect in response to any specific stressor was reduced the closer in time that the stressor occurred to the bout of exercise in underactive participants, while, in active participants, negative affect in response to any stressor remained low throughout the entire day that participants reported that they were active. Given the significant mental and physical health implications of elevated affective reactivity observed in previous studies, the current study sheds further light on the importance of remaining physically active in times of stress. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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.

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

Cognitive-Affective Dimensions of Female Orgasm: The Role of Automatic Thoughts and Affect During Sexual Activity.

PubMed

Tavares, Inês M; Laan, Ellen T M; Nobre, Pedro J

2017-06-01

Cognitive-affective factors contribute to female sexual dysfunctions, defined as clinically significant difficulties in the ability to respond sexually or to experience sexual pleasure. Automatic thoughts and affect presented during sexual activity are acknowledged as maintenance factors for these difficulties. However, there is a lack of studies on the influence of these cognitive-affective dimensions regarding female orgasm. To assess the role of automatic thoughts and affect during sexual activity in predicting female orgasm occurrence and to investigate the mediator role of these variables in the relation between sexual activity and orgasm occurrence. Nine hundred twenty-six sexually active heterosexual premenopausal women reported on frequency of sexual activities and frequency of orgasm occurrence, cognitive factors, and social desirability. Participants completed the Sexual Modes Questionnaire-Automatic Thoughts Subscale, the Positive and Negative Affect Schedule, and the Socially Desirable Response Set. Multiple linear regressions and mediation analyses were performed, controlling for the effect of covariates such as social desirability, sociodemographic and medical characteristics, and relationship factors. The main outcome measurement was orgasm frequency as predicted and mediated by automatic thoughts and affect experienced during sexual activities. The presence of failure thoughts and lack of erotic thoughts during sexual activity significantly and negatively predicted female orgasm, whereas positive affect experienced during sexual activity significantly and positively predicted female orgasm. Moreover, negative automatic thoughts and positive affect during sexual activity were found to mediate the relation between sexual activity and female orgasm occurrence. These data suggest that the cognitive aspects of sexual involvement are critical to enhancing female orgasm experience and can aid the development of strategies that contemplate the central role

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.

Sperm DNA fragmentation affects epigenetic feature in human male pronucleus.

PubMed

Rajabi, H; Mohseni-Kouchesfehani, H; Eslami-Arshaghi, T; Salehi, M

2018-02-01

To evaluate whether the sperm DNA fragmentation affects male pronucleus epigenetic factors, semen analysis was performed and DNA fragmentation was assessed by the method of sperm chromatin structure assay (SCSA). Human-mouse interspecies fertilisation was used to create human male pronucleus. Male pronucleus DNA methylation and H4K12 acetylation were evaluated by immunostaining. Results showed a significant positive correlation between the level of sperm DNA fragmentation and DNA methylation in male pronuclei. In other words, an increase in DNA damage caused an upsurge in DNA methylation. In the case of H4K12 acetylation, no correlation was detected between DNA damage and the level of histone acetylation in the normal group, but results for the group in which male pronuclei were derived from sperm cells with DNA fragmentation, increased DNA damage led to a decreased acetylation level. Sperm DNA fragmentation interferes with the active demethylation process and disrupts the insertion of histones into the male chromatin in the male pronucleus, following fertilisation. © 2017 Blackwell Verlag GmbH.

Metformin selectively affects human glioblastoma tumor-initiating cell viability

PubMed Central

Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirana; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2013-01-01

Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect. PMID:23255107

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

Immunocapture and microplate-based activity and quantity measurement of pyruvate dehydrogenase in human peripheral blood mononuclear cells.

PubMed

Liu, Xiaowen; Pervez, Hira; Andersen, Lars W; Uber, Amy; Montissol, Sophia; Patel, Parth; Donnino, Michael W

2015-01-01

Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). RESULTS/METHODOLOGY: We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects. Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease.

Antioxidative Activity of Colostrum and Human Milk: Effects of Pasteurization and Storage.

PubMed

Marinković, Vesna; Ranković-Janevski, Milica; Spasić, Snežana; Nikolić-Kokić, Aleksandra; Lugonja, Nikoleta; Djurović, Dijana; Miletić, Srdjan; Vrvić, Miroslav M; Spasojević, Ivan

2016-06-01

Milk banks collect, pasteurize, and freeze/store human milk. The processing may alter redox properties of milk, but the effects have not been fully examined. We collected 10 mature milk and 10 colostrum samples and applied a battery of biochemical assays and electron paramagnetic resonance spectroscopy to inspect changes that milk undergoes with pasteurization and 30 days storage at -20°C. Pasteurization and storage of raw milk did not affect total nonenzymatic antioxidative capacity, but specific components and features were altered. Urate radical and ascorbyl radical emerge as products of exposure of milk to hydroxyl radical-generating system. Processing shifted the load of antioxidative activity from ascorbate to urate and lowered the capacity of milk to diminish hydroxyl radical. Pasteurization caused a significant drop in the activity of 2 major antioxidative enzymes-superoxide dismutase and glutathione peroxidase, whereas freezing/storage of raw milk affected only superoxide dismutase. Colostrum showed drastically higher total nonenzymatic antioxidative capacity, hydroxyl radical scavenging ability, and glutathione reductase activity compared with mature milk. Pasteurization and storage affect nonenzymatic and enzymatic antioxidative agents in human milk. It appears that nonenzymatic antioxidative systems in colostrum and milk are different. The effects of processing may be partially compensated by fortification/spiking with ascorbate before use.

Oocyte cryopreservation and in vitro culture affect calcium signalling during human fertilization.

PubMed

Nikiforaki, D; Vanden Meerschaut, F; Qian, C; De Croo, I; Lu, Y; Deroo, T; Van den Abbeel, E; Heindryckx, B; De Sutter, P

2014-01-01

What are the precise patterns of calcium oscillations during the fertilization of human oocytes matured either in vivo or in vitro or aged in vitro and what is the effect of cryopreservation? Human oocytes matured in vivo exhibit a specific pattern of calcium oscillations, which is affected by in vitro maturation, in vitro ageing and cryopreservation. Oscillations in cytoplasmic calcium concentration are crucial for oocyte activation and further embryonic development. While several studies have described in detail the calcium oscillation pattern during fertilization in animal models, studies with human oocytes are scarce. This was a laboratory-based study using human MII oocytes matured in vivo or in vitro either fresh or after cryopreservation with slow freezing or vitrification. Altogether, 205 human oocytes were included in the analysis. In vivo and in vitro matured human oocytes were used for this research either fresh or following vitrification/warming (V/W) and slow freezing/thawing (F/T). Human oocytes were obtained following written informed consent from patients undergoing ovarian hyperstimulation. For the calcium pattern analysis, oocytes were loaded with the ratiometric calcium indicator fluorescent dye Fura-2. Following ICSI using sperm from a single donor, intracellular calcium was measured for 16 h at 37°C under 6% CO(2). The calcium oscillation parameters were calculated for all intact oocytes that showed calcium oscillations and were analyzed using the Mann-Whitney U-test. Human in vivo MII oocytes display a specific pattern of calcium oscillations following ICSI. This pattern is significantly affected by in vitro ageing, with the calcium oscillations occurring over a longer period of time and with a lower frequency, shorter duration and higher amplitude (P < 0.05). In vitro matured oocytes from the GV and MI stage exhibit a different pattern of calcium oscillations with calcium transients being of lower frequency and shorter duration compared with

Immunocapture and microplate-based activity and quantity measurement of pyruvate dehydrogenase in human peripheral blood mononuclear cells

PubMed Central

Liu, Xiaowen; Pervez, Hira; Andersen, Lars W; Uber, Amy; Montissol, Sophia; Patel, Parth; Donnino, Michael W

2015-01-01

Background Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). Results/Methodology We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects. Conclusion Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease. PMID:25826140

Affect, exercise, and physical activity among healthy adolescents.

PubMed

Schneider, Margaret; Dunn, Andrea; Cooper, Daniel

2009-12-01

Many adolescents do not meet public health recommendations for moderate-to-vigorous physical activity (MVPA). In studies of variables influencing adolescent MVPA, one that has been understudied is the affective response to exercise. We hypothesized that adolescents with a more positive affective response to acute exercise would be more active. Adolescents (N = 124; 46% male) completed two 30-min exercise tasks (above and below the ventilatory threshold [VT]), and wore ActiGraph accelerometers for 6.5 +/- 0.7 days. Affective valence was assessed before, during, and after each task. A more positive affective response during exercise below the VT was associated with greater participation in MVPA (p < .05). The results are consistent with the hypothesis that individuals who have a more positive affective response to exercise will engage in more MVPA. To promote greater participation in MVPA among adolescents, programs should be designed to facilitate a positive affective experience during exercise.

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

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

Lynch, Caitlin; Pan, Yongmei; Li, Linhao

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 evaluatedmore » 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. �

High-throughput identification of small molecules that affect human embryonic vascular development

PubMed Central

Vazão, Helena; Rosa, Susana; Barata, Tânia; Costa, Ricardo; Pitrez, Patrícia R.; Honório, Inês; de Vries, Margreet R.; Papatsenko, Dimitri; Benedito, Rui; Saris, Daniel; Khademhosseini, Ali; Quax, Paul H. A.; Pereira, Carlos F.; Mercader, Nadia; Ferreira, Lino

2017-01-01

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions. These cells were then used to screen compounds that specifically affect embryonic vasculature. Using this platform, we have identified two compounds that have higher inhibitory effect in embryonic than postnatal ECs. One of them was fluphenazine (an antipsychotic), which inhibits calmodulin kinase II. The other compound was pyrrolopyrimidine (an antiinflammatory agent), which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), decreases EC viability, induces an inflammatory response, and disrupts preformed vascular networks. The vascular effect of the pyrrolopyrimidine was further validated in prenatal vs. adult mouse ECs and in embryonic and adult zebrafish. We developed a platform based on human pluripotent stem cell-derived ECs for drug screening, which may open new avenues of research for the study and modulation of embryonic vasculature. PMID:28348206

High-throughput identification of small molecules that affect human embryonic vascular development.

PubMed

Vazão, Helena; Rosa, Susana; Barata, Tânia; Costa, Ricardo; Pitrez, Patrícia R; Honório, Inês; de Vries, Margreet R; Papatsenko, Dimitri; Benedito, Rui; Saris, Daniel; Khademhosseini, Ali; Quax, Paul H A; Pereira, Carlos F; Mercader, Nadia; Fernandes, Hugo; Ferreira, Lino

2017-04-11

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions. These cells were then used to screen compounds that specifically affect embryonic vasculature. Using this platform, we have identified two compounds that have higher inhibitory effect in embryonic than postnatal ECs. One of them was fluphenazine (an antipsychotic), which inhibits calmodulin kinase II. The other compound was pyrrolopyrimidine (an antiinflammatory agent), which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), decreases EC viability, induces an inflammatory response, and disrupts preformed vascular networks. The vascular effect of the pyrrolopyrimidine was further validated in prenatal vs. adult mouse ECs and in embryonic and adult zebrafish. We developed a platform based on human pluripotent stem cell-derived ECs for drug screening, which may open new avenues of research for the study and modulation of embryonic vasculature.

Human T lymphocytes express N-methyl-D-aspartate receptors functionally active in controlling T cell activation

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

Miglio, Gianluca; Varsaldi, Federica; Lombardi, Grazia

2005-12-30

The aim of this study was to investigate the expression and the functional role of N-methyl-D-aspartate (NMDA) receptors in human T cells. RT-PCR analysis showed that human resting peripheral blood lymphocytes (PBL) and Jurkat T cells express genes encoding for both NR1 and NR2B subunits: phytohemagglutinin (PHA)-activated PBL also expresses both these genes and the NR2A and NR2D genes. Cytofluorimetric analysis showed that NR1 expression increases as a consequence of PHA (10 {mu}g/ml) treatment. D-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)-MK 801], competitive and non-competitive NMDA receptor antagonists, respectively, inhibited PHA-induced T cell proliferation, whereas they did not affect IL-2 (10more » U/ml)-induced proliferation of PHA blasts. These effects were due to the prevention of T cell activation (inhibition of cell aggregate formation and CD25 expression), but not to cell cycle arrest or death. These results demonstrate that human T lymphocytes express NMDA receptors, which are functionally active in controlling cell activation.« less

Hydrolysis of platelet-activating factor by human serum paraoxonase.

PubMed Central

Rodrigo, L; Mackness, B; Durrington, P N; Hernandez, A; Mackness, M I

2001-01-01

Human serum paraoxonase (human PON1) has been shown to be important in the metabolism of phospholipid and cholesteryl ester hydroperoxides, thereby preventing the oxidation of low-density lipoprotein (LDL) and retarding atherogenesis. However, the exact substrate specificity of PON1 has not been established. In the present study we show that purified PON1 hydrolyses platelet-activating factor (PAF). We could find no evidence for contamination of our preparation with authentic platelet-activating-factor acetylhydrolase (PAFAH) by immunoblotting with a PAFAH monoclonal antibody or by sequencing the purified protein. In addition the specific PAFAH inhibitor SB-222657 did not affect the ability of PON1 to hydrolyse PAF (30.1+/-2.8 micromol/min per mg of protein with no inhibitor; 31.4+/-2.2 micromol/min per mg of protein with 100 nM inhibitor) or phenyl acetate (242.6+/-30.8 versus 240.8+/-31.5 micromol/min per mg of protein with and without inhibitor respectively). SB-222657 was also unable to inhibit PAF hydrolysis by isolated human high-density lipoprotein (HDL), but completely abolished the activity of human LDL. Ostrich (Struthio camelus) HDL, which does not contain PON1, was unable to hydrolyse PAF. These data provide evidence that PON1 may limit the action of this bioactive pro-inflammatory phospholipid. PMID:11171072

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

Contributions of climate change and human activities to runoff change in seven typical catchments across China.

PubMed

Zhai, Ran; Tao, Fulu

2017-12-15

Climate change and human activities are two major factors affecting water resource change. It is important to understand the roles of the major factors in affecting runoff change in different basins for watershed management. Here, we investigated the trends in climate and runoff in seven typical catchments in seven basins across China from 1961 to 2014. Then we attributed the runoff change to climate change and human activities in each catchment and in three time periods (1980s, 1990s and 2000s), using the VIC model and long-term runoff observation data. During 1961-2014, temperature increased significantly, while the trends in precipitation were insignificant in most of the catchments and inconsistent among the catchments. The runoff in most of the catchments showed a decreasing trend except the Yingluoxia catchment in the northwestern China. The contributions of climate change and human activities to runoff change varied in different catchments and time periods. In the 1980s, climate change contributed more to runoff change than human activities, which was 84%, 59%, -66%, -50%, 59%, 94%, and -59% in the Nianzishan, Yingluoxia, Xiahui, Yangjiaping, Sanjiangkou, Xixian, and Changle catchment, respectively. After that, human activities had played a more essential role in runoff change. In the 1990s and 2000s, human activities contributed more to runoff change than in the 1980s. The contribution by human activities accounted for 84%, -68%, and 67% in the Yingluoxia, Xiahui, and Sanjiangkou catchment, respectively, in the 1990s; and -96%, -67%, -94%, and -142% in the Nianzishan, Yangjiaping, Xixian, and Changle catchment, respectively, in the 2000s. It is also noted that after 2000 human activities caused decrease in runoff in all catchments except the Yingluoxia. Our findings highlight that the effects of human activities, such as increase in water withdrawal, land use/cover change, operation of dams and reservoirs, should be well managed. Copyright © 2017 Elsevier

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…

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.

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

Corrugator activity confirms immediate negative affect in surprise.

PubMed

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.

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

[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.

The Midwest Stream Quality Assessment—Influences of human activities on streams

USGS Publications Warehouse

Van Metre, Peter C.; Mahler, Barbara J.; Carlisle, Daren M.; Coles, James F.

2018-04-16

Healthy streams and the fish and other organisms that live in them contribute to our quality of life. Extensive modification of the landscape in the Midwestern United States, however, has profoundly affected the condition of streams. Row crops and pavement have replaced grasslands and woodlands, streams have been straightened, and wetlands and fields have been drained. Runoff from agricultural and urban land brings sediment and chemicals to streams. What is the chemical, physical, and biological condition of Midwestern streams? Which physical and chemical stressors are adversely affecting biological communities, what are their origins, and how might we lessen or avoid their adverse effects?In 2013, the U.S. Geological Survey (USGS) conducted the Midwest Stream Quality Assessment to evaluate how human activities affect the biological condition of Midwestern streams. In collaboration with the U.S. Environmental Protection Agency National Rivers and Streams Assessment, the USGS sampled 100 streams, chosen to be representative of the different types of watersheds in the region. Biological condition was evaluated based on the number and diversity of fish, algae, and invertebrates in the streams. Changes to the physical habitat and chemical characteristics of the streams—“stressors”—were assessed, and their relation to landscape factors and biological condition was explored by using mathematical models. The data and models help us to better understand how the human activities on the landscape are affecting streams in the region.

Strategies for protecting Western Burrowing Owls (Speotyto cunicularia hypugaea) from human activities

Treesearch

Lynne A. Trulio

1997-01-01

Practitioners have been using numerous methods to protect Burrowing Owls (Speotyto cunicularia hypugaea) affected by human activities. Primary approaches include protecting birds and burrows in place, allowing birds to relocate within their nesting territory, allowing birds to colonize new patches, moving birds within the geographic region and moving...

Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.

PubMed

Herklotz, Manuela; Hanke, Jasmin; Hänsel, Stefanie; Drichel, Juliane; Marx, Monique; Maitz, Manfred F; Werner, Carsten

2016-10-01

Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Cow's milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors alpha and delta and retinoid X receptor alpha involved in the regulation of energy homeostasis, obesity, and inflammation.

PubMed

Suhara, W; Koide, H; Okuzawa, T; Hayashi, D; Hashimoto, T; Kojo, H

2009-09-01

The nuclear peroxisome proliferator-activated receptors (PPAR) have been shown to play crucial roles in regulating energy homeostasis including lipid and carbohydrate metabolism, inflammatory responses, and cell proliferation, differentiation, and survival. Because PPAR agonists have the potential to prevent or ameliorate diseases such as hyperlipidemia, diabetes, atherosclerosis, and obesity, we have explored new natural agonists for PPAR. For this purpose, cow's milk was tested for agonistic activity toward human PPAR subtypes using a reporter gene assay. Milk increased human PPARalpha activity in a dose-dependent manner with a 3.2-fold increase at 0.5% (vol/vol). It also enhanced human PPARdelta activity in a dose-dependent manner with an 11.5-fold increase at 0.5%. However, it only slightly affected human PPARgamma activity. Ice cream, butter, and yogurt also increased the activities of PPARalpha and PPARdelta, whereas vegetable cream affected activity of PPARdelta but not PPARalpha. Skim milk enhanced the activity of PPAR to a lesser degree than regular milk. Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta. Both milk and fresh cream were shown by quantitative real-time PCR to increase the quantity of mRNA for uncoupling protein 2 (UCP2), an energy expenditure gene, in a dose-dependent manner. The increase in UCP2 mRNA was found to be reduced by treatment with PPARdelta-short interfering (si)RNA. This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha. The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.

Incorporating twitter-based human activity information in spatial analysis of crashes in urban areas.

PubMed

Bao, Jie; Liu, Pan; Yu, Hao; Xu, Chengcheng

2017-09-01

The primary objective of this study was to investigate how to incorporate human activity information in spatial analysis of crashes in urban areas using Twitter check-in data. This study used the data collected from the City of Los Angeles in the United States to illustrate the procedure. The following five types of data were collected: crash data, human activity data, traditional traffic exposure variables, road network attributes and social-demographic data. A web crawler by Python was developed to collect the venue type information from the Twitter check-in data automatically. The human activities were classified into seven categories by the obtained venue types. The collected data were aggregated into 896 Traffic Analysis Zones (TAZ). Geographically weighted regression (GWR) models were developed to establish a relationship between the crash counts reported in a TAZ and various contributing factors. Comparative analyses were conducted to compare the performance of GWR models which considered traditional traffic exposure variables only, Twitter-based human activity variables only, and both traditional traffic exposure and Twitter-based human activity variables. The model specification results suggested that human activity variables significantly affected the crash counts in a TAZ. The results of comparative analyses suggested that the models which considered both traditional traffic exposure and human activity variables had the best goodness-of-fit in terms of the highest R 2 and lowest AICc values. The finding seems to confirm the benefits of incorporating human activity information in spatial analysis of crashes using Twitter check-in data. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

Impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased.

PubMed

Chen, Ming; Qin, Xiaosheng; Zeng, Guangming; Li, Jian

2016-06-01

Groundwater quality deterioration has attracted world-wide concerns due to its importance for human water supply. Although more and more studies have shown that human activities and climate are changing the groundwater status, an investigation on how different groundwater heavy metals respond to human activity modes (e.g. mining, waste disposal, agriculture, sewage effluent and complex activity) in a varying climate has been lacking. Here, for each of six heavy metals (i.e. Fe, Zn, Mn, Pb, Cd and Cu) in groundwater, we use >330 data points together with mixed-effect models to indicate that (i) human activity modes significantly influence the Cu and Mn but not Zn, Fe, Pb and Cd levels, and (ii) annual mean temperature (AMT) only significantly influences Cu and Pb levels, while annual precipitation (AP) only significantly affects Fe, Cu and Mn levels. Given these differences, we suggest that the impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased. Copyright © 2016 Elsevier Ltd. All rights reserved.

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... in or affecting commerce. Section 7A(a)(1) is satisfied if any entity included within the acquiring person, or any entity included within the acquired person, is engaged in commerce or in any activity...

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... in or affecting commerce. Section 7A(a)(1) is satisfied if any entity included within the acquiring person, or any entity included within the acquired person, is engaged in commerce or in any activity...

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... in or affecting commerce. Section 7A(a)(1) is satisfied if any entity included within the acquiring person, or any entity included within the acquired person, is engaged in commerce or in any activity...

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... in or affecting commerce. Section 7A(a)(1) is satisfied if any entity included within the acquiring person, or any entity included within the acquired person, is engaged in commerce or in any activity...

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... in or affecting commerce. Section 7A(a)(1) is satisfied if any entity included within the acquiring person, or any entity included within the acquired person, is engaged in commerce or in any activity...

The regulation of catalase activity by PPAR γ is affected by α-synuclein

PubMed Central

Yakunin, Eugenia; Kisos, Haya; Kulik, Willem; Grigoletto, Jessica; Wanders, Ronald J A; Sharon, Ronit

2014-01-01

Objective While evidence for oxidative injury is frequently detected in brains of humans affected by Parkinson's disease (PD) and in relevant animal models, there is uncertainty regarding its cause. We tested the potential role of catalase in the oxidative injury that characterizes PD. Methods Utilizing brains of A53T α-Syn and ntg mice, and cultured cells, we analyzed catalase activity and expression, and performed biochemical analyses of peroxisomal metabolites. Results Lower catalase expression and lower activity levels were detected in A53T α-Syn brains and α-Syn-expressing cells. The effect on catalase activity was independent of disease progression, represented by mouse age and α-Syn mutation, suggesting a potential physiological function for α-Syn. Notably, catalase activity and expression were unaffected in brains of mice modeling Alzheimer's disease. Moreover, we found that α-Syn expression downregulate the peroxisome proliferator-activated receptor (PPAR)γ, which controls catalase transcription. Importantly, activation of either PPARγ2, PPARα or retinoic X receptor eliminated the inhibiting effect of α-Syn on catalase activity. In addition, activation of these nuclear receptors enhanced the accumulation of soluble α-Syn oligomers, resulting in a positive association between the degree of soluble α-Syn oligomers and catalase activity. Of note, a comprehensive biochemical analysis of specific peroxisomal metabolites indicated no signs of dysfunction in specific peroxisomal activities in brains of A53T α-Syn mice. Interpretation Our results suggest that α-Syn expression may interfere with the complex and overlapping network of nuclear receptors transcription activation. In result, catalase activity is affected through mechanisms involved in the regulation of soluble α-Syn oligomers. PMID:25356396

Automatic response activation in sequential affective priming: an ERP study

PubMed Central

Leuthold, Hartmut; Rothermund, Klaus; Schweinberger, Stefan R.

2012-01-01

Affective priming effects denote faster responses when two successively presented affective stimuli match in valence than when they mismatch. Two mechanisms have been proposed for their explanation: (i) Priming of affective information within a semantic network or distributed memory system (semantic priming). (ii) Automatic activation of the evaluative response through the affective prime (response priming). In this experiment, we sought more direct evidence for prime-induced response activations with measurement of the lateralized readiness potential (LRP). Onset of the stimulus-locked LRP was earlier in affectively congruent trials than in incongruent trials. In addition, priming modulated the LRP-amplitude of slow responses, indicating greater activation of the incorrect response hand in affectively incongruent trials. Onset of the response-locked LRP and peak latency of the P300 component were not modulated by priming but the amplitude of the N400 component was. In combination, these results suggest that both, semantic priming and response priming constitute affective priming effects in the evaluative categorization task. PMID:21642351

Constraints imposed by transmembrane domains affect enzymatic activity of membrane-associated human CD39/NTPDase1 mutants.

PubMed

Musi, Elgilda; Islam, Naziba; Drosopoulos, Joan H F

2007-05-01

Human CD39/NTPDase1 is an endothelial cell membrane-associated nucleotidase. Its large extracellular domain rapidly metabolizes nucleotides, especially ADP released from activated platelets, inhibiting further platelet activation/recruitment. Previous studies using our recombinant soluble CD39 demonstrated the importance of residues S57, D54, and D213 for enzymatic/biological activity. We now report effects of S57A, D54A, and D213A mutations on full-length (FL)CD39 function. Enzymatic activity of alanine modified FLCD39s was less than wild-type, contrasting the enhanced activity of their soluble counterparts. Furthermore, conservative substitutions D54E and D213E led to enzymes with activities greater than the alanine modified FLCD39s, but less than wild-type. Reductions in mutant activities were primarily associated with reduced catalytic rates. Differences in enzymatic activity were not attributable to gross changes in the nucleotide binding pocket or the enzyme's ability to multimerize. Thus, composition of the active site of wild-type CD39 appears optimized for ADPase function in the context of the transmembrane domains.

Intravital multiphoton tomography as a novel tool for non-invasive in vivo analysis of human skin affected with atopic dermatitis

NASA Astrophysics Data System (ADS)

Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Niemeyer, Verena; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.

2010-02-01

Atopic Dermatitis (AD) is an inflammatory disease of human skin. Its pathogenesis is still unknown; however, dysfunctions of the epidermal barrier and the immune response are regarded as key factors for the development of AD. In our study we applied intravital multiphoton tomography (5D-IVT), equipped with a spectral-FLIM module for in-vivo and ex-vivo analysis of human skin affected with AD. In addition to the morphologic skin analysis, FLIM technology gain access to the metabolic status of the epidermal cells referring to the NADH specific fluorescence lifetime. We evaluated a characteristic 5D-IVT skin pattern of AD in comparison to histological sections and detected a correlation with the disease activity measured by SCORAD. FLIM analysis revealed a shift of the mean fluorescence lifetime (taum) of NADH, indicating an altered metabolic activity. Within an ex-vivo approach we have investigated cryo-sections of human skin with or without barrier defects. Spectral-FLIM allows the detection of autofluorescent signals that reflect the pathophysiological conditions of the defect skin barrier. In our study the taum value was shown to be different between healthy and affected skin. Application of the 5D-IVT allows non-invasive in-vivo imaging of human skin with a penetration depth of 150 μm. We could show that affected skin could be distinguished from healthy skin by morphological criteria, by FLIM and by spectral-FLIM. Further studies will evaluate the application of the 5D-IVT technology as a diagnostic tool and to monitor the therapeutic efficacy.

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.

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.

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.

Antibacterial activity of recombinant human lactoferrin from rice: effect of heat treatment.

PubMed

Conesa, Celia; Rota, Carmen; Castillo, Eduardo; Pérez, María-Dolores; Calvo, Miguel; Sánchez, Lourdes

2009-06-01

The antibacterial activity of recombinant human lactoferrin from rice (rhLF) compared with that of human milk lactoferrin (hLF) was evaluated against Escherichia coli O157:H7, Salmonella Enteritidis and Listeria monocytogenes. The hydrolysates of rhLF and hLF were found to be more active than native proteins against E. coli O157:H7, and their activity was independent of their iron saturation. The effect of different heat treatments on the antibacterial activity of apo-rhLF was studied and compared with hLF. We observed that an HTST pasteurization treatment did not affect the antimicrobial activity of lactoferrin against the pathogens studied. Furthermore, the activity of apo-rhLF and hLF against E. coli O157:H7 and L. monocytogenes in UHT milk and whey was assayed, finding a decrease in the number of bacteria, although lower than that observed in a broth medium. This study shows the similar antibacterial activity of rhLF and hLF which is important in order to consider the addition of rhLF as a supplement in special products.

Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells

PubMed Central

Porter, Michael; Karp, Matthew; Killedar, Smruti; Bauer, Stephen M.; Guo, Jia; Williams, D'Ann; Breysse, Patrick; Georas, Steve N.; Williams, Marc A.

2007-01-01

Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-γ (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-γ production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material. PMID:17630318

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reduced Aβ secretion by human neurons under conditions of strongly increased BACE activity.

PubMed

Scholz, Diana; Chernyshova, Yana; Ückert, Anna-Katharina; Leist, Marcel

2018-05-27

The initial step in the amyloidogenic cascade of amyloid precursor protein (APP) processing is catalyzed by beta-site APP-cleaving enzyme (BACE), and this protease has increased activities in affected areas of Alzheimer's disease brains. We hypothesized that altered APP processing, due to augmented BACE activity, would affect the actions of direct and indirect BACE inhibitors. We therefore compared postmitotic human neurons (LUHMES) with their BACE-overexpressing counterparts (BLUHMES). Although β-cleavage of APP was strongly increased in BLUHMES, they produced less full-length and truncated amyloid beta (Aβ) than LUHMES. Moreover, low concentrations of BACE inhibitors decreased cellular BACE activity as expected, but increased Aβ 1-40 levels. Several other approaches to modulate BACE activity led to a similar, apparently paradoxical, behavior. For instance, reduction of intracellular acidification by bepridil increased Aβ production in parallel with decreased BACE activity. In contrast to BLUHMES, the respective control cells (LUHMES or BLUHMES with catalytically inactive BACE) showed conventional pharmacological responses. Other non-canonical neurochemical responses (so-called 'rebound effects') are well-documented for the Aβ pathway, especially for γ-secretase: a partial block of its activity leads to an increased Aβ secretion by some cell types. We therefore compared LUHMES and BLUHMES regarding rebound effects of γ-secretase inhibitors and found an Aβ rise in LUHMES but not in BLUHMES. Thus, different cellular factors are responsible for the γ-secretase- vs. BACE-related Aβ rebound. We conclude that increased BACE activity, possibly accompanied by an altered cellular localization pattern, can dramatically influence Aβ generation in human neurons and affect pharmacological responses to secretase inhibitors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells

PubMed Central

Zavašnik-Bergant, Tina; Bergant Marušič, Martina

2016-01-01

Dendritic cells (DC) play a pivotal role as antigen presenting cells (APC) and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70) during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii. PMID:26960148

The human milk oligosaccharides are not affected by pasteurization and freeze-drying.

PubMed

Hahn, Won-Ho; Kim, Jaehan; Song, Seunghyun; Park, Suyeon; Kang, Nam Mi

2017-11-06

Human milk oligosaccharides (HMOs) are known as important factors in neurologic and immunologic development of neonates. Moreover, freeze-drying seems to be a promising storage method to improve the processes of human milk banks. However, the effects of pasteurization and freeze-drying on HMOs were not evaluated yet. The purpose of this study is to analyze and compare the HMOs profiles of human milk collected before and after the pasteurization and freeze-drying. Totally nine fresh human milk samples were collected from three healthy mothers at the first, second, and third week after delivery. The samples were treated with Holder pasteurization and freeze-drying. HMOs profiles were analyzed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) mass spectrometry and compared between samples collected before and after the treatments. Human milk samples showed significantly different HMO patterns between mothers. However, HMOs were not affected by lactation periods within 3 weeks after delivery (r 2  = 0.972-0.999, p < .001). Moreover, both of pasteurization and freeze-drying were found not to affect HMO patterns in a correlation analysis (r 2  = 0.989-0.999, p < .001). HMO patterns were found not to be affected by pasteurization and freeze-drying of donor milks. We hope that introducing freeze-drying to the human milk banks would be encouraged by the present study. However, the storage length without composition changes of HMOs after freeze-drying needs to be evaluated in the further studies.

Activation of the Constitutive Androstane Receptor Inhibits Gluconeogenesis without Affecting Lipogenesis or Fatty Acid Synthesis in Human Hepatocytes

PubMed Central

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

2014-01-01

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. PMID:24878338

The rs662 polymorphism of paraoxonase 1 affects the difference in the inhibition of butyrylcholinesterase activity by organophosphorus pesticides in human blood.

PubMed

Nam, Dae Cheol; Ha, Yu Mi; Park, Min Kyu; Cho, Sung Kweon

2016-08-01

Organophosphorus pesticides (OPs) are a human health hazard. OPs inhibit acetylcholinesterase (AChE) at nerve endings and accumulate acetylcholine (ACh) at these sites. High levels of ACh and long exposure promote cholinergic crisis. The hydrolysis of OPs by serum paraoxonase 1 (PON1) plays a role in cholinergic crisis in humans. Human serum PON1 can break down organophosphate before binding to ChE. We investigated the effect of PON1 polymorphisms on AChE activity after OP treatment. 50 healthy volunteers were randomly recruited with informed consent. We investigated butyrylcholinesterase (BuChE) activity changes in plasma as a biomarker of AChE after OP treatment in human blood samples immediately following blood sampling. After the standardization of BuChE activity in human blood, we correlated changes in BuChE activity with changes in blood pH. We analyzed the PON1 polymorphisms (rs854560 and rs662) of 50 participants to retrospectively investigate the interindividual variability of changes in BuChE activity. Changes in BuChE activity are strongly correlated with pH changes after OP treatment (R2 = 0.913). We used changes in pH as a surrogate marker for BuChE inhibition after OP treatment. OP treatment significantly decreased BuChE activity by 56.4 ± 5.1% (p < 0.001). The degree of BuChE inhibition was significantly different in the PON1 rs662 genotype (56.10 ± 4.74% vs. 57.96 ± 5.67% vs. 52.34 ± 1.51%; GG vs. GA vs. AA, respectively). Changes in pH can be used as a surrogate marker for the detection of BuChE inhibition after OP exposure. The rs662 polymorphism of PON1 may explain the inter-individual variability in BuChE inhibition.

Anticipated affective consequences of physical activity adoption and maintenance.

PubMed

Dunton, Genevieve Fridlund; Vaughan, Elaine

2008-11-01

The expected emotional consequences of future actions are thought to play an important role in health behavior change. This research examined whether anticipated affective consequences of success and failure vary across stages of physical activity change and differentially predict physical activity adoption as compared to maintenance. Using a prospective design over a 3-month period, a community sample of 329 healthy, middle-aged adults were assessed at 2 time points. Anticipated positive and negative emotions, stage of behavior change (precontemplation [PC], contemplation [C], preparation [P], action [A], maintenance [M]), and level of physical activity. At baseline, anticipated positive emotions were greater in C versus PC, whereas anticipated negative emotions were greater in M versus A and in M versus P. Higher anticipated positive but not negative emotions predicted physical activity adoption and maintenance after 3 months. Although the expected affective consequences of future success and failure differentiated among individuals in the early and later stages of physical activity change, respectively; only the anticipated affective consequences of success predicted future behavior.

Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa.

PubMed

Zou, Qian-Xing; Peng, Zhen; Zhao, Qing; Chen, Hou-Yang; Cheng, Yi-Min; Liu, Qing; He, Yuan-Qiao; Weng, Shi-Qi; Wang, Hua-Feng; Wang, Tao; Zheng, Li-Ping; Luo, Tao

2017-02-01

Is diethylstilbestrol (DES), a prototypical endocrine-disrupting chemical (EDC), able to induce physiological changes in human spermatozoa and affect progesterone actions? DES promoted Ca 2+ flux into human spermatozoa by activating the cation channel of sperm (CatSper) and suppressed progesterone-induced Ca 2+ signaling, tyrosine phosphorylation and sperm functions. DES significantly impairs the male reproductive system both in fetal and postnatal exposure. Although various EDCs affect human spermatozoa in a non-genomic manner, the effect of DES on human spermatozoa remains unknown. Sperm samples from normozoospermic donors were exposed in vitro to a range of DES concentrations with or without progesterone at 37°C in a 5% CO 2 incubator to mimic the putative exposure to this toxicant in seminal plasma and the female reproductive tract fluids. The incubation time varied according to the experimental protocols. All experiments were repeated at least five times using different individual sperm samples. Human sperm intracellular calcium concentrations ([Ca 2+ ] i ) were monitored with a multimode plate reader following sperm loading with Ca 2+ indicator Fluo-4 AM, and the whole-cell patch-clamp technique was performed to record CatSper and alkalinization-activated sperm K + channel (KSper) currents. Sperm viability and motility parameters were assessed by an eosin-nigrosin staining kit and a computer-assisted semen analysis system, respectively. The ability of sperm to penetrate into viscous media was examined by penetration into 1% methylcellulose. The sperm acrosome reaction was measured using chlortetracycline staining. The level of tyrosine phosphorylation was determined by western blot assay. DES exposure rapidly increased human sperm [Ca 2+ ] i dose dependently and even at an environmentally relevant concentration (100 pM). The elevation of [Ca 2+ ] i was derived from extracellular Ca 2+ influx and mainly mediated by CatSper. Although DES did not affect sperm

Affective mediators of a physical activity intervention for depression in multiple sclerosis.

PubMed

Kratz, Anna L; Ehde, Dawn M; Bombardier, Charles H

2014-02-01

Previous analyses showed that a telephone-based intervention to increase physical activity in individuals with multiple sclerosis (MS) and depression resulted in significantly improved depressive symptoms compared to a wait-list control group. The aim of this study was to test positive affect and negative affect as mediators of the effect of the physical activity counseling on depressive symptoms. Ninety-two adults with MS, who met diagnostic criteria for either major depression or dysthymia and who reported low levels of physical activity, were randomized 1:1 to a 12-week telephone-based motivational interviewing (MI) intervention to improve physical activity (n = 44) or to a 12-week wait-list control group (n = 48). Self-reported positive and negative affect, physical activity, and depressive symptoms were gathered at baseline and postintervention. Path-analysis was used to test whether positive affect and negative affect mediated the positive effects of the intervention on depressive symptoms. Both positive and negative affect were significant mediators of the effects of the intervention on depressive symptoms; however, only positive affect mediated the association between changes in physical activity and improved depressive symptoms. Findings support physical activity and positive affect as key mediators of the MI treatment effect on improved mood. Decreases in negative affect were also evident in the treatment group, but were not related to improved physical activity. Findings may suggest the use of exercise-based interventions in conjunction with treatments that specifically target negative affective mechanisms for depression. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Brain Activity and Human Unilateral Chewing

PubMed Central

Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

2012-01-01

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

Culture temperature affects redifferentiation and cartilaginous extracellular matrix formation in dedifferentiated human chondrocytes.

PubMed

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

2015-05-01

To date, there have been few studies on how temperature affects the phenotype and metabolism of human chondrocytes. Thus, the purpose of this study was to elucidate the effects of culture temperature on chondrocyte redifferentiation and extracellular matrix (ECM) formation using dedifferentiated mature human chondrocytes in vitro. Dedifferentiated chondrocytes were cultured in a pellet culture system for up to 21 days. The pellets were randomly divided into three groups with different culture temperature (32, 37, and 41°C). Chondrocyte redifferentiation and ECM formation were evaluated by wet weight, messenger ribonucleic acid (mRNA), histological, and biochemical analyses. The results showed that the wet weight and the mRNA expressions of collagen type II A1 and cartilage oligomeric matrix protein at 37°C were higher than the corresponding values at 32°C. The histological and biochemical analyses revealed that the syntheses of type II collagen and proteoglycan were promoted at 37°C compared to those at 32°C, whereas they were considerably inhibited at 41°C. In conclusion, the results obtained herein indicated that temperature affects chondrocyte redifferentiation and ECM formation, and modulation of temperature might thus represent an advantageous means to regulate the phenotype and biosynthetic activity of chondrocytes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Benzydamine N-oxidation as an index reaction reflecting FMO activity in human liver microsomes and impact of FMO3 polymorphisms on enzyme activity

PubMed Central

Störmer, Elke; Roots, Ivar; Brockmöller, Jürgen

2000-01-01

Aims The role of flavin containing monooxygenases (FMO) on the disposition of many drugs has been insufficiently explored. In vitro and in vivo tests are required to study FMO activity in humans. Benzydamine (BZD) N-oxidation was evaluated as an index reaction for FMO as was the impact of genetic polymorphisms of FMO3 on activity. Methods BZD was incubated with human liver microsomes (HLM) and recombinant enzymes. Human liver samples were genotyped using PCR-RFLP. Results BZD N-oxide formation rates in HLM followed Michaelis-Menten kinetics (mean Km = 64.0 μm, mean Vmax = 6.9 nmol mg−1 protein min−1; n = 35). N-benzylimidazole, a nonspecific CYP inhibitor, and various CYP isoform selective inhibitors did not affect BZD N-oxidation. In contrast, formation of BZD N-oxide was almost abolished by heat treatment of microsomes in the absence of NADPH and strongly inhibited by methimazole, a competitive FMO inhibitor. Recombinant FMO3 and FMO1 (which is not expressed in human liver), but not FMO5, showed BZD N-oxidase activity. Respective Km values for FMO3 and FMO1 were 40.4 μm and 23.6 μm, and respective Vmax values for FMO3 and FMO1 were 29.1 and 40.8 nmol mg−1 protein min−1. Human liver samples (n = 35) were analysed for six known FMO3 polymorphisms. The variants I66M, P135L and E305X were not detected. Samples homozygous for the K158 variant showed significantly reduced vmax values (median 2.7 nmol mg−1 protein min−1) compared to the carriers of at least one wild type allele (median 6.2 nmol mg−1 protein min−1) (P<0.05, Mann–Whitney- U-test). The V257M and E308G substitutions had no effect on enzyme activity. Conclusions BZD N-oxidation in human liver is mainly catalysed by FMO3 and enzyme activity is affected by FMO3 genotype. BZD may be used as a model substrate for human liver FMO3 activity in vitro and may be further developed as an in vivo probe reflecting FMO3 activity. PMID:11136294

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

Associations of Affective Responses During Free-Living Physical Activity and Future Physical Activity Levels: an Ecological Momentary Assessment Study.

PubMed

Liao, Yue; Chou, Chih-Ping; Huh, Jimi; Leventhal, Adam; Dunton, Genevieve

2017-08-01

Affective response during physical activity may influence motivation to perform future physical activity behavior. However, affective response during physical activity is often assessed under controlled laboratory conditions. The current study used ecological momentary assessment (EMA) to capture affective responses during free-living physical activity performed by adults, and determined whether these affective responses predict future moderate-to-vigorous physical activity (MVPA) levels after 6 and 12 months. At baseline, electronic EMA surveys were randomly prompted across 4 days asking about current activities and affective states (e.g., happy, stressed, energetic, tired). Affective response during physical activity was operationalized as the level of positive or negative affect reported when concurrent physical activity (e.g., exercise or sports) was also reported. Data were available for 82 adults. Future levels of moderate-to-vigorous physical activity (MVPA) were measured using accelerometers, worn for seven consecutive days at 6 and 12 months after the baseline assessment. Feeling more energetic during physical activity was associated with performing more minutes of daily MVPA after both 6 and 12 months. Feeling less negative affect during physical activity was associated with engaging in more daily MVPA minutes after 12 months only. This study demonstrated how EMA can be used to capture affective responses during free-living physical activity. Results found that feelings more energetic and less negative during physical activity were associated with more future physical activity, suggesting that positive emotional benefits may reinforce behavior.

Affective responses in tamarins elicited by species-specific music

PubMed Central

Snowdon, Charles T.; Teie, David

2010-01-01

Theories of music evolution agree that human music has an affective influence on listeners. Tests of non-humans provided little evidence of preferences for human music. However, prosodic features of speech (‘motherese’) influence affective behaviour of non-verbal infants as well as domestic animals, suggesting that features of music can influence the behaviour of non-human species. We incorporated acoustical characteristics of tamarin affiliation vocalizations and tamarin threat vocalizations into corresponding pieces of music. We compared music composed for tamarins with that composed for humans. Tamarins were generally indifferent to playbacks of human music, but responded with increased arousal to tamarin threat vocalization based music, and with decreased activity and increased calm behaviour to tamarin affective vocalization based music. Affective components in human music may have evolutionary origins in the structure of calls of non-human animals. In addition, animal signals may have evolved to manage the behaviour of listeners by influencing their affective state. PMID:19726444

Vibration parameters affecting vibration-induced reflex muscle activity.

PubMed

Cidem, Muharrem; Karacan, Ilhan; Cakar, Halil Ibrahim; Cidem, Mehmet; Sebik, Oguz; Yilmaz, Gizem; Turker, Kemal Sitki; Karamehmetoglu, Safak Sahir

2017-03-01

To determine vibration parameters affecting the amplitude of the reflex activity of soleus muscle during low-amplitude whole-body vibration (WBV). This study was conducted on 19 participants. Vibration frequencies of 25, 30, 35, 40, 45, and 50 Hz were used. Surface electromyography, collision force between vibration platform and participant's heel measured using a force sensor, and acceleration measured using an accelerometer fixed to the vibration platform were simultaneously recorded. The collision force was the main independent predictor of electromyographic amplitude. The essential parameter of vibration affecting the amplitude of the reflex muscle activity is the collision force.

Salient sounds activate human visual cortex automatically.

PubMed

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

2013-05-22

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, this 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 2-4). 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 colocalized 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.

Segmentation and Recognition of Continuous Human Activity

DTIC Science & Technology

2001-01-01

This paper presents a methodology for automatic segmentation and recognition of continuous human activity . We segment a continuous human activity into...commencement or termination. We use single action sequences for the training data set. The test sequences, on the other hand, are continuous sequences of human ... activity that consist of three or more actions in succession. The system has been tested on continuous activity sequences containing actions such as

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

Cross-species affective neuroscience decoding of the primal affective experiences of humans and related animals.

PubMed

Panksepp, Jaak

2011-01-01

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. 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 brain regions. Such findings suggest

Affect-Aware Adaptive Tutoring Based on Human-Automation Etiquette Strategies.

PubMed

Yang, Euijung; Dorneich, Michael C

2018-06-01

We investigated adapting the interaction style of intelligent tutoring system (ITS) feedback based on human-automation etiquette strategies. Most ITSs adapt the content difficulty level, adapt the feedback timing, or provide extra content when they detect cognitive or affective decrements. Our previous work demonstrated that changing the interaction style via different feedback etiquette strategies has differential effects on students' motivation, confidence, satisfaction, and performance. The best etiquette strategy was also determined by user frustration. Based on these findings, a rule set was developed that systemically selected the proper etiquette strategy to address one of four learning factors (motivation, confidence, satisfaction, and performance) under two different levels of user frustration. We explored whether etiquette strategy selection based on this rule set (systematic) or random changes in etiquette strategy for a given level of frustration affected the four learning factors. Participants solved mathematics problems under different frustration conditions with feedback that adapted dynamic changes in etiquette strategies either systematically or randomly. The results demonstrated that feedback with etiquette strategies chosen systematically via the rule set could selectively target and improve motivation, confidence, satisfaction, and performance more than changing etiquette strategies randomly. The systematic adaptation was effective no matter the level of frustration for the participant. If computer tutors can vary the interaction style to effectively mitigate negative emotions, then ITS designers would have one more mechanism in which to design affect-aware adaptations that provide the proper responses in situations where human emotions affect the ability to learn.

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides

PubMed Central

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-01-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. PMID:26747427

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

PubMed

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-05-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. © The Author 2016. Published by Oxford University Press.

Perceived somatic and affective barriers for self-efficacy and physical activity.

PubMed

Warner, Lisa M; Wolff, Julia K; Spuling, Svenja M; Wurm, Susanne

2017-05-01

According to Bandura's social-cognitive theory, perceptions of somatic and affective barriers are sources of self-efficacy. This longitudinal study compares general indicators of health barriers with measures of perceived somatic and affective barriers to predict self-efficacy and accelerometer-assessed physical activity in a subsample of n = 153 (selected at random from N = 310) community-dwelling German older adults. Perceived somatic and affective barriers longitudinally predicted physical activity mediated by self-efficacy, whereas general health barriers did not. Perceived health barriers to physical activity might be more important than more objective health barriers for older adults' physical activity levels.

Activation of mouse and human Peroxisome Proliferator-Activated Receptor-alpha (PPARa) by Perfluoroalkyl Acids(PFAAs): Further investigation of C4-C12 compounds.

EPA Science Inventory

Perfluorinated alkyl acids (PFAAs) are manufactured surfactants found globally in the environment and in tissues of humans and wildlife. Several PFAAs adversely affect rodents and activation of PPARa is thought to be their mode of action. Our previous study demonstrated that some...

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

A human intermediate conductance calcium-activated potassium channel.

PubMed

Ishii, T M; Silvia, C; Hirschberg, B; Bond, C T; Adelman, J P; Maylie, J

1997-10-14

An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is approximately 50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 microM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3. 5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 microM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel.

Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine*

PubMed Central

Shields-Cutler, Robin R.; Crowley, Jan R.; Miller, Connelly D.; Stapleton, Ann E.; Cui, Weidong; Henderson, Jeffrey P.

2016-01-01

In human urinary tract infections, host cells release the antimicrobial protein siderocalin (SCN; also known as lipocalin-2, neutrophil gelatinase-associated lipocalin, or 24p3) into the urinary tract. By binding to ferric catechol complexes, SCN can sequester iron, a growth-limiting nutrient for most bacterial pathogens. Recent evidence links the antibacterial activity of SCN in human urine to iron sequestration and metabolomic variation between individuals. To determine whether these metabolomic associations correspond to functional Fe(III)-binding SCN ligands, we devised a biophysical protein binding screen to identify SCN ligands through direct analysis of human urine. This screen revealed a series of physiologic unconjugated urinary catechols that were able to function as SCN ligands of which pyrogallol in particular was positively associated with high urinary SCN activity. In a purified, defined culture system, these physiologic SCN ligands were sufficient to activate SCN antibacterial activity against Escherichia coli. In the presence of multiple SCN ligands, native mass spectrometry demonstrated that SCN may preferentially combine different ligands to coordinate iron, suggesting that availability of specific ligand combinations affects in vivo SCN antibacterial activity. These results support a mechanistic link between the human urinary metabolome and innate immune function. PMID:27780864

The Affective Impact of Financial Skewness on Neural Activity and Choice

PubMed Central

Wu, Charlene C.; Bossaerts, Peter; Knutson, Brian

2011-01-01

Few finance theories consider the influence of “skewness” (or large and asymmetric but unlikely outcomes) on financial choice. We investigated the impact of skewed gambles on subjects' neural activity, self-reported affective responses, and subsequent preferences using functional magnetic resonance imaging (FMRI). Neurally, skewed gambles elicited more anterior insula activation than symmetric gambles equated for expected value and variance, and positively skewed gambles also specifically elicited more nucleus accumbens (NAcc) activation than negatively skewed gambles. Affectively, positively skewed gambles elicited more positive arousal and negatively skewed gambles elicited more negative arousal than symmetric gambles equated for expected value and variance. Subjects also preferred positively skewed gambles more, but negatively skewed gambles less than symmetric gambles of equal expected value. Individual differences in both NAcc activity and positive arousal predicted preferences for positively skewed gambles. These findings support an anticipatory affect account in which statistical properties of gambles—including skewness—can influence neural activity, affective responses, and ultimately, choice. PMID:21347239

Activation of ERK mitogen-activated protein kinase in human cells by the mycotoxin patulin

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

Wu, T.-S.; Yu, F.-Y.; Su, C.-C.

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}Mmore » 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.« less

ADHESIVES WITH DIFFERENT PHS: EFFECT ON THE MTBS OF CHEMICALLY ACTIVATED AND LIGHT-ACTIVATED COMPOSITES TO HUMAN DENTIN

PubMed Central

Mallmann, André; de Melo, Renata Marques; Estrela, Verbênia; Pelogia, Fernanda; Campos, Laura; Bottino, Marco Antonio; Valandro, Luiz Felipe

2007-01-01

Purpose: To evaluate the bond strength between human dentin and composites, using two light-activated single-bottle total-etch adhesive systems with different pHs combined with chemically activated and light-activated-composites. The tested hypothesis was that the dentin bond strength is not influenced by an adhesive system of low pH, combined with chemically activated or light-activated composites. Material and Method: Flat dentin surfaces of twenty-eight human third molars were allocated in 4 groups (n=7), depending on the adhesive system: (One Step Plus-OS and Prime & Bond NT-PB) and composite (light-activated Filtek Z-100 [Z100] and chemically activated Bisfil 2B [B2B]). Each adhesive system was applied on acid-etched dentin and then one of the composites was added to form a 5 mm-high resin block. The specimens were stored in tap water (37°C/24 h) and sectioned into two axes, x and y. This was done with a diamond disk under coolant irrigation to obtain beams with a cross-section area of approximately 0.8 mm2. Each specimen was then attached to a custom-made device and submitted to the microtensile test (1 mm.min−1). Data were analyzed using two-way ANOVA and Tukey’s tests (p<0.05). Results: The anticipated hypothesis was not confirmed (p<0.0001). The bond strengths (MPa) were not statistically different between the two adhesive systems when light-activated composite was used (OS+Z100 = 24.7±7.1ª; PB+Z100 = 23.8±5.7ª). However, with use of the chemically activated composite (B2B), PB (7.8±3.6b MPa) showed significantly lower dentin bond strengths than OS (32.2±7.6ª). Conclusion: The low pH of the adhesive system can affect the bond of chemically activated composite to dentin. On the other hand, under the present conditions, the low pH did not seem to affect the bond of light-activated composites to dentin significantly. PMID:19089142

An evolutionary perspective on human physical activity: implications for health.

PubMed

Eaton, S Boyd; Eaton, Stanley B

2003-09-01

At present, human genes and human lives are incongruent, especially in affluent Western nations. When our current genome was originally selected, daily physical exertion was obligatory; our biochemistry and physiology are designed to function optimally in such circumstances. However, today's mechanized, technologically oriented conditions allow and even promote an unprecedentedly sedentary lifestyle. Many important health problems are affected by this imbalance, including atherosclerosis, obesity, age-related fractures and diabetes, among others. Most physicians recognize that regular exercise is a critical component of effective health promotion regimens, but there is substantial disagreement about details, most importantly volume: how much daily caloric expenditure, as physical activity, is desirable. Because epidemiology-based recommendations vary, often confusing and alienating the health-conscious public, an independent estimate, arising from a separate scientific discipline, is desirable, at least for purposes of triangulation. The retrojected level of ancestral physical activity might meet this need. The best available such reconstruction suggests that the World Health Organization's recommendation, a physical activity level of 1.75 ( approximately 2.1 MJ (490 kcal)/d), most closely approximates the Paleolithic standard, that for which our genetic makeup was originally selected.

How Gamification Affects Physical Activity: Large-scale Analysis of Walking Challenges in a Mobile Application

PubMed Central

Shameli, Ali; Althoff, Tim; Saberi, Amin; Leskovec, Jure

2017-01-01

Gamification represents an effective way to incentivize user behavior across a number of computing applications. However, despite the fact that physical activity is essential for a healthy lifestyle, surprisingly little is known about how gamification and in particular competitions shape human physical activity. Here we study how competitions affect physical activity. We focus on walking challenges in a mobile activity tracking application where multiple users compete over who takes the most steps over a predefined number of days. We synthesize our findings in a series of game and app design implications. In particular, we analyze nearly 2,500 physical activity competitions over a period of one year capturing more than 800,000 person days of activity tracking. We observe that during walking competitions, the average user increases physical activity by 23%. Furthermore, there are large increases in activity for both men and women across all ages, and weight status, and even for users that were previously fairly inactive. We also find that the composition of participants greatly affects the dynamics of the game. In particular, if highly unequal participants get matched to each other, then competition suffers and the overall effect on the physical activity drops significantly. Furthermore, competitions with an equal mix of both men and women are more effective in increasing the level of activities. We leverage these insights to develop a statistical model to predict whether or not a competition will be particularly engaging with significant accuracy. Our models can serve as a guideline to help design more engaging competitions that lead to most beneficial behavioral changes. PMID:28990011

How Gamification Affects Physical Activity: Large-scale Analysis of Walking Challenges in a Mobile Application.

PubMed

Shameli, Ali; Althoff, Tim; Saberi, Amin; Leskovec, Jure

2017-04-01

Gamification represents an effective way to incentivize user behavior across a number of computing applications. However, despite the fact that physical activity is essential for a healthy lifestyle, surprisingly little is known about how gamification and in particular competitions shape human physical activity. Here we study how competitions affect physical activity. We focus on walking challenges in a mobile activity tracking application where multiple users compete over who takes the most steps over a predefined number of days. We synthesize our findings in a series of game and app design implications. In particular, we analyze nearly 2,500 physical activity competitions over a period of one year capturing more than 800,000 person days of activity tracking. We observe that during walking competitions, the average user increases physical activity by 23%. Furthermore, there are large increases in activity for both men and women across all ages, and weight status, and even for users that were previously fairly inactive. We also find that the composition of participants greatly affects the dynamics of the game. In particular, if highly unequal participants get matched to each other, then competition suffers and the overall effect on the physical activity drops significantly. Furthermore, competitions with an equal mix of both men and women are more effective in increasing the level of activities. We leverage these insights to develop a statistical model to predict whether or not a competition will be particularly engaging with significant accuracy. Our models can serve as a guideline to help design more engaging competitions that lead to most beneficial behavioral changes.

Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology

PubMed Central

Liu, Li-Li; Xian, Hua; Cao, Jing-Chen; Zhang, Chong; Zhang, Yong-Hui; Chen, Miao-Miao; Qian, Yi; Jiang, Ming

2015-01-01

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARγ acts as an important molecule for regulating energy homeostasis, modulates the hypothalamic-pituitary-gonadal (HPG) axis, and is reciprocally regulated by HPG. In the human, PPARγ protein is highly expressed in ejaculated spermatozoa, implying a possible role of PPARγ signaling in regulating sperm energy dissipation. PPARγ protein is also expressed in Sertoli cells and germ cells (spermatocytes). Its activation can be induced during capacitation and the acrosome reaction. This mini-review will focus on how PPARγ signaling may affect fertility and sperm quality and the potential reversibility of these adverse effects. PMID:25851655

The human ARF tumor suppressor senses blastema activity and suppresses epimorphic tissue regeneration

PubMed Central

Hesse, Robert G; Kouklis, Gayle K; Ahituv, Nadav; Pomerantz, Jason H

2015-01-01

The control of proliferation and differentiation by tumor suppressor genes suggests that evolution of divergent tumor suppressor repertoires could influence species’ regenerative capacity. To directly test that premise, we humanized the zebrafish p53 pathway by introducing regulatory and coding sequences of the human tumor suppressor ARF into the zebrafish genome. ARF was dormant during development, in uninjured adult fins, and during wound healing, but was highly expressed in the blastema during epimorphic fin regeneration after amputation. Regenerative, but not developmental signals resulted in binding of zebrafish E2f to the human ARF promoter and activated conserved ARF-dependent Tp53 functions. The context-dependent activation of ARF did not affect growth and development but inhibited regeneration, an unexpected distinct tumor suppressor response to regenerative versus developmental environments. The antagonistic pleiotropic characteristics of ARF as both tumor and regeneration suppressor imply that inducing epimorphic regeneration clinically would require modulation of ARF –p53 axis activation. DOI: http://dx.doi.org/10.7554/eLife.07702.001 PMID:26575287

Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors.

PubMed

Paul, Katie B; Thompson, Jerry T; Simmons, Steven O; Vanden Heuvel, John P; Crofton, Kevin M

2013-10-01

The bacteriostat triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) (TCS) decreases rat serum thyroxine via putative nuclear receptor (NR) interaction(s) and subsequent transcriptional up-regulation of hepatic catabolism and clearance. However, due to the evolutionary divergence of the constitutive androstane and pregnane-X receptors (CAR, PXR), TCS-mediated downstream effects may be species-dependent. To test the hypothesis that TCS activates xenobiotic NRs across species, cell-based NR reporter assays were employed to assess potential activation of rat, mouse, and human PXR, and rat, mouse, and three splice variants of human CAR. TCS activated hPXR, acted as an inverse agonist of hCAR1, and as a weak agonist of hCAR3. TCS failed to activate rPXR in full-length receptor reporter assays, and instead acted as a modest inverse agonist of rCAR. Consistent with the rat data, TCS also failed to activate mPXR and was a modest inverse agonist of mCAR. These data suggest that TCS may interact with multiple NRs, including hPXR, hCAR1, hCAR3, and rCAR in order to potentially affect hepatic catabolism. Overall these data support the conclusion that TCS may interact with NRs to regulate hepatic catabolism and downstream thyroid hormone homeostasis in both rat and human models, though perhaps by divergent mechanisms. Published by Elsevier Ltd.

The impact of human activities and lifestyles on the interlinked microbiota and health of humans and of ecosystems.

PubMed

Flandroy, Lucette; Poutahidis, Theofilos; Berg, Gabriele; Clarke, Gerard; Dao, Maria-Carlota; Decaestecker, Ellen; Furman, Eeva; Haahtela, Tari; Massart, Sébastien; Plovier, Hubert; Sanz, Yolanda; Rook, Graham

2018-06-15

Plants, animals and humans, are colonized by microorganisms (microbiota) and transiently exposed to countless others. The microbiota affects the development and function of essentially all organ systems, and contributes to adaptation and evolution, while protecting against pathogenic microorganisms and toxins. Genetics and lifestyle factors, including diet, antibiotics and other drugs, and exposure to the natural environment, affect the composition of the microbiota, which influences host health through modulation of interrelated physiological systems. These include immune system development and regulation, metabolic and endocrine pathways, brain function and epigenetic modification of the genome. Importantly, parental microbiotas have transgenerational impacts on the health of progeny. Humans, animals and plants share similar relationships with microbes. Research paradigms from humans and other mammals, amphibians, insects, planktonic crustaceans and plants demonstrate the influence of environmental microbial ecosystems on the microbiota and health of organisms, and indicate links between environmental and internal microbial diversity and good health. Therefore, overlapping compositions, and interconnected roles of microbes in human, animal and plant health should be considered within the broader context of terrestrial and aquatic microbial ecosystems that are challenged by the human lifestyle and by agricultural and industrial activities. Here, we propose research priorities and organizational, educational and administrative measures that will help to identify safe microbe-associated health-promoting modalities and practices. In the spirit of an expanding version of "One health" that includes environmental health and its relation to human cultures and habits (EcoHealth), we urge that the lifestyle-microbiota-human health nexus be taken into account in societal decision making. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Integrated Extravehicular Activity Human Research Plan: 2017

NASA Technical Reports Server (NTRS)

Abercromby, Andrew

2017-01-01

Multiple organizations within NASA as well as industry and academia fund and participate in research related to extravehicular activity (EVA). In October 2015, representatives of the EVA Office, the Crew and Thermal Systems Division (CTSD), and the Human Research Program (HRP) at NASA Johnson Space Center agreed on a formal framework to improve multi-year coordination and collaboration in EVA research. At the core of the framework is an Integrated EVA Human Research Plan and a process by which it will be annually reviewed and updated. The over-arching objective of the collaborative framework is to conduct multi-disciplinary cost-effective research that will enable humans to perform EVAs safely, effectively, comfortably, and efficiently, as needed to enable and enhance human space exploration missions. Research activities must be defined, prioritized, planned and executed to comprehensively address the right questions, avoid duplication, leverage other complementary activities where possible, and ultimately provide actionable evidence-based results in time to inform subsequent tests, developments and/or research activities. Representation of all appropriate stakeholders in the definition, prioritization, planning and execution of research activities is essential to accomplishing the over-arching objective. A formal review of the Integrated EVA Human Research Plan will be conducted annually. Coordination with stakeholders outside of the EVA Office, CTSD, and HRP is already in effect on a study-by-study basis; closer coordination on multi-year planning with other EVA stakeholders including academia is being actively pursued. Details of the preliminary Integrated EVA Human Research Plan are presented including description of ongoing and planned research activities in the areas of: physiological and performance capabilities; suit design parameters; EVA human health and performance modeling; EVA tasks and concepts of operations; EVA informatics; human-suit sensors; suit

Temporal dynamics of physical activity and affect in depressed and nondepressed individuals.

PubMed

Stavrakakis, Nikolaos; Booij, Sanne H; Roest, Annelieke M; de Jonge, Peter; Oldehinkel, Albertine J; Bos, Elisabeth H

2015-12-01

The association between physical activity and affect found in longitudinal observational studies is generally small to moderate. It is unknown how this association generalizes to individuals. The aim of the present study was to investigate interindividual differences in the bidirectional dynamic relationship between physical activity and affect, in depressed and nondepressed individuals, using time-series analysis. A pair-matched sample of 10 depressed and 10 nondepressed participants (mean age = 36.6, SD = 8.9, 30% males) wore accelerometers and completed electronic questionnaires 3 times a day for 30 days. Physical activity was operationalized as the total energy expenditure (EE) per day segment (i.e., 6 hr). The multivariate time series (T = 90) of every individual were analyzed using vector autoregressive modeling (VAR), with the aim to assess direct as well as lagged (i.e., over 1 day) effects of EE on positive and negative affect, and vice versa. Large interindividual differences in the strength, direction and temporal aspects of the relationship between physical activity and positive and negative affect were observed. An exception was the direct (but not the lagged) effect of physical activity on positive affect, which was positive in nearly all individuals. This study showed that the association between physical activity and affect varied considerably across individuals. Thus, while at the group level the effect of physical activity on affect may be small, in some individuals the effect may be clinically relevant. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Discovery of potent peptide-mimetic antagonists for the human thrombin receptor, protease-activated receptor-1 (PAR-1).

PubMed

Maryanoff, Bruce E; Zhang, Han-Cheng; Andrade-Gordon, Patricia; Derian, Claudia K

2003-03-01

Protease-activated receptors (PARs) represent a unique family of seven-transmembrane G-protein-coupled receptors, which are enzymatically cleaved to expose a new extracellular N-terminus that acts as a tethered activating ligand. PAR-1 is cleaved and activated by the serine protease alpha-thrombin, is expressed in various tissues (e.g. platelets and vascular cells), and is involved in cellular responses associated with hemostasis, proliferation, and tissue injury. By using a de novo design approach, we have discovered a series of potent heterocycle-based peptide-miimetic antagonists of PAR-1, exemplified by advanced leads RWJ-56110 (22) and RWJ-58259 (32). These compounds are potent, selective PAR-1 antagonists, devoid of PAR-1 agonist and thrombin inhibitory activity: they bind to PAR-1, interfere with calcium mobilization and cellular functions associated with PAR-1, and do not affect PAR-2, PAR-3, or PAR-4. RWJ-56110 was determined to be a direct inhibitor of PAR-1 activation and internalization, without affecting PAR-1 N-terminal cleavage. At high concentrations of alpha-thrombin, RWJ-56110 fully blocked activation responses in human vascular cells, but not in human platelets; whereas, at high concentrations of TRAP-6, RWJ-56110 blocked activation responses in both cell types. This result is consistent with the presence of another thrombin receptor on human platelets, namely PAR-4. RWJ-56110 and RWJ-58259 clearly interrupt the binding of a tethered ligand to its receptor. RWJ-58259 demonstrated antirestenotic activity in a rat balloon angioplasty model and antithrombotic activity in a cynomolgus monkey arterial injury model. Such PAR-1 antagonists should not only serve as useful tools to delineate the physiological and pathophysiological roles of PAR-1, but also may have therapeutic potential for treating thrombosis and restenosis in humans.

[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

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Latent Variables Affecting Behavioral Response to the Human Intruder Test in Infant Rhesus Macaques (Macaca mulatta)

PubMed Central

Gottlieb, Daniel H.; Capitanio, John P.

2012-01-01

The human intruder test is a testing paradigm designed to measure rhesus macaques’ behavioral responses to a stressful and threatening situation. In the test, an unfamiliar human positions him/herself in various threatening positions relative to a caged macaque. This paradigm has been utilized for over twenty years to measure a variety of behavioral constructs, including fear and anxiety, behavioral inhibition, emotionality, and aggression. To date there have been no attempts to evaluate comprehensively the structure of the behavioral responses to the test. Our first goal was to identify the underlying latent factors affecting the different responses among subjects, and our second goal was determine if rhesus reared in different environments respond differently in this testing paradigm. To accomplish this, we first performed exploratory and confirmatory factor analyses on the behavioral responses of 3–4 month-old rhesus macaques, utilizing data from over 2,000 separate tests conducted between 2001–2007. Using the resulting model, we then tested to see whether early rearing experience affected responses in the test. Our first analyses suggested that most of the variation in infant behavioral responses to the human intruder test could be explained by four latent factors: “Activity,” “Emotionality,” “Aggression,” and “Displacement.” Our second analyses revealed a significant effect of rearing condition for each factor score (P < 0.001); most notable socially-reared animals had the lowest Activity score (P < 0.001), indoor mother-reared animals had the highest Displacement score (P < 0.001), and nursery-reared animals had the highest Emotionality (P < 0.001) and lowest Aggression scores (P < 0.001). These results demonstrate that this standardized testing paradigm reveals multiple patterns of response, which are influenced by an animal’s rearing history. PMID:23229557

Latent variables affecting behavioral response to the human intruder test in infant rhesus macaques (Macaca mulatta).

PubMed

Gottlieb, Daniel H; Capitanio, John P

2013-04-01

The human intruder test is a testing paradigm designed to measure rhesus macaques' behavioral responses to a stressful and threatening situation. In the test, an unfamiliar human positions him/herself in various threatening positions relative to a caged macaque. This paradigm has been utilized for over 20 years to measure a variety of behavioral constructs, including fear and anxiety, behavioral inhibition, emotionality, and aggression. To date, there have been no attempts to evaluate comprehensively the structure of the behavioral responses to the test. Our first goal was to identify the underlying latent factors affecting the different responses among subjects, and our second goal was to determine if rhesus reared in different environments respond differently in this testing paradigm. To accomplish this, we first performed exploratory and confirmatory factor analyses on the behavioral responses of 3- to 4-month-old rhesus macaques, utilizing data from over 2,000 separate tests conducted between 2001-2007. Using the resulting model, we then tested to see whether early rearing experience affected responses in the test. Our first analyses suggested that most of the variation in infant behavioral responses to the human intruder test could be explained by four latent factors: "activity," "emotionality," "aggression," and "displacement." Our second analyses revealed a significant effect of rearing condition for each factor score (P < 0.001); most notable socially reared animals had the lowest activity score (P < 0.001), indoor mother-reared animals had the highest displacement score (P < 0.001), and nursery-reared animals had the highest emotionality (P < 0.001) and lowest aggression scores (P < 0.001). These results demonstrate that this standardized testing paradigm reveals multiple patterns of response, which are influenced by an animal's rearing history. © 2012 Wiley Periodicals, Inc.

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

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.

Endothelin receptors and activity differ in human, dog, and rabbit lung.

PubMed

McKay, K O; Armour, C L; Black, J L

1996-01-01

In this study, we have examined dog and rabbit airways as potential models for human airways in regard to the activity of endothelin. The receptors involved in the response to endothelin-1 (ET-1) in airway tissue from human, rabbit, and dog lung were investigated, as was the mechanism responsible for the contraction to ET-1 in tissue from the three species. By using specific endothelin receptor agonists and antagonists, we have demonstrated that ETB receptors predominate in rabbit and human airways and ETA receptors in dog airways. The contraction to ET-1 is not dependent on cyclooxygenase products of arachidonic acid, as indomethacin had no effect on the response to ET-1. Extracellular calcium influx via voltage-dependent channels is necessary for contraction to ET-1 in rabbit and dog airways. These results are in contrast to our previously reported results in human airways, in which neither removal of extracellular calcium nor verapamil affected the ET-1 response. The sustained phase of the contraction to ET-1 in all three species may be mediated in part by activation of protein kinase C (PKC), as the inhibitor staurosporine significantly altered the time course of the response to endothelin. We therefore conclude that in rabbit airways ET-1 activates ETB receptors, triggers the influx of extracellular calcium through voltage-dependent channels, and induces a contractile response that is, in part, dependent upon stimulation of PKC. The same mechanism is triggered in dog bronchus; however, the receptors involved in this species are of the ETA type. Finally, in human airways, the contractile response to ET-1, while independent of extracellular calcium influx, is dependent upon PKC activation after binding of the peptide to ETB receptors.

Human Temporal Cortical Single Neuron Activity During Working Memory Maintenance

PubMed Central

Zamora, Leona; Corina, David; Ojemann, George

2016-01-01

The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

Assessing the Impact of Human Activities on British Columbia’s Estuaries

PubMed Central

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. PMID:24937486

Variability of interferon-λ induction and antiviral activity in Nipah virus infected differentiated human bronchial epithelial cells of two human donors.

PubMed

Sauerhering, Lucie; Müller, Helena; Behner, Laura; Elvert, Mareike; Fehling, Sarah Katharina; Strecker, Thomas; Maisner, Andrea

2017-10-01

Highly pathogenic Nipah virus (NiV) generally causes severe encephalitis in humans. Respiratory symptoms are infrequently observed, likely reflecting variations in infection kinetics in human airways. Supporting this idea, we recently identified individual differences in NiV replication kinetics in cultured airway epithelia from different human donors. As type III interferons (IFN-λ) represent major players in the defence mechanism against viral infection of the respiratory mucosa, we studied IFN-λ induction and antiviral activity in NiV-infected primary differentiated human bronchial epithelial cells (HBEpCs) cultured under air-liquid interface conditions. Our studies revealed that IFN-λ was upregulated in airway epithelia upon NiV infection. We also show that IFN-λ pretreatment efficiently inhibited NiV replication. Interestingly, the antiviral activity of IFN-λ varied in HBEpCs from two different donors. Increased sensitivity to IFN-λ was associated with higher expression levels of IFN-λ receptors, enhanced phosphorylation of STAT1, as well as enhanced induction of interferon-stimulated gene expression. These findings suggest that individual variations in IFN-λ receptor expression affecting IFN responsiveness can play a functional role for NiV replication kinetics in human respiratory epithelial cells of different donors.

Human Activity Modeling and Simulation with High Biofidelity

DTIC Science & Technology

2013-01-01

Human activity Modeling and Simulation (M&S) plays an important role in simulation-based training and Virtual Reality (VR). However, human activity M...kinematics and motion mapping/creation; and (e) creation and replication of human activity in 3-D space with true shape and motion. A brief review is

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

Adhesives with different pHs: effect on the MTBS of chemically activated and light-activated composites to human dentin.

PubMed

Mallmann, André; de Melo, Renata Marques; Estrela, Verbênia; Pelogia, Fernanda; Campos, Laura; Bottino, Marco Antonio; Valandro, Luiz Felipe

2007-08-01

To evaluate the bond strength between human dentin and composites, using two light-activated single-bottle total-etch adhesive systems with different pHs combined with chemically activated and light-activated-composites. The tested hypothesis was that the dentin bond strength is not influenced by an adhesive system of low pH, combined with chemically activated or light-activated composites. Flat dentin surfaces of twenty-eight human third molars were allocated in 4 groups (n=7), depending on the adhesive system: (One Step Plus-OS and Prime & Bond NT-PB) and composite (light-activated Filtek Z-100 [Z100] and chemically activated Bisfil 2B [B2B]). Each adhesive system was applied on acid-etched dentin and then one of the composites was added to form a 5 mm-high resin block. The specimens were stored in tap water (37 degrees C/24 h) and sectioned into two axes, x and y. This was done with a diamond disk under coolant irrigation to obtain beams with a cross-section area of approximately 0.8 mm(2). Each specimen was then attached to a custom-made device and submitted to the microtensile test (1 mm*min-1). Data were analyzed using two-way ANOVA and Tukey's tests (p<0.05). The anticipated hypothesis was not confirmed (p<0.0001). The bond strengths (MPa) were not statistically different between the two adhesive systems when light-activated composite was used (OS+Z100 = 24.7+/-7.1 feminine; PB+Z100 = 23.8+/-5.7 feminine). However, with use of the chemically activated composite (B2B), PB (7.8+/-3.6b MPa) showed significantly lower dentin bond strengths than OS (32.2+/-7.6 feminine). The low pH of the adhesive system can affect the bond of chemically activated composite to dentin. On the other hand, under the present conditions, the low pH did not seem to affect the bond of light-activated composites to dentin significantly.

Anti-complement activities of human breast-milk.

PubMed

Ogundele, M O

1999-08-01

It has long been observed that the human milk possesses significant anti-inflammatory properties, while simultaneously protecting the infant against many intestinal and respiratory pathogens. There is, however, a paucity of information on the degree and extent of this anti-inflammatory activity. In the present study, the inhibitory effects of different fractions of human milk on serum complement activity were analysed. Colostrum and milk samples from healthy voluntary lactating donors at different postpartum ages were obtained and pooled normal human serum was used as source of complement in a modified CH50 assay. Inherent complement activity in human milk was also investigated by measuring the deposition of an activated C3 fragment on a serum-sensitive bacteria, and by haemolytic assays. Most whole- and defatted-milk samples consistently showed a dose-dependent inhibition of the serum complement activity. This inhibition was greater in mature milk compared to transitional milk samples. It was enhanced by inactivation of milk complement, and diminished by centrifugation of milk samples, which partly removed fat and larger protein components including casein micelles. Inherent complement activity in human milk was also demonstrated by haemolysis of sensitised sheep erythrocytes and deposition of C3 fragments on solid-phase bacteria. These activities were highest in the colostrum and gradually decreased as lactation proceeded. Several natural components abundant in the fluid phase of the human breast-milk have been shown to be inhibitors of complement activation in vitro. Their physiological significance probably reside in their ability to prevent inflammatory-induced tissue damage of the delicate immature gastrointestinal tract of the new-born as well as the mammary gland itself, which may arise from ongoing complement activation.

Effects of current physical activity on affective response to exercise: physical and social-cognitive mechanisms.

PubMed

Magnan, Renee E; Kwan, Bethany M; Bryan, Angela D

2013-01-01

Affective responses during exercise are often important determinants of exercise initiation and maintenance. Current physical activity may be one individual difference that is associated with the degree to which individuals have positive (or negative) affective experiences during exercise. The objective of this study was to explore physical and cognitive explanations of the relationship between current activity status (more versus less active) and affective response during a 30-minute bout of moderate-intensity exercise. Participants reported their current level of physical activity, exercise self-efficacy and affect during a 30-minute bout of moderate-intensity exercise. More active individuals experienced higher levels of positive affect and tranquillity and lower levels of negative affect and fatigue during exercise. Multivariate models for each affective state indicated separate processes through which physical activity may be associated with changes in affect during exercise. These models indicate that affect experienced during physical activity is related to the current activity level and these relationships can be partially explained by the physical and cognitive factors explored in this study. Recommendations for future research to elucidate whether positive affective response to physical activity improves as a function of becoming more active over time are discussed.

A human intermediate conductance calcium-activated potassium channel

PubMed Central

Ishii, Takahiro M.; Silvia, Christopher; Hirschberg, Birgit; Bond, Chris T.; Adelman, John P.; Maylie, James

1997-01-01

An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is ≈50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 μM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3.5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 μM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel. PMID:9326665

Influence of Sulforaphane Metabolites on Activities of Human Drug-Metabolizing Cytochrome P450 and Determination of Sulforaphane in Human Liver Cells.

PubMed

Vanduchova, Alena; Tomankova, Veronika; Anzenbacher, Pavel; Anzenbacherova, Eva

2016-12-01

The influence of metabolites of sulforaphane, natural compounds present in broccoli (Brassica oleracea var. botrytis italica) and in other cruciferous vegetables, on drug-metabolizing cytochrome P450 (CYP) enzymes in human liver microsomes and possible entry of sulforaphane into human hepatic cells were investigated. Metabolites studied are compounds derived from sulforaphane by the mercapturic acid pathway (conjugation with glutathione and by following reactions), namely sulforaphane glutathione and sulforaphane cysteine conjugates and sulforaphane-N-acetylcysteine. Their possible effect on four drug-metabolizing CYP enzymes, CYP3A4 (midazolam 1'-hydroxylation), CYP2D6 (bufuralol 1'-hydroxylation), CYP1A2 (7-ethoxyresorufin O-deethylation), and CYP2B6 (7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation), was tested. Inhibition of four prototypical CYP activities by sulforaphane metabolites was studied in pooled human liver microsomes. Sulforaphane metabolites did not considerably affect biological function of drug-metabolizing CYPs in human liver microsomes except for CYP2D6, which was found to be inhibited down to 73-78% of the original activity. Analysis of the entry of sulforaphane into human hepatocytes was done by cell disruption by sonication, methylene chloride extraction, and modified high-performance liquid chromatography method. The results have shown penetration of sulforaphane into the human hepatic cells.

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.

PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

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

Senthilkumar, P.K.; Robertson, L.W.; Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA

Polychlorinated biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cellmore » cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism. -- Highlights: ► Human immortal (HaCaT) and primary (NFK) keratinocytes were exposed to PCB153. ► PCB153 significantly reduced telomerase activity and telomere length in HaCaT. ► No effect on telomere length

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

2018-06-01

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.

Real-time Human Activity Recognition

NASA Astrophysics Data System (ADS)

Albukhary, N.; Mustafah, Y. M.

2017-11-01

The traditional Closed-circuit Television (CCTV) system requires human to monitor the CCTV for 24/7 which is inefficient and costly. Therefore, there’s a need for a system which can recognize human activity effectively in real-time. This paper concentrates on recognizing simple activity such as walking, running, sitting, standing and landing by using image processing techniques. Firstly, object detection is done by using background subtraction to detect moving object. Then, object tracking and object classification are constructed so that different person can be differentiated by using feature detection. Geometrical attributes of tracked object, which are centroid and aspect ratio of identified tracked are manipulated so that simple activity can be detected.

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.

Enhancing Human Spermine Synthase Activity by Engineered Mutations

PubMed Central

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. PMID:23468611

Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

PubMed Central

Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

2012-01-01

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current IClswell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The IClswell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates IClswell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on

Effects of current physical activity on affective response to exercise: Physical and social-cognitive mechanisms

PubMed Central

Magnan, Renee E.; Kwan, Bethany M.; Bryan, Angela D.

2012-01-01

Objective Affective responses during exercise are often important determinants of exercise initiation and maintenance. Current physical activity may be one individual difference that is associated with the degree to which individuals have positive (or negative) affective experiences during exercise. The objective of this investigation was to explore physical and cognitive explanations of the relationship between current activity status (more versus less active) and affective response during a 30-minute bout of moderate-intensity exercise. Method Participants reported their current level of physical activity, exercise self-efficacy, and affect during a 30-minute bout of moderate-intensity exercise. Results More active individuals experienced higher levels of positive affect and tranquility and lower levels of negative affect and fatigue during exercise. Multivariate models for each affective state indicated separate processes through which physical activity may be associated with changes in affect during exercise. Conclusions These models indicate that affect experienced during physical activity is related to current activity level and these relationships can be partially explained by the physical and cognitive factors explored in this study. Recommendations for future research to elucidate whether positive affective response to physical activity improves as a function of becoming more active over time are discussed. PMID:23088712

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.

Solar and geomagnetic activity, extremely low frequency magnetic and electric fields and human health at the Earth's surface

NASA Astrophysics Data System (ADS)

Palmer, S. J.; Rycroft, M. J.; Cermack, M.

2006-09-01

The possibility that conditions on the Sun and in the Earth’s magnetosphere can affect human health at the Earth’s surface has been debated for many decades. This work reviews the research undertaken in the field of heliobiology, focusing on the effect of variations of geomagnetic activity on human cardiovascular health. Data from previous research are analysed for their statistical significance, resulting in support for some studies and the undermining of others. Three conclusions are that geomagnetic effects are more pronounced at higher magnetic latitudes, that extremely high as well as extremely low values of geomagnetic activity seem to have adverse health effects and that a subset of the population (10-15%) is predisposed to adverse health due to geomagnetic variations. The reported health effects of anthropogenic sources of electric and magnetic fields are also briefly discussed, as research performed in this area could help to explain the results from studies into natural electric and magnetic field interactions with the human body. Possible mechanisms by which variations in solar and geophysical parameters could affect human health are discussed and the most likely candidates investigated further. Direct effects of natural ELF electric and magnetic fields appear implausible; a mechanism involving some form of resonant absorption is more likely. The idea that the Schumann resonance signals could be the global environmental signal absorbed by the human body, thereby linking geomagnetic activity and human health is investigated. Suppression of melatonin secreted by the pineal gland, possibly via desynchronised biological rhythms, appears to be a promising contender linking geomagnetic activity and human health. There are indications that calcium ions in cells could play a role in one or more mechanisms. It is found to be unlikely that a single mechanism can explain all of the reported phenomena.

Different parameter and technique affecting the rate of evaporation on active solar still -a review

NASA Astrophysics Data System (ADS)

A, Muthu Manokar; D, Prince Winston; A. E, Kabeel; Sathyamurthy, Ravishankar; T, Arunkumar

2018-03-01

Water is one of the essential sources for the endurance of human on the earth. As earth having only a small amount of water resources for consumption purpose people in rural and urban areas are getting affected by consuming dirty water that leads to water-borne diseases. Even though ground water is available in small quantity, it has to be treated properly before its use for internal consumption. Brackish water contains dissolve and undissolved contents, and hence it is not suitable for the household purpose. Nowadays, distillation process is done by using passive and active solar stills. The major problem in using passive solar still is meeting higher demand for fresh water. The fresh water production from passive solar still is critically low to meet the demand. To improve the productivity of conventional solar still, input feed water is preheated by integrating the solar still to different collector panels. In this review article, the different parameters that affect the rate of evaporation in an active solar still and the different methods incorporated has been presented. In addition to active distillation system, forced convection technique can be incorporated to increase the yield of fresh water by decreasing the temperature of cover. Furthermore, it is identified that the yield of fresh water from the active desalination system can be improved by sensible and latent heat energy storage. This review will motivate the researchers to decide appropriate active solar still technology for promoting development.

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

Cancer Activation and Polymorphisms of Human Cytochrome P450 1B1

PubMed Central

Chun, Young-Jin; Kim, Donghak

2016-01-01

Human cytochrome P450 enzymes (P450s, CYPs) are major oxidative catalysts that metabolize various xenobiotic and endogenous compounds. Many carcinogens induce cancer only after metabolic activation and P450 enzymes play an important role in this phenomenon. P450 1B1 mediates bioactivation of many procarcinogenic chemicals and carcinogenic estrogen. It catalyzes the oxidation reaction of polycyclic aromatic carbons, heterocyclic and aromatic amines, and the 4-hydroxylation reaction of 17β-estradiol. Enhanced expression of P450 1B1 promotes cancer cell proliferation and metastasis. There are at least 25 polymorphic variants of P450 1B1 and some of these have been reported to be associated with eye diseases. In addition, P450 1B1 polymorphisms can greatly affect the metabolic activation of many procarcinogenic compounds. It is necessary to understand the relationship between metabolic activation of such substances and P450 1B1 polymorphisms in order to develop rational strategies for the prevention of its toxic effect on human health. PMID:27123158

Thalidomide inhibits inflammatory and angiogenic activation of human intestinal microvascular endothelial cells (HIMEC).

PubMed

Rafiee, Parvaneh; Stein, Daniel J; Nelson, Victoria M; Otterson, Mary F; Shaker, Reza; Binion, David G

2010-02-01

The glutamic acid derivative thalidomide is a transcriptional inhibitor of TNF-alpha but is also known to affect human blood vessels, which may underlie its teratogenicity. Thalidomide has been used in the treatment of refractory Crohn's disease (CD), but the therapeutic mechanism is not defined. We examined the effect of thalidomide on primary cultures of human intestinal microvascular endothelial cells (HIMEC), the relevant endothelial cell population in inflammatory bowel disease (IBD), to determine its effect on endothelial activation, leukocyte interaction, and VEGF-induced angiogenesis. HIMEC cultures were pretreated with thalidomide before activation with either TNF-alpha/LPS or VEGF. A low-shear-stress flow adhesion assay with either U-937 or whole blood was used to assess HIMEC activation following TNF-alpha/LPS, and a Wright's stain identified adherent leukocytes. Expression of cell adhesion molecules (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) was assessed using radioimmunoassay. Effects of thalidomide on NF-kappaB activation, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression in TNF-alpha/LPS-activated HIMEC were determined by RT-PCR and Western blotting. Thalidomide blocked adhesion of both U-937 and whole blood leukocytes by 50% in HIMEC, inhibiting binding of all classes of leukocytes. Thalidomide also blocked NF-kappaB and cell adhesion molecule expression in HIMEC. In marked contrast, thalidomide did not affect either iNOS or COX-2 expression, two key molecules that play a role in the downregulation of HIMEC activation. VEGF-induced HIMEC transmigration, growth, proliferation, tube formation, and Akt phosphorylation were significantly inhibited by thalidomide. In summary, thalidomide exerted a potent effect on HIMEC growth and activation, suggesting that it may also function via an endothelial mechanism in the treatment of CD.

Thalidomide inhibits inflammatory and angiogenic activation of human intestinal microvascular endothelial cells (HIMEC)

PubMed Central

Stein, Daniel J.; Nelson, Victoria M.; Otterson, Mary F.; Shaker, Reza; Binion, David G.

2010-01-01

The glutamic acid derivative thalidomide is a transcriptional inhibitor of TNF-α but is also known to affect human blood vessels, which may underlie its teratogenicity. Thalidomide has been used in the treatment of refractory Crohn's disease (CD), but the therapeutic mechanism is not defined. We examined the effect of thalidomide on primary cultures of human intestinal microvascular endothelial cells (HIMEC), the relevant endothelial cell population in inflammatory bowel disease (IBD), to determine its effect on endothelial activation, leukocyte interaction, and VEGF-induced angiogenesis. HIMEC cultures were pretreated with thalidomide before activation with either TNF-α/LPS or VEGF. A low-shear-stress flow adhesion assay with either U-937 or whole blood was used to assess HIMEC activation following TNF-α/LPS, and a Wright's stain identified adherent leukocytes. Expression of cell adhesion molecules (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) was assessed using radioimmunoassay. Effects of thalidomide on NF-κB activation, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression in TNF-α/LPS-activated HIMEC were determined by RT-PCR and Western blotting. Thalidomide blocked adhesion of both U-937 and whole blood leukocytes by 50% in HIMEC, inhibiting binding of all classes of leukocytes. Thalidomide also blocked NF-κB and cell adhesion molecule expression in HIMEC. In marked contrast, thalidomide did not affect either iNOS or COX-2 expression, two key molecules that play a role in the downregulation of HIMEC activation. VEGF-induced HIMEC transmigration, growth, proliferation, tube formation, and Akt phosphorylation were significantly inhibited by thalidomide. In summary, thalidomide exerted a potent effect on HIMEC growth and activation, suggesting that it may also function via an endothelial mechanism in the treatment of CD. PMID:19926820

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.

The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity.

PubMed

Alcaro, Antonio; Carta, Stefano; Panksepp, Jaak

2017-01-01

Psychologists usually considered the "Self" as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potential forms. According to Jung, the Self originates from an inborn dynamic structure integrating the essential drives of our "brain-mind," and leading both to instinctual behavioral actions and to archetypal psychological experiences. Interestingly, recent neuroethological studies indicate that our subjective identity rests on ancient neuropsychic processes that humans share with other animals as part of their inborn constitutional repertoire. Indeed, brain activity within subcortical midline structures (SCMSs) is intrinsically related to the emergence of prototypical affective states, that not only influence our behavior in a flexible way, but alter our conscious field, giving rise to specific feelings or moods, which constitute the first form of self-orientation in the world. Moreover, such affective dynamics play a central role in the organization of individual personality and in the evolution of all other (more sophisticated) psychological functions. Therefore, on the base of the convergence between contemporary cutting-edge scientific research and some psychological intuitions of Jung, we intend here to explore the first neuroevolutional layer of human mind, that we call the affective core of the Self.

The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity

PubMed Central

Alcaro, Antonio; Carta, Stefano; Panksepp, Jaak

2017-01-01

Psychologists usually considered the “Self” as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potential forms. According to Jung, the Self originates from an inborn dynamic structure integrating the essential drives of our “brain–mind,” and leading both to instinctual behavioral actions and to archetypal psychological experiences. Interestingly, recent neuroethological studies indicate that our subjective identity rests on ancient neuropsychic processes that humans share with other animals as part of their inborn constitutional repertoire. Indeed, brain activity within subcortical midline structures (SCMSs) is intrinsically related to the emergence of prototypical affective states, that not only influence our behavior in a flexible way, but alter our conscious field, giving rise to specific feelings or moods, which constitute the first form of self-orientation in the world. Moreover, such affective dynamics play a central role in the organization of individual personality and in the evolution of all other (more sophisticated) psychological functions. Therefore, on the base of the convergence between contemporary cutting-edge scientific research and some psychological intuitions of Jung, we intend here to explore the first neuroevolutional layer of human mind, that we call the affective core of the Self. PMID:28919868

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.

Separating the impacts of climate change and human activities on streamflow: A review of methodologies and critical assumptions

NASA Astrophysics Data System (ADS)

Dey, Pankaj; Mishra, Ashok

2017-05-01

Climate change and human activity are two major drivers that alter hydrological cycle processes and cause change in spatio-temporal distribution of water availability. Streamflow, the most important component of hydrological cycle undergoes variation which is expected to be influenced by climate change as well as human activities. Since these two affecting conditions are time dependent, having unequal influence, identification of the change point in natural flow regime is of utmost important to separate the individual impact of climate change and human activities on streamflow variability. Subsequently, it is important as well for framing adaptation strategies and policies for regional water resources planning and management. In this paper, a comprehensive review of different approaches used by research community to isolate the impacts of climate change and human activities on streamflow are presented. The important issues pertaining to different approaches, to make rational use of methodology, are discussed so that researcher and policymaker can understand the importance of individual methodology and its use in water resources management. A new approach has also been suggested to select a representative change point under different scenarios of human activities with incorporation of climate variability/change.

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.

Threats and changes affecting human relationships with wilderness: Implications for management

Treesearch

Robert G. Dvorak; William T. Borrie; Alan E. Watson

2011-01-01

For wilderness managers, the ability to recognize threats and changing conditions is vital. While these threats are typically associated with resource and social conditions, they can also be investigated relative to wilderness relationships. This paper explores how threats and changes may be affecting human relationships with wilderness and the possible implications...

High School Students' Affective Reaction to English Speaking Activities

ERIC Educational Resources Information Center

Jorquera Torres, Oliver Camilo; Mendoza Zapata, Jhon Eliot; Díaz Larenas, Claudio Heraldo

2017-01-01

This study aims to measure fifty-two high school students' affective reactions after doing individual and pair-based speaking activities then completing a semantic differential scale of nine bipolar adjectives. Results do not show significant statistical differences between the two types of activities or the schools involved in this study, but…

Affective decision-making and externalizing behaviors: the role of autonomic activity.

PubMed

Bubier, Jennifer L; Drabick, Deborah A G

2008-08-01

We tested a conceptual model involving the inter-relations among affective decision-making (indexed by a gambling task), autonomic nervous system (ANS) activity, and attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in a largely impoverished, inner city sample of first through third grade children (N=63, 54% male). The present study hypothesized that impaired affective decision-making and decreased sympathetic and parasympathetic activation would be associated with higher levels of ADHD and ODD symptoms, and that low sympathetic and parasympathetic activation during an emotion-inducing task would mediate the relation between affective decision-making and child externalizing symptoms. In support of our model, disadvantageous decision-making on a gambling task was associated with ADHD hyperactivity/impulsivity symptoms among boys, and attenuated sympathetic activation during an emotion-inducing task mediated this relation. Support for the model was not found among girls.

Patient and disease factors affecting the choice and adherence to active surveillance.

PubMed

Dall'Era, Marc A

2015-05-01

Treatment decisions for low-risk prostate cancer are arguably some of the most challenging in oncology. Active surveillance has emerged as an important option for many men with tumors estimated to have a low metastatic potential. Multiple complex patient and physician factors affect the recommendation, selection, and adherence to active surveillance. While baseline clinical criteria are used to identify candidates for this approach, it is important to identify and understand other forces that may influence the management of prostate cancer with active surveillance. Patient perceptions and acceptance of active surveillance have improved over time. Treatment decisions for prostate cancer are strongly associated with physician recommendations, and a high-quality relationship between the patient and his healthcare system is critical to successful active surveillance. Patient understanding of prostate cancer and consistency of information received from separate physicians can affect a decision to pursue active surveillance. Psychological symptoms, most notably regarding anxiety and distress, can affect adherence to active surveillance over time. In general, anxiety for men on active surveillance is low, and lifestyle interventions and self-management strategies may be helpful for increasing quality of life and limiting abandonment of active surveillance in the absence of disease progression. Multiple factors may affect the decision for and adherence to active surveillance for prostate cancer. It is important for both physicians and patients to be aware of these issues and work towards individualized approaches and interventions as needed to increase adoption of active surveillance in the future.

Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans

PubMed Central

Byrne, Loretta M.; Yu, Chang; Wang, Thomas J.; Brown, Nancy J.

2014-01-01

Context: Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear. Objective: To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans. Design: We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet. Setting: Academic clinical research center. Participants: Healthy, nondiabetic, normotensive volunteers. Interventions: Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5–7 days. Main Outcome Measures: Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle. Results: A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (−16.0 ± 5.6%; P = .007) and C-peptide responses (−21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (−1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion. Conclusions: Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity. PMID:25029426

Physical characteristics of indigestible solids affect emptying from the fasting human stomach.

PubMed Central

Meyer, B; Beglinger, C; Neumayer, M; Stalder, G A

1989-01-01

Gastric emptying of indigestible solids depends on their size. It is not clear whether physical characteristics other than particle size affect emptying of indigestible solids from the fasting human stomach. We studied gastric emptying of three differently shaped particles, (cubes, spheres, rods) of either hard or soft consistency during the fasting state in human volunteers. The shape of indigestible particles did not affect their emptying. The area under the gastric emptying curve (AUC: particles x hour) was for hard cubes 24.7 (2.2), for hard spheres 27.9 (1.6), for hard rods 26.9 (2.7). All soft particles emptied faster than their identically shaped hard counterparts, but there was no difference among the three shapes (AUC for soft cubes: 29.2 (3.0), for soft spheres 32.0 (1.8), for soft rods 34.1 (1.2). If gastric emptying of hard and soft particles was compared independently of their shape, soft particles emptied significantly faster than hard ones: AUC 31.8 (1.2) v 26.5 (1.3) (p less than 0.01). In conclusion, the consistency but not the shape significantly affects gastric emptying. Specific physical characteristics other than size and shape may affect gastric emptying of indigestible particles which may be of importance in the design of drugs. PMID:2599438

Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity

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

Herr, Michael J.; Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163; Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163

2014-05-16

Highlights: • CD9 is differentially expressed in human Burkitt’s lymphoma cells. • We found that CD9 expression promotes these cells proliferation. • CD9 expression also increases HDAC activity. • HDAC inhibition decreased both cell proliferation and importantly CD9 expression. • CD9 may dictate HDAC efficacy and play a role in HDAC regulation. - Abstract: Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in twomore » human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9–Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity.« less

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

PubMed

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Previous studies have linked angiotensin-converting enzyme ( ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O 2 consumption (VO 2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two -way repeated-measures ANOVA were used. In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO 2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD

Biofidelic Human Activity Modeling and Simulation with Large Variability

DTIC Science & Technology

2014-11-25

A systematic approach was developed for biofidelic human activity modeling and simulation by using body scan data and motion 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...that can replicate a human activity in 3D space with the true shape and true motion of a human. Using this approach, a model library was built to

The proteinase-activated receptor-2 mediates phagocytosis in a Rho-dependent manner in human keratinocytes.

PubMed

Scott, Glynis; Leopardi, Sonya; Parker, Lorelle; Babiarz, Laura; Seiberg, Miri; Han, Rujiing

2003-09-01

Recent work shows that the G-protein-coupled receptor proteinase activated receptor-2 activates signals that stimulate melanosome uptake in keratinocytes in vivo and in vitro. The Rho family of GTP-binding proteins is involved in cytoskeletal remodeling during phagocytosis. We show that proteinase-activated receptor-2 mediated phagocytosis in human keratinocytes is Rho dependent and that proteinase-activated receptor-2 signals to activate Rho. In contrast, Rho activity did not affect either proteinase-activated receptor-2 activity or mRNA and protein levels. We explored the signaling mechanisms of proteinase-activated receptor-2 mediated Rho activation in human keratinocytes and show that activation of proteinase-activated receptor-2, either through specific proteinase-activated receptor-2 activating peptides or through trypsinization, elevates cAMP in keratinocytes. Proteinase-activated receptor-2 mediated Rho activation was pertussis toxin insensitive and independent of the protein kinase A signaling pathway. These data are the first to show that proteinase-activated receptor-2 mediated phagocytosis is Rho dependent and that proteinase-activated receptor-2 signals to Rho and cAMP in keratinocytes. Because phagocytosis of melanosomes is recognized as an important mechanism for melanosome transfer to keratinocytes, these results suggest that Rho is a critical signaling intermediate in melanosome uptake in keratinocytes.

[Effect of hydrochemistry characteristics under impact of human activity: a case study in the upper reaches of the Xijiang River basin].

PubMed

Yu, Shil; Sun, Ping-an; Du, Wen-yue; He, Shi-yi; Li, Rui

2015-01-01

In this paper, observation and sampling were taken three times a month in a hydrological year for three typical sections of the middle and upper reaches of the Xijiang River basin, based on the data of hydrochemistry and flow, the article mainly discusses the evolution process of hydrochemistry in river under natural process and impact of human activity. Hydrochemical characteristics of 116. samples were analyzed in the study area. The hydrochemistry type in the middle and upper reaches of the Xijiang River basin belonged to HCO3- -Ca2+ type, and the chemical weathering type mainly came from carbonate rock weathering. Ca2+ and HCO3- were the main cations and anions, which reflected that hydrochemical characteristics of river in karst area mainly affected by the dissolution of carbonate rock. Na, Mg2, Ca2+ and Cl- mainly affected by natural conditions, the impact of human activity was little. K+, NO3-, SO4(2-) and HCO3- were affected by human activity in different degrees, and it showed different influence ways. This study had an important significance for the change of river hydrochemistry, water quality characteristics, and the effect on substance transported fluxes in the downstream of Pearl River and water quality protection in South China Monsoon Area.

Proteome Analysis of Human Sebaceous Follicle Infundibula Extracted from Healthy and Acne-Affected Skin

PubMed Central

Bek-Thomsen, Malene; Lomholt, Hans B.; Scavenius, Carsten; Enghild, Jan J.; Brüggemann, Holger

2014-01-01

Acne vulgaris is a very common disease of the pilosebaceous unit of the human skin. The pathological processes of acne are not fully understood. To gain further insight sebaceous follicular casts were extracted from 18 healthy and 20 acne-affected individuals by cyanoacrylate-gel biopsies and further processed for mass spectrometry analysis, aiming at a proteomic analysis of the sebaceous follicular casts. Human as well as bacterial proteins were identified. Human proteins enriched in acne and normal samples were detected, respectively. Normal follicular casts are enriched in proteins such as prohibitins and peroxiredoxins which are involved in the protection from various stresses, including reactive oxygen species. By contrast, follicular casts extracted from acne-affected skin contained proteins involved in inflammation, wound healing and tissue remodeling. Among the most distinguishing proteins were myeloperoxidase, lactotransferrin, neutrophil elastase inhibitor and surprisingly, vimentin. The most significant biological process among all acne-enriched proteins was ‘response to a bacterium’. Identified bacterial proteins were exclusively from Propionibacterium acnes. The most abundant P. acnes proteins were surface-exposed dermatan sulphate adhesins, CAMP factors, and a so far uncharacterized lipase in follicular casts extracted from normal as well as acne-affected skin. This is a first proteomic study that identified human proteins together with proteins of the skin microbiota in sebaceous follicular casts. PMID:25238151

Does Human Migration Affect International Trade? A Complex-Network Perspective

PubMed Central

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 pairs of countries that are more central in the migration network trade more. We show that: (i) the networks of international migration and trade are strongly correlated, and such correlation can be mostly explained by country economic/demographic size and geographical distance; (ii) centrality in the international-migration network boosts bilateral trade; (iii) intensive forms of country centrality are more trade enhancing than their extensive counterparts. 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. PMID:24828376

Trehalose does not affect the functions of human neutrophils in vitro.

PubMed

Tanaka, Koji; Kawamura, Mikio; Otake, Kohei; Toiyama, Yuji; Okugawa, Yoshinaga; Inoue, Yasuhiro; Uchida, Keiichi; Araki, Toshimitsu; Mohri, Yasuhiko; Kusunoki, Masato

2014-02-01

Trehalose, naturally occurring disaccharide, has been reported to prevent postoperative abdominal adhesions in animal models. We investigated whether trehalose affects the function of human polymorphonuclear neutrophils (PMNs) in vitro to assess the feasibility of its clinical application as an anti-adhesive barrier. Human PMNs were obtained from 17 healthy volunteers. Escherichia coli and Staphylococcus aureus were used for the bacterial infection model, whereas lipopolysaccharide (LPS) and interleukin (IL)-1β were used for inflammation induction model. The PMN phagocytosis rates of bacteria and apoptosis/necrosis were assessed on trehalose, maltose, and control media. Cytokines; namely, tumor necrosis factor-α, IL-1α, IL-1Ra, IL-6, and IL-8; and PMN-elastase were measured on each medium in both models. There were no significant differences in the phagocytosis rates, apoptosis/necrosis rates, or levels of all cytokines or PMN-elastase among the three media in the bacterial infection model. There were also no significant differences in the levels of all cytokines and PMN-elastase among the three media in the IL-1β inflammation induction model. PMN-elastase was lower in trehalose and maltose medium after LPS stimulation, at 3 and 24 h. Our results suggest that trehalose does not affect the cellular function, cytokine production, or release of PMN-elastase of human PMNs in an in vitro bacterial infection model.

Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

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

Schallreuter, Karin U.; Institute for Pigmentary Disorders in Association with EM Arndt University of Greifswald; University of Bradford

The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10{sup -3}M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. {sup 45}Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H{sub 2}O{sub 2}-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m{sup 2} surfacemore » area with its calcium gradient in the 10{sup -3}M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue.« less

Human Natural Killer Cells Exhibit Direct Activity Against Aspergillus fumigatus Hyphae, But Not Against Resting Conidia

PubMed Central

Schmidt, Stanislaw; Tramsen, Lars; Hanisch, Mitra; Latgé, Jean-Paul; Huenecke, Sabine; Koehl, Ulrike

2011-01-01

Because natural killer (NK) cells kill tumor cells and combat infections, there is growing interest in adoptively transferring NK cells to hematopoietic stem cell recipients. Unfortunately, in humans, the activity of NK cells against Aspergillus species, the major cause of invasive fungal infection in stem cell recipients, are poorly characterized. Our results show that unstimulated and interleukin-2 prestimulated human NK cells kill Aspergillus fumigatus hyphae but do not affect resting conidia. Killing is also induced by the supernatant of prestimulated NK cells and human perforin. The high levels of interferon-γ and granulocyte macrophage colony-stimulating factor produced by prestimulated NK cells are significantly reduced by Aspergillus, indicating an immunosuppressive effect of the fungus. Whereas Aspergillus hyphae activate NK cells, resting, and germinating, conidia and conidia of ΔrodA mutants lacking the hydrophobic surface layer do not. Our results suggest that adoptively transferred human NK cells may be a potential antifungal tool in the transplantation context. PMID:21208932

Zooming into daily life: within-person associations between physical activity and affect in young adults.

PubMed

Haas, Petra; Schmid, Johanna; Stadler, Gertraud; Reuter, Merle; Gawrilow, Caterina

2017-05-01

Negative affect in daily life is linked to poorer mental and physical health. Activity could serve as an effective, low-cost intervention to improve affect. However, few prior studies have assessed physical activity and affect in everyday life, limiting the ecological validity of prior findings. This study investigates whether daily activity is associated with negative and positive evening affect in young adults. Young adults (N = 189, Mdn = 23.00) participated in an intensive longitudinal study over 10 consecutive days. Participants wore accelerometers to objectively assess moderate-to-vigorous physical activity continuously throughout the day and reported their affect in time-stamped online evening diaries before going to sleep. On days when participants engaged in more activity than usual, they reported not only less depressed and angry evening affect but also more vigour and serenity in the evening. Young adults showed both less negative and more positive affect on days with more activity. Physical activity is a promising health promotion strategy for physical and mental well-being.

Using activity triggered e-diaries to reveal the associations between physical activity and affective states in older adult's daily living.

PubMed

Kanning, Martina; Ebner-Priemer, Ulrich; Schlicht, Wolfgang

2015-09-17

Evidence suggests that older adults show positive affects after participating in exercise bouts. However, it is less clear, if and how physical activities in daily living enhance affective states, too. This is dissatisfying, as most of older adults' physical activities are part of their daily living. To answer these questions we used activity-triggered e-diaries to investigate the within-subject effects of physical activity on three dimensions of affective states (valence, energetic arousal, calmness) during everyday life. Older adults (N = 74) between 50 and 70 years took part in the study during three consecutive days. Physical activity in daily living was objectively assessed using accelerometers. Affects were measured 10 min after a study participant surpassed a predefined threshold for activity or inactivity. The participants were prompted by an acoustic signal to assess their momentary affective states on an e-diary. Data were analyzed with hierarchical multilevel analyses. Whenever older individuals were more physically active, they felt more energized (energetic arousal) and agitated (calmness). However, they did not feel better (valence). Interestingly, body mass index (BMI) and valence were associated in a significant cross-level interaction. BMI acts as a moderating variable in the way that lower BMI scores were associated with higher levels of valence scores after being physically active. The innovative ambulatory assessment used here affords an interesting insight to the affective effects of daily activity of older adults. These effects are no simple and no linear ones, i.e. physical activity is not associated with positive affects per se as shown several times in experimental studies with single activity bouts. Rather there is a differentiating association seen as an enhanced feeling of energy and agitation, which is not accompanied by a better feeling. Socio-emotional selectivity theory may support the finding that older individuals are

Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

NASA Astrophysics Data System (ADS)

Legler, Patricia; Boisvert, Susanne; Compton, Jaimee; Millard, Charles

2014-07-01

We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleophilic serine O?. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its kcat/Km for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. pNBE was tested as a surrogate scaffold for mammalian esterases. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H) did not confer detectable OP hydrolase activity on human carboxylesterase 1. We discuss the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.

Sex differences in amygdala activation during the perception of facial affect.

PubMed

Killgore, W D; Yurgelun-Todd, D A

2001-08-08

The cognitive and affective systems of the cerebral cortex are often more lateralized in males than females, but it is unclear whether these differences extend to subcortical systems. We used fMRI to examine sex differences in lateralized amygdala activity during happy and fearful face perception. Amygdala activation differed for men and women depending on the valence of the expression. Overall, males were more lateralized than females, but the direction differed between valence conditions. Happy faces produced greater right than left amygdala activation for males but not females. Both sexes showed greater left amygdala activation for fearful faces. These findings suggest that the lateralization of affective function may extend beyond the cortex to subcortical regions such as the amygdala.

Momentary assessment of affect, physical feeling states, and physical activity in children.

PubMed

Dunton, Genevieve F; Huh, Jimi; Leventhal, Adam M; Riggs, Nathaniel; Hedeker, Donald; Spruijt-Metz, Donna; Pentz, Mary Ann

2014-03-01

Most research on the interplay of affective and physical feelings states with physical activity in children has been conducted under laboratory conditions and fails to capture intraindividual covariation. The current study used Ecological Momentary Assessment (EMA) to bidirectionally examine how affective and physical feeling states are related to objectively measured physical activity taking place in naturalistic settings during the course of children's everyday lives. Children (N = 119, ages 9-13 years, 52% male, 32% Hispanic) completed 8 days of EMA monitoring, which measured positive affect (PA), negative affect (NA), feeling tired, and feeling energetic up to 7 times per day. EMA responses were time-matched to accelerometer assessed moderate-to-vigorous physical activity (MVPA) in the 30 min before and after each EMA survey. Higher ratings of feeling energetic and lower ratings of feeling tired were associated with more MVPA in the 30 min after the EMA prompt. More MVPA in the 30 min before the EMA prompt was associated with higher ratings of PA and feeling energetic and lower ratings of NA. Between-subjects analyses indicated that mean hourly leisure-time MVPA was associated with less intraindividual variability in PA and NA. Physical feeling states predict subsequent physical activity levels, which in turn, predict subsequent affective states in children. Active children demonstrated higher positive and negative emotional stability. Although the strength of these associations were of modest magnitude and their clinical relevance is unclear, understanding the antecedents to and consequences of physical activity may have theoretical and practical implications for the maintenance and promotion of physical activity and psychological well-being in children. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Positive Affect and Inflammatory Activity in Breast Cancer Survivors: Examining the Role of Affective Arousal

PubMed Central

Moreno, Patricia I.; Moskowitz, Andrew L.; Ganz, Patricia A.; Bower, Julienne E.

2016-01-01

Objective Given the importance of positive affect and inflammation for well-being in cancer survivors, the current study examined the relationship between high and low arousal positive affect and inflammation in 186 women who completed treatment for early-stage breast cancer. Methods Measures of high and low arousal positive affect were completed within three months after treatment completion (baseline). Plasma markers of inflammation, including sTNF-RII, CRP, and IL-1ra, were assessed at baseline and 6 and 12 month follow-up assessments. Results Multilevel modeling analyses showed that high arousal positive affect was associated with lower levels of sTNF-RII, a marker of TNF activity, at treatment completion and prospectively predicted maintenance of these differences through the 6 and 12 month follow-ups controlling for biobehavioral confounds (b = −.055, t(156) = −2.40, p = .018). However, this association was no longer significant when controlling for fatigue. Exploratory analyses showed that low arousal positive affect was associated with lower levels of CRP at treatment completion and through the 6 and 12 month follow-ups; this association remained significant controlling for fatigue and other confounds (b = −.217, t(152) = −2.04, p = .043). Conclusion The relationship of high arousal positive affect (e.g., “active”) with sTNF-RII appears to be driven by the overlap of high arousal positive affect with fatigue while the relationship of low arousal positive affect (e.g., “calm”) with CRP was independent of fatigue. Future research should consider affective arousal when examining the association of positive affect with inflammation as this facet of positive affect may have important implications for interpretation of results. PMID:26867077

The abundance and variety of carbohydrate-active enzymes in the human gut microbiota.

PubMed

El Kaoutari, Abdessamad; Armougom, Fabrice; Gordon, Jeffrey I; Raoult, Didier; Henrissat, Bernard

2013-07-01

Descriptions of the microbial communities that live on and in the human body have progressed at a spectacular rate over the past 5 years, fuelled primarily by highly parallel DNA-sequencing technologies and associated advances in bioinformatics, and by the expectation that understanding how to manipulate the structure and functions of our microbiota will allow us to affect health and prevent or treat diseases. Among the myriad of genes that have been identified in the human gut microbiome, those that encode carbohydrate-active enzymes (CAZymes) are of particular interest, as these enzymes are required to digest most of our complex repertoire of dietary polysaccharides. In this Analysis article, we examine the carbohydrate-digestive capacity of a simplified but representative mini-microbiome in order to highlight the abundance and variety of bacterial CAZymes that are represented in the human gut microbiota.

Fire, Climate, and Human Activity: A Combustive Combination

NASA Astrophysics Data System (ADS)

Kehrwald, N. M.; Battistel, D.; Argiriadis, E.; Barbante, C.; Barber, L. B.; Fortner, S. K.; Jasmann, J.; Kirchgeorg, T.; Zennaro, P.

2017-12-01

Ice and lake core records demonstrate that fires caused by human activity can dominate regional biomass burning records in the Common Era. These major increases in fires are often associated with extensive land use change such as an expansion in agriculture. Regions with few humans, relatively stable human populations and/or unvarying land use often have fire histories that are dominated by climate parameters such as temperature and precipitation. Here, we examine biomass burning recorded in ice cores from northern Greenland (NEEM, (77°27'N; 51°3.6'W), Alaska (Juneau Icefield, 58° 35' N; 134° 29'W) and East Antarctica (EPICA DOME C; 75°06'S; 123°21'E), along with New Zealand lake cores to investigate interactions between climate, fire and human activity. Biomarkers such as levoglucosan, and its isomers mannosan and galactosan, can only be produced by cellulose combustion and therefore are specific indicators of past fire activity archived in ice and lake cores. These fire histories add another factor to climate proxies from the same core, and provide a comparison to regional fire syntheses from charcoal records and climate models. For example, fire data from the JSBACH-Spitfire model for the past 2000 years demonstrates that a climate-only scenario would not increase biomass burning in high northern latitudes for the past 2000 years, while NEEM ice core and regional pollen records demonstrate both increased fire activity and land use change that may be ascribed to human activity. Additional biomarkers such as fecal sterols in lake sediments can determine when people were in an area, and can help establish if an increased human presence in an area corresponds with intensified fire activity. This combination of specific biomarkers, other proxy data, and model output can help determine the relative impact of humans versus climate factors on regional fire activity.

Valproic Acid Induces Hair Regeneration in Murine Model and Activates Alkaline Phosphatase Activity in Human Dermal Papilla Cells

PubMed Central

Lee, Soung-Hoon; Yoon, Juyong; Shin, Seung Ho; Zahoor, Muhamad; Kim, Hyoung Jun; Park, Phil June; Park, Won-Seok; Min, Do Sik; Kim, Hyun-Yi; Choi, Kang-Yell

2012-01-01

Background Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo. Methodology/ Principal Findings Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP). VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl2 also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice. Conclusions/ Significance Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth. PMID:22506014

Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

PubMed

Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

2016-03-01

Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

The human factor: behavioral and neural correlates of humanized perception in moral decision making.

PubMed

Majdandžić, Jasminka; Bauer, Herbert; Windischberger, Christian; Moser, Ewald; Engl, Elisabeth; Lamm, Claus

2012-01-01

The extent to which people regard others as full-blown individuals with mental states ("humanization") seems crucial for their prosocial motivation towards them. Previous research has shown that decisions about moral dilemmas in which one person can be sacrificed to save multiple others do not consistently follow utilitarian principles. We hypothesized that this behavior can be explained by the potential victim's perceived humanness and an ensuing increase in vicarious emotions and emotional conflict during decision making. Using fMRI, we assessed neural activity underlying moral decisions that affected fictitious persons that had or had not been experimentally humanized. In implicit priming trials, participants either engaged in mentalizing about these persons (Humanized condition) or not (Neutral condition). In subsequent moral dilemmas, participants had to decide about sacrificing these persons' lives in order to save the lives of numerous others. Humanized persons were sacrificed less often, and the activation pattern during decisions about them indicated increased negative affect, emotional conflict, vicarious emotions, and behavioral control (pgACC/mOFC, anterior insula/IFG, aMCC and precuneus/PCC). Besides, we found enhanced effective connectivity between aMCC and anterior insula, which suggests increased emotion regulation during decisions affecting humanized victims. These findings highlight the importance of others' perceived humanness for prosocial behavior - with aversive affect and other-related concern when imagining harming more "human-like" persons acting against purely utilitarian decisions.

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.

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…

Local vs. volume conductance activity of field potentials in the human subthalamic nucleus

PubMed Central

Marmor, Odeya; Valsky, Dan; Joshua, Mati; Bick, Atira S; Arkadir, David; Tamir, Idit; Bergman, Hagai; Israel, Zvi

2017-01-01

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300–9,000 Hz) and field potentials (3–100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson’s disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms. NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of

Need Satisfaction Moderates the Association Between Physical Activity and Affective States in Adults Aged 50+: an Activity-Triggered Ambulatory Assessment.

PubMed

Kanning, Martina; Hansen, Sylvia

2017-02-01

Substantial evidence shows that physical activities of daily living are positively correlated with affective states in middle-aged and older adults. However, people's physical activity decreases when they grow older, and conditions that enhance older individuals' physical activities of daily living are not well understood. This study investigated need satisfaction (competence, relatedness, and autonomy) and its moderating effect on the within-subject relation between physical activities of daily living and three dimensions of affective states (valence, energetic arousal, and calmness) based on an ambulatory assessment that used activity-triggered e-diaries. The physical activities of daily living of 68 adults aged 50+ (mean age = 60.1 ± 7.1) were measured objectively for three consecutive days, and need satisfaction and affective states were assessed as a function of the amount of physical activity during the preceding 10 min before the affect measurement (in activity-triggered e-diaries). Hierarchical multilevel analyses were performed. Need satisfaction was significantly and positively correlated with the three dimensions of affective states. Further, physical activities of daily living were significantly associated with energetic arousal and calmness, but not valence. However, when physical activities of daily living were more autonomously regulated, the association of physical activities of daily living and valence became significant and positive. The findings regarding the significant moderating effects of need satisfaction are crucial for interventions aiming to improve the health-enhancing effects of physical activity in adults aged 50+. Positive feelings owing to physical activities in daily living depend on the extent that psychological needs are satisfied.

In vitro effect of important herbal active constituents on human cytochrome P450 1A2 (CYP1A2) activity.

PubMed

Pan, Yan; Tiong, Kai Hung; Abd-Rashid, Badrul Amini; Ismail, Zakiah; Ismail, Rusli; Mak, Joon Wah; Ong, Chin Eng

2014-10-15

This study was designed to investigate eight herbal active constituents (andrographolide, asiaticoside, asiatic acid, madecassic acid, eupatorin, sinensetin, caffeic acid, and rosmarinic acid) on their potential inhibitory effects on human cytochrome P450 1A2 (CYP1A2) activity. A fluorescence-based enzyme assay was performed by co-incubating human cDNA-expressed CYP1A2 with its selective probe substrate, 3-cyano-7-ethoxycoumarin (CEC), in the absence or presence of various concentrations of herbal active constituents. The metabolite (cyano-hydroxycoumarin) formed was subsequently measured in order to obtain IC50 values. The results indicated that only eupatorin and sinensetin moderately inhibited CYP1A2 with IC50 values of 50.8 and 40.2 μM, while the other active compounds did not significantly affect CYP1A2 activity with IC50 values more than 100 μM. Ki values further determined for eupatorin and sinensetin were 46.4 and 35.2 μM, respectively. Our data indicated that most of the investigated herbal constituents have negligible CYP1A2 inhibitory effect. In vivo studies however may be warranted to ascertain the inhibitory effect of eupatorin and sinensetin on CYP1A2 activity in clinical situations. Copyright © 2014 Elsevier GmbH. All rights reserved.

Crude and purified proteasome activity assays are affected by type of microplate.

PubMed

Cui, Ziyou; Gilda, Jennifer E; Gomes, Aldrin V

2014-02-01

Measurement of proteasome activity is fast becoming a commonly used assay in many laboratories. The most common method to measure proteasome activity involves measuring the release of fluorescent tags from peptide substrates in black microplates. Comparisons of black plates used for measuring fluorescence with different properties show that the microplate properties significantly affect the measured activities of the proteasome. The microplate that gave the highest reading of trypsin-like activity of the purified 20S proteasome gave the lowest reading of chymotrypsin-like activity of the 20S proteasome. Plates with medium binding surfaces from two different companies showed an approximately 2-fold difference in caspase-like activity for purified 20S proteasomes. Even standard curves generated using free 7-amino-4-methylcoumarin (AMC) were affected by the microplate used. As such, significantly different proteasome activities, as measured in nmol AMC released/mg/min, were obtained for purified 20S proteasomes as well as crude heart and liver samples when using different microplates. The naturally occurring molecule betulinic acid activated the chymotrypsin-like proteasome activity in three different plates but did not affect the proteasome activity in the nonbinding surface microplate. These findings suggest that the type of proteasome activity being measured and sample type are important when selecting a microplate. Copyright © 2013 Elsevier Inc. All rights reserved.

A Mechanistic Model of Human Recall of Social Network Structure and Relationship Affect.

PubMed

Omodei, Elisa; Brashears, Matthew E; Arenas, Alex

2017-12-07

The social brain hypothesis argues that the need to deal with social challenges was key to our evolution of high intelligence. Research with non-human primates as well as experimental and fMRI studies in humans produce results consistent with this claim, leading to an estimate that human primary groups should consist of roughly 150 individuals. Gaps between this prediction and empirical observations can be partially accounted for using "compression heuristics", or schemata that simplify the encoding and recall of social information. However, little is known about the specific algorithmic processes used by humans to store and recall social information. We describe a mechanistic model of human network recall and demonstrate its sufficiency for capturing human recall behavior observed in experimental contexts. We find that human recall is predicated on accurate recall of a small number of high degree network nodes and the application of heuristics for both structural and affective information. This provides new insight into human memory, social network evolution, and demonstrates a novel approach to uncovering human cognitive operations.

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity

PubMed Central

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; da Mota, Glória de Fátima Alves; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Introduction: Previous studies have linked angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. Materials and methods: A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O2 consumption (VO2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two-way repeated-measures ANOVA were used. Results: In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N

[Factors affecting maternal physical activities: an analysis based on the structural equation modeling].

PubMed

Liu, Yi; Luo, Bi-Ru

2016-11-20

To analyze the factors affecting maternal physical activities at different stages among pregnant women. Self-designed questionnaires were used to investigate the physical activities of women in different stages, including 650 in the first, 650 in the second, and 750 in the third trimester of pregnancy. The factors affecting maternal physical activities were analyzed using the structural equation model that comprised 4 latent variables (attitude, norm, behavioral attention and behavior) with observed variables that matched the latent variables. The participants ranged from 18 to 35 years of age. The women and their husbands, but not their mothers or mothers-in-law, were all well educated. The caregiver during pregnancy was mostly the mother followed by the husband. For traveling, the women in the first, second and third trimesters preferred walking, bus, and personal escort, respectively; the main physical activity was walking in all trimesters, and the women in different trimester were mostly sedentary, a greater intensity of exercise was associated with less exercise time. Structural equation modeling (SEM) analysis showed that the physical activities of pregnant women was affected by behavioral intention (with standardized regression coefficient of 0.372); attitude and subjective norms affected physical activity by indirectly influencing the behavior intention (standardized regression coefficients of 0.140 and 0.669). The pregnant women in different stages have inappropriate physical activities with insufficient exercise time and intensity. The subjective norms affects the physical activities of the pregnant women by influencing their attitudes and behavior intention indirectly, suggesting the need of health education of the caregivers during pregnancy.

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.

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

Abnormal activity in reward brain circuits in human narcolepsy with cataplexy.

PubMed

Ponz, Aurélie; Khatami, Ramin; Poryazova, Rositsa; Werth, Esther; Boesiger, Peter; Bassetti, Claudio L; Schwartz, Sophie

2010-02-01

Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients.

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.

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

A Meta-Analysis of Factors Affecting Trust in Human-Robot Interaction

DTIC Science & Technology

2011-10-01

directly affects the willingness of people to accept robot -produced information, follow robots ’ suggestions, and thus benefit from the advantages inherent...perceived complexity of operation). Consequently, if the perceived risk of using the robot exceeds its perceived benefit , practical operators almost...necessary presence of a human caregiver (Graf, Hans, & Schraft, 2004). Other robotic devices, such as wheelchairs (Yanco, 2001) and exoskeletons (e.g

Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity.

PubMed

Kuchiike, Daisuke; Uto, Yoshihiro; Mukai, Hirotaka; Ishiyama, Noriko; Abe, Chiaki; Tanaka, Daichi; Kawai, Tomohito; Kubo, Kentaro; Mette, Martin; Inui, Toshio; Endo, Yoshio; Hori, Hitoshi

2013-07-01

The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.

Perfluoroalkylated substances (PFAS) affect neither estrogen and androgen receptor activity nor steroidogenesis in human cells in vitro.

PubMed

Behr, Anne-Cathrin; Lichtenstein, Dajana; Braeuning, Albert; Lampen, Alfonso; Buhrke, Thorsten

2018-07-01

The perfluoroalkylated substances (PFAS) perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are used for the fabrication of water- and dirt-repellent surfaces. The use of PFOS and PFOA was restricted due to their reprotoxic properties and their environmental persistence. Therefore, industry switches to alternative PFAS, however, in contrast to PFOA and PFOS only few toxicological data are available for their substitutes. The molecular mechanism(s) underlying reproductive toxicity of PFOA and PFOS are largely unknown. Here, the endocrine properties of PFOA, PFOS, and of six substitutes including perfluorohexanesulfonic acid (PFHxS), perfluorobutanesulfonic acid (PFBS), perfluorohexanoic acid (PFHxA), perfluorobutanoic acid (PFBA), ammonium perfluoro(2-methyl-3-oxahexanoate) (PMOH), and 3H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP) were examined in vitro by using human cell lines such as MCF-7, H295R, LNCaP and MDA-kb2. PFOA, PFOS and PMOH enhanced 17β-estradiol-stimulated estrogen receptor β activity, and PFOS, PMOH, PFHxA and PFBA enhanced dihydrotestosterone-stimulated androgen receptor activity. In the H295R steroidogenesis assay, PFOA and PFOS slightly enhanced estrone secretion, and progesterone secretion was marginally increased by PFOA. All these effects were only observed at concentrations above 10 μM, and none of the PFAS displayed any effect on any of the molecular endocrine endpoints at concentrations of 10 μM or below. Thus, as the blood serum concentrations of the different PFAS in the general Western population are in the range of 10 nM or below, the results suggest that PFAS might not exert endocrine effects in humans at exposure-relevant concentrations according to the molecular endpoints examined in this study. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of activity in human dynamics

NASA Astrophysics Data System (ADS)

Zhou, T.; Kiet, H. A. T.; Kim, B. J.; Wang, B.-H.; Holme, P.

2008-04-01

The human society is a very complex system; still, there are several non-trivial, general features. One type of them is the presence of power-law-distributed quantities in temporal statistics. In this letter, we focus on the origin of power laws in rating of movies. We present a systematic empirical exploration of the time between two consecutive ratings of movies (the interevent time). At an aggregate level, we find a monotonous relation between the activity of individuals and the power law exponent of the interevent time distribution. At an individual level, we observe a heavy-tailed distribution for each user, as well as a negative correlation between the activity and the width of the distribution. We support these findings by a similar data set from mobile phone text-message communication. Our results demonstrate a significant role of the activity of individuals on the society-level patterns of human behavior. We believe this is a common character in the interest-driven human dynamics, corresponding to (but different from) the universality classes of task-driven dynamics.

Pyoverdine and Proteases Affect the Response of Pseudomonas aeruginosa to Gallium in Human Serum

PubMed Central

Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco

2015-01-01

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. PMID:26149986

75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-19

...: Notice. Notice of Intent to increase funding available to make awards under the Centers for Disease Control and Prevention Funding Opportunity Announcement CDC-RFA-PS10-10138, ``Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations''. Additional funding from the...

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

Distributed Neural Activity Patterns during Human-to-Human Competition

PubMed Central

Piva, Matthew; Zhang, Xian; Noah, J. Adam; Chang, Steve W. C.; Hirsch, Joy

2017-01-01

Interpersonal interaction is the essence of human social behavior. However, conventional neuroimaging techniques have tended to focus on social cognition in single individuals rather than on dyads or groups. As a result, relatively little is understood about the neural events that underlie face-to-face interaction. We resolved some of the technical obstacles inherent in studying interaction using a novel imaging modality and aimed to identify neural mechanisms engaged both within and across brains in an ecologically valid instance of interpersonal competition. Functional near-infrared spectroscopy was utilized to simultaneously measure hemodynamic signals representing neural activity in pairs of subjects playing poker against each other (human–human condition) or against computer opponents (human–computer condition). Previous fMRI findings concerning single subjects confirm that neural areas recruited during social cognition paradigms are individually sensitive to human–human and human–computer conditions. However, it is not known whether face-to-face interactions between opponents can extend these findings. We hypothesize distributed effects due to live processing and specific variations in across-brain coherence not observable in single-subject paradigms. Angular gyrus (AG), a component of the temporal-parietal junction (TPJ) previously found to be sensitive to socially relevant cues, was selected as a seed to measure within-brain functional connectivity. Increased connectivity was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as well as a complex including the left subcentral area (SCA) and somatosensory cortex (SS) during interaction with a human opponent. These distributed findings were supported by contrast measures that indicated increased activity at the left dlPFC and frontopolar area that partially overlapped with the region showing increased functional connectivity with AG. Across-brain analyses of neural coherence

Deficient erythrocyte NaK-ATPase activity in different affective states in bipolar affective disorder and normalization by lithium therapy.

PubMed

Hokin-Neaverson, M; Jefferson, J W

1989-01-01

This report expands on previously presented evidence for a trait-dependent deficiency of erythrocyte sodium pump activity in bipolar affective disorder. Several parameters of erythrocyte NaK-ATPase activity in different affective states and the effects of lithium therapy were examined. In lithium-free bipolar affective disorder patients, the mean percent differences from the individual sex- and age-matched controls for erythrocyte sodium pump activity were: manic + hypomanic group, -21.5%, n = 16, p less than 0.02; depressed group, -12.4%, n = 14, p less than 0.02; euthymic group, -6.9%, n = 18, p less than 0.10. Ouabain-sensitive potassium ion uptake was less than the controls in the manic group (-25.4%, n = 3, p less than 0.02), and in the combined affectively ill group, manic + depressed (-23.4%, n = 7, p less than 0.02). Cell ouabain binding was less than the controls in the manic group (-19.0%, n = 6, p less than 0.05). NaK-ATPase activity in washed erythrocyte membranes (ghosts) was significantly lower than the controls in the manic group (-14.5%, n = 4, p less than 0.02), and the mean value for the whole group (manic + depressed + euthymic) was lower than the controls (-11.8%, n = 18, p less than 0.05). Values for ouabain binding in ghosts from the bipolar subjects were not significantly different from the matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice.

PubMed

Kido, Tatsuo; Sun, Zhaoyu; Lau, Yun-Fai Chris

2017-06-23

Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRY ON ) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRY ON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.

Oleuropein potentiates anti-tumor activity of cisplatin against HepG2 through affecting proNGF/NGF balance.

PubMed

Sherif, Iman O; Al-Gayyar, Mohammed M H

2018-04-01

Oleuropein is considered as a new chemotherapeutic agent in human hepatocellular carcinoma (HCC) while, its exact underlying molecular mechanism still not yet explored. In addition, cisplatin is a standard anticancer drug against solid tumors with toxic side effects. Therefore, we conducted this study to assess antitumor activity of oleuropein either alone or in combination with cisplatin against HepG2, human HCC cell lines, via targeting pro-NGF/NGF signaling pathway. HepG2 cells were treated with cisplatin (20, 50, 100 μM) and oleuropein (100, 200, 300 and 400 μM) as well as some of the cells were treated with 50 μM cisplatin and different concentrations of oleuropein. Gene expressions of nerve growth factor (NGF), matrix metalloproteinase-7 (MMP-7) and caspase-3 were evaluated by real time-PCR. In addition, protein levels of NGF and pro-form of NGF (pro-NGF) were measured by ELISA while, nitric oxide (NO) content was determined colorimetrically. Cisplatin treatment showed a significant elevation of NO content and pro-NGF protein level with a marked reduction of NGF protein level in addition to the upregulation of caspase-3 along with downregulation of MMP-7 gene expressions in a dose-dependent manner. However, the combination of 50 μM cisplatin and 200 μM oleuropein showed the most potent effect on the molecular level when compared with oleuropein or cisplatin alone. Our results showed for the first time that the anti-tumor activity of oleuropein against HCC could be attributed to influencing the pro-NGF/NGF balance via affecting MMP-7 activity without affecting the gene expression of NGF. Concurrent treatment with both oleuropein and cisplatin could lead to more effective chemotherapeutic combination against HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human.

PubMed

Wu, Yu-Jing; Chen, Heng-Shi; Chen, Wen-Sheng; Dong, Jin; Dong, Xiao-Jie; Dai, Xing; Huang, Qiong; Wei, Wei

2018-01-01

Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6'- O -benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4 + T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4 + T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4 + T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr 394 ). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4 + T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr 394 ) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4 + T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

Cytochrome P450 Activity in Ex Vivo Cornea Models and a Human Cornea Construct.

PubMed

Kölln, Christian; Reichl, Stephan

2016-07-01

The pharmacokinetic behaviors of novel ophthalmic drugs are often preliminarily investigated in preclinical studies using ex vivo animal cornea or corneal cell culture models. During transcorneal passage, topically applied drugs may be affected by drug metabolizing enzymes. The knowledge regarding the functional expression of metabolic enzymes in corneal tissue is marginal; thus, the aim of this study was to investigate cytochrome P450 activity in an organotypic three-dimensional human cornea construct and to compare it with porcine and rabbit corneas, which are commonly used ex vivo cornea models. The total cytochrome P450 activity was determined by measuring the transformation of 7-ethoxycoumarin. Furthermore, the expression of the cytochrome P450 enzyme 2D6 (CYP2D6) was investigated at the protein level using immunohistochemistry and western blotting. CYP2D6 activity measurements were performed using a d-luciferin-based assay. In summary, similar levels of the total cytochrome P450 activity were identified in all 3 cornea models. The protein expression of CYP2D6 was confirmed in the human cornea construct and porcine cornea, whereas the signals in the rabbit cornea were weak. The analysis of the CYP2D6 activity indicated similar values for the human cornea construct and porcine cornea; however, a distinctly lower activity was observed in the rabbit cornea. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Complex Human Activity Recognition Using Smartphone and Wrist-Worn Motion Sensors.

PubMed

Shoaib, Muhammad; Bosch, Stephan; Incel, Ozlem Durmaz; Scholten, Hans; Havinga, Paul J M

2016-03-24

The position of on-body motion sensors plays an important role in human activity recognition. Most often, mobile phone sensors at the trouser pocket or an equivalent position are used for this purpose. However, this position is not suitable for recognizing activities that involve hand gestures, such as smoking, eating, drinking coffee and giving a talk. To recognize such activities, wrist-worn motion sensors are used. However, these two positions are mainly used in isolation. To use richer context information, we evaluate three motion sensors (accelerometer, gyroscope and linear acceleration sensor) at both wrist and pocket positions. Using three classifiers, we show that the combination of these two positions outperforms the wrist position alone, mainly at smaller segmentation windows. Another problem is that less-repetitive activities, such as smoking, eating, giving a talk and drinking coffee, cannot be recognized easily at smaller segmentation windows unlike repetitive activities, like walking, jogging and biking. For this purpose, we evaluate the effect of seven window sizes (2-30 s) on thirteen activities and show how increasing window size affects these various activities in different ways. We also propose various optimizations to further improve the recognition of these activities. For reproducibility, we make our dataset publicly available.

Complex Human Activity Recognition Using Smartphone and Wrist-Worn Motion Sensors

PubMed Central

Shoaib, Muhammad; Bosch, Stephan; Incel, Ozlem Durmaz; Scholten, Hans; Havinga, Paul J. M.

2016-01-01

The position of on-body motion sensors plays an important role in human activity recognition. Most often, mobile phone sensors at the trouser pocket or an equivalent position are used for this purpose. However, this position is not suitable for recognizing activities that involve hand gestures, such as smoking, eating, drinking coffee and giving a talk. To recognize such activities, wrist-worn motion sensors are used. However, these two positions are mainly used in isolation. To use richer context information, we evaluate three motion sensors (accelerometer, gyroscope and linear acceleration sensor) at both wrist and pocket positions. Using three classifiers, we show that the combination of these two positions outperforms the wrist position alone, mainly at smaller segmentation windows. Another problem is that less-repetitive activities, such as smoking, eating, giving a talk and drinking coffee, cannot be recognized easily at smaller segmentation windows unlike repetitive activities, like walking, jogging and biking. For this purpose, we evaluate the effect of seven window sizes (2–30 s) on thirteen activities and show how increasing window size affects these various activities in different ways. We also propose various optimizations to further improve the recognition of these activities. For reproducibility, we make our dataset publicly available. PMID:27023543

Activation of human T cells in hypertension: Studies of Humanized Mice and Hypertensive Humans

PubMed Central

Itani, Hana A.; McMaster, William G.; Saleh, Mohamed A.; Nazarewicz, Rafal R.; Mikolajczyk, Tomasz P.; Kaszuba, Anna; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E.; Chen, Wei; Bonami, Rachel H.; Marshall, Andrew F.; Poffenberger, Greg; Weyand, Cornelia M.; Madhur, Meena S.; Moore, Daniel J.; Harrison, David G.; Guzik, Tomasz J.

2016-01-01

Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We employed a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 mm Hg vs. 116 mm Hg for sham treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta and kidney revealed increased infiltration of human leukocytes (CD45+) and T lymphocytes (CD3+ and CD4+) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3+/CD45RO+) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T cell proliferation. We also observed an increase in circulating IL-17A producing CD4+ T cells and both CD4+ and CD8+ T cells that produce IFN-γ in hypertensive compared to normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II. PMID:27217403

Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans.

PubMed

Itani, Hana A; McMaster, William G; Saleh, Mohamed A; Nazarewicz, Rafal R; Mikolajczyk, Tomasz P; Kaszuba, Anna M; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E; Chen, Wei; Bonami, Rachel H; Marshall, Andrew F; Poffenberger, Greg; Weyand, Cornelia M; Madhur, Meena S; Moore, Daniel J; Harrison, David G; Guzik, Tomasz J

2016-07-01

Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We used a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 versus 116 mm Hg for sham-treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta, and kidney revealed increased infiltration of human leukocytes (CD45(+)) and T lymphocytes (CD3(+) and CD4(+)) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3(+)/CD45RO(+)) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T-cell proliferation. We also observed an increase in circulating interleukin-17A producing CD4(+) T cells and both CD4(+) and CD8(+) T cells that produce interferon-γ in hypertensive compared with normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II. © 2016 American Heart Association, Inc.

Interpretation of Statistical Data: The Importance of Affective Expressions

ERIC Educational Resources Information Center

Queiroz, Tamires; Monteiro, Carlos; Carvalho, Liliane; François, Karen

2017-01-01

In recent years, research on teaching and learning of statistics emphasized that the interpretation of data is a complex process that involves cognitive and technical aspects. However, it is a human activity that involves also contextual and affective aspects. This view is in line with research on affectivity and cognition. While the affective…

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

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

PubMed Central

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

2012-01-01

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

Vegetation dynamics and responses to climate change and human activities in Central Asia.

PubMed

Jiang, Liangliang; Guli Jiapaer; Bao, Anming; Guo, Hao; Ndayisaba, Felix

2017-12-01

Knowledge of the current changes and dynamics of different types of vegetation in relation to climatic changes and anthropogenic activities is critical for developing adaptation strategies to address the challenges posed by climate change and human activities for ecosystems. Based on a regression analysis and the Hurst exponent index method, this research investigated the spatial and temporal characteristics and relationships between vegetation greenness and climatic factors in Central Asia using the Normalized Difference Vegetation Index (NDVI) and gridded high-resolution station (land) data for the period 1984-2013. Further analysis distinguished between the effects of climatic change and those of human activities on vegetation dynamics by means of a residual analysis trend method. The results show that vegetation pixels significantly decreased for shrubs and sparse vegetation compared with those for the other vegetation types and that the degradation of sparse vegetation was more serious in the Karakum and Kyzylkum Deserts, the Ustyurt Plateau and the wetland delta of the Large Aral Sea than in other regions. The Hurst exponent results indicated that forests are more sustainable than grasslands, shrubs and sparse vegetation. Precipitation is the main factor affecting vegetation growth in the Kazakhskiy Melkosopochnik. Moreover, temperature is a controlling factor that influences the seasonal variation of vegetation greenness in the mountains and the Aral Sea basin. Drought is the main factor affecting vegetation degradation as a result of both increased temperature and decreased precipitation in the Kyzylkum Desert and the northern Ustyurt Plateau. The residual analysis highlighted that sparse vegetation and the degradation of some shrubs in the southern part of the Karakum Desert, the southern Ustyurt Plateau and the wetland delta of the Large Aral Sea were mainly triggered by human activities: the excessive exploitation of water resources in the upstream areas

Subliminal words durably affect neuronal activity.

PubMed

Gaillard, Raphaël; Cohen, Laurent; Adam, Claude; Clemenceau, Stéphane; Hasboun, Dominique; Baulac, Michel; Willer, Jean-Claude; Dehaene, Stanislas; Naccache, Lionel

2007-10-08

Unconscious mental representations elicited by subliminal stimuli are marked by their fleeting lifetimes, usually below 1 s. Can such evanescent subliminal stimuli, nevertheless, lead to long-lasting learning? To date, evidence suggesting a long-term influence of briefly perceived stimuli on behaviour or brain activity is scarce and questionable. In this study, we used intracranial recordings to provide the first direct demonstration that unconsciously perceived subliminal words could exert long-lasting effects on neuronal signals. When repeating subliminal words over long interstimulus intervals, we observed electrophysiological repetition effects. These unconscious repetition effects suggest that the single presentation of a masked word can durably affect neural architecture.

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.

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

48 CFR 3452.224-72 - Research activities involving human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011) (a...

Multilevel depth and image fusion for human activity detection.

PubMed

Ni, Bingbing; Pei, Yong; Moulin, Pierre; Yan, Shuicheng

2013-10-01

Recognizing complex human activities usually requires the detection and modeling of individual visual features and the interactions between them. Current methods only rely on the visual features extracted from 2-D images, and therefore often lead to unreliable salient visual feature detection and inaccurate modeling of the interaction context between individual features. In this paper, we show that these problems can be addressed by combining data from a conventional camera and a depth sensor (e.g., Microsoft Kinect). We propose a novel complex activity recognition and localization framework that effectively fuses information from both grayscale and depth image channels at multiple levels of the video processing pipeline. In the individual visual feature detection level, depth-based filters are applied to the detected human/object rectangles to remove false detections. In the next level of interaction modeling, 3-D spatial and temporal contexts among human subjects or objects are extracted by integrating information from both grayscale and depth images. Depth information is also utilized to distinguish different types of indoor scenes. Finally, a latent structural model is developed to integrate the information from multiple levels of video processing for an activity detection. Extensive experiments on two activity recognition benchmarks (one with depth information) and a challenging grayscale + depth human activity database that contains complex interactions between human-human, human-object, and human-surroundings demonstrate the effectiveness of the proposed multilevel grayscale + depth fusion scheme. Higher recognition and localization accuracies are obtained relative to the previous methods.

Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-alpha receptor levels in humans with relative leptin deficiency.

PubMed

Chan, Jean L; Moschos, Stergios J; Bullen, John; Heist, Kathleen; Li, Xian; Kim, Young-Bum; Kahn, Barbara B; Mantzoros, Christos S

2005-03-01

Studies of congenital complete leptin deficiency in animals and humans support a role for leptin in regulating immune function. Whether acquired relative leptin deficiency affects immunological parameters in healthy humans remains unknown. We thus used experimental models of relative leptin deficiency and recombinant methionyl human leptin (r-metHuLeptin) administration in humans to investigate whether r-metHuLeptin would activate signaling pathways in peripheral blood mononuclear cells (PBMCs) and whether acquired relative leptin deficiency and/or increasing circulating leptin levels into the physiologic range would change PBMC subpopulations and cytokines important in the T-helper cell and systemic immune responses. We found that r-metHuLeptin administration to healthy humans activates signal transducer and activator of transcription-3 signaling in PBMCs in vivo. Neither short-term leptin deficiency, induced by 3-d complete fasting, nor physiologic r-metHuLeptin replacement for the same period of time had a major effect on PBMC subpopulations or serum cytokines in healthy men. In contrast, normalizing serum leptin levels over 8 wk in lean women with relative leptin deficiency for 5.1 +/- 1.4 yr (mean +/- se) due to chronic energy deficit increased soluble TNFalpha receptor levels, indicating activation of the TNFalpha system. These findings suggest that relative leptin deficiency due to more long-term energy deprivation is associated with defects in immunological parameters that may be corrected with exogenous r-metHuLeptin administration. Further studies are warranted to assess the implications of acquired relative hypoleptinemia and/or r-metHuLeptin administration on the immunosuppression associated with energy- and leptin-deficient states in humans.

A time-lagged momentary assessment study on daily life physical activity and affect.

PubMed

Wichers, Marieke; Peeters, Frenk; Rutten, Bart P F; Jacobs, Nele; Derom, Catherine; Thiery, Evert; Delespaul, Philippe; van Os, Jim

2012-03-01

Novel study designs using within-subject methodology and frequent and prospective measurements are required to unravel direction of causality and dynamic processes of behavior over time. The current study examined the effects of physical activity on affective state. A primary and within-study replication sample was derived from twin pairs. Female twins (n = 504) participated in an experience sampling method study at baseline. Positive and negative affective changes were examined before and following daily life increases in physical activity. Neuroticism was measured at baseline and depressive symptoms were assessed at baseline and at each of four follow-up assessments. Diagnoses, derived by Structured Clinical Interview for Diagnostic and Statistical Manual for Mental Health-IV axis I disorders, (A. P. A., 1994) were obtained at baseline. A significant increase in positive affect (PA) following the moment of increase in physical activity was replicated across both samples up to 180 min after physical activity. There was no effect of physical activity on negative affect (NA). Across the two samples, a history of fulfilling diagnostic criteria for depression at least once moderated the effect of physical activity on PA, in that the effect was lost more rapidly. The study supports a causal effect of physical activity on PA. However, people with past experience of clinical depression may benefit less from the PA-inducing effect of physical activity. These findings have implications for the use of physical exercise in clinical practice.

Human activities change marine ecosystems by altering predation risk.

PubMed

Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

2016-01-01

In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. © 2015 John Wiley & Sons Ltd.

Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARα) by perfluoroalkyl acids (PFAAs) of 5, 7, 8, 11, and 12 carbon chain lengths in C05-1 cells.

EPA Science Inventory

PFAAs are surfactants that have been found globally in the environment and in tissues of humans and wildlife. They adversely affect perinatal survival and development in rodents and PPARα is involved in inducing these effects. Our previous study demonstrated that some PFAAs activ...

Involvement of Sp1 elements in the promoter activity of genes affected in keratoconus.

PubMed

Maruyama, Y; Wang, X; Li, Y; Sugar, J; Yue, B Y

2001-08-01

Keratoconus is a progressive disease that thins and scars the corneal stroma. In keratoconus corneas, levels of degradative enzymes, including lysosomal acid phosphatase (LAP) and cathepsin B, are elevated, and those of the inhibitors alpha1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M) are reduced, especially in the epithelial layer. An increased expression of the transcription factor Sp1 was also demonstrated. The role of Sp1 in regulation of the genes affected in keratoconus was examined in this study. DNA segments, containing 5'-flanking promoter sequences of the alpha 1-PI, LAP, cathepsin B, and alpha 2-M genes were ligated into the secreted alkaline phosphatase (SEAP) reporter gene vector. These constructs, along with the pSV beta-galactosidase control vector, were transfected into cultured human corneal epithelial and stromal cells and skin fibroblasts. Cotransfection with the Sp1 expression vector was performed in parallel. SEAP and beta-galactosidase enzyme activities were assayed. In corneal epithelial cells, as in stromal cells, alpha 1-PI promoter activity was suppressed by cotransfection of pPacSp1. The LAP, cathepsin B, and alpha 2-M promoters were functional in corneal cells, whereas activities of these promoters were much lower in skin fibroblasts. Cotransfection experiments indicated that the up- or downregulation of LAP, cathepsin B, and alpha 2-M observed in keratoconus-affected corneas was not mediated by Sp1. These results support the theory that the corneal epithelium, along with the stroma, is involved in keratoconus. An upstream role of Sp1 is indicated and the Sp1-mediated downregulation of the alpha 1-PI gene may be a key event in the disease development.

Anxiety affects the amplitudes of red and green color-elicited flash visual evoked potentials in humans.

PubMed

Hosono, Yuki; Kitaoka, Kazuyoshi; Urushihara, Ryo; Séi, Hiroyoshi; Kinouchi, Yohsuke

2014-01-01

It has been reported that negative emotional changes and conditions affect the visual faculties of humans at the neural level. On the other hand, the effects of emotion on color perception in particular, which are based on evoked potentials, are unknown. In the present study, we investigated whether different anxiety levels affect the color information processing for each of 3 wavelengths by using flash visual evoked potentials (FVEPs) and State-Trait Anxiety Inventory. In results, significant positive correlations were observed between FVEP amplitudes and state or trait anxiety scores in the long (sensed as red) and middle (sensed as green) wavelengths. On the other hand, short-wavelength-evoked FVEPs were not correlated with anxiety level. Our results suggest that negative emotional conditions may affect color sense processing in humans.

2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation.

PubMed

Lee, Yi-Nan; Yeh, Hung-I; Tian, Tin-Yi; Lu, Wen-Wei; Ko, Yu-Shien; Tsai, Cheng-Ho

2002-09-30

We examined the effect of 2',5'-dihydroxychalcone on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2',5'-dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication function, determined by fluorescence recovery after photobleaching (FRAP), is decreased. We further investigated whether the mitogen-activated protein (MAP) kinase and the degradation pathway of gap junctions are involved in these processes. Although the change of Cx43 is not affected by the level of fetal calf serum (FCS) used in the medium, activation of MAP kinase varies, depending on the FCS level. At a low level (0.5%), the chalcone inhibits the activation, like PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level (20%), MAP kinase is activated. On the other hand, the chalcone's down-regulating effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N-acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We concluded that 2',5'-dihydroxychalcone down-regulates Cx43 expression and gap-junctional communication in the HUVEC via enhancement of the proteolysis pathway, and this compound possesses dual effects on MAP kinase activation.

Recognition of human activity characteristics based on state transitions modeling technique

NASA Astrophysics Data System (ADS)

Elangovan, Vinayak; Shirkhodaie, Amir

2012-06-01

Human Activity Discovery & Recognition (HADR) is a complex, diverse and challenging task but yet an active area of ongoing research in the Department of Defense. By detecting, tracking, and characterizing cohesive Human interactional activity patterns, potential threats can be identified which can significantly improve situation awareness, particularly, in Persistent Surveillance Systems (PSS). Understanding the nature of such dynamic activities, inevitably involves interpretation of a collection of spatiotemporally correlated activities with respect to a known context. In this paper, we present a State Transition model for recognizing the characteristics of human activities with a link to a prior contextbased ontology. Modeling the state transitions between successive evidential events determines the activities' temperament. The proposed state transition model poses six categories of state transitions including: Human state transitions of Object handling, Visibility, Entity-entity relation, Human Postures, Human Kinematics and Distance to Target. The proposed state transition model generates semantic annotations describing the human interactional activities via a technique called Casual Event State Inference (CESI). The proposed approach uses a low cost kinect depth camera for indoor and normal optical camera for outdoor monitoring activities. Experimental results are presented here to demonstrate the effectiveness and efficiency of the proposed technique.

The Human Factor: Behavioral and Neural Correlates of Humanized Perception in Moral Decision Making

PubMed Central

Majdandžić, Jasminka; Bauer, Herbert; Windischberger, Christian; Moser, Ewald; Engl, Elisabeth; Lamm, Claus

2012-01-01

The extent to which people regard others as full-blown individuals with mental states (“humanization”) seems crucial for their prosocial motivation towards them. Previous research has shown that decisions about moral dilemmas in which one person can be sacrificed to save multiple others do not consistently follow utilitarian principles. We hypothesized that this behavior can be explained by the potential victim’s perceived humanness and an ensuing increase in vicarious emotions and emotional conflict during decision making. Using fMRI, we assessed neural activity underlying moral decisions that affected fictitious persons that had or had not been experimentally humanized. In implicit priming trials, participants either engaged in mentalizing about these persons (Humanized condition) or not (Neutral condition). In subsequent moral dilemmas, participants had to decide about sacrificing these persons’ lives in order to save the lives of numerous others. Humanized persons were sacrificed less often, and the activation pattern during decisions about them indicated increased negative affect, emotional conflict, vicarious emotions, and behavioral control (pgACC/mOFC, anterior insula/IFG, aMCC and precuneus/PCC). Besides, we found enhanced effective connectivity between aMCC and anterior insula, which suggests increased emotion regulation during decisions affecting humanized victims. These findings highlight the importance of others’ perceived humanness for prosocial behavior - with aversive affect and other-related concern when imagining harming more “human-like” persons acting against purely utilitarian decisions. PMID:23082194

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.

Displacement activities as a behavioral measure of stress in nonhuman primates and human subjects.

PubMed

Troisi, Alfonso

2002-02-01

Traditionally, research on human stress has relied mostly on physiological and psychological measures with a relatively minor emphasis on the behavioral aspects of the phenomenon. Such an approach makes it difficult to develop valid animal models of the human stress syndrome. A promising approach to the study of the behavioral correlates of stress is to analyze those behavior patterns that ethologists have named displacement activities and that, in primates, consist mostly of self-directed behaviors. In both nonhuman primates and human subjects, displacement behavior appears in situations characterized by social tension and is likely to reflect increased autonomic arousal. Pharmacological studies of nonhuman primates have shown that the frequency of occurrence of displacement behavior is increased by anxiogenic compounds and decreased by anxiolytic drugs. Ethological studies of healthy persons and psychiatric patients during interviews have found that increased displacement behavior not only correlates with a subjective feeling state of anxiety and negative affect but also gives more veridical information about the subject's emotional state than verbal statements and facial expression. The measurement of displacement activities may be a useful complement to the physiological and psychological studies aimed at analyzing the correlates and consequences of stress.

Understanding human activity patterns based on space-time-semantics

NASA Astrophysics Data System (ADS)

Huang, Wei; Li, Songnian

2016-11-01

Understanding human activity patterns plays a key role in various applications in an urban environment, such as transportation planning and traffic forecasting, urban planning, public health and safety, and emergency response. Most existing studies in modeling human activity patterns mainly focus on spatiotemporal dimensions, which lacks consideration of underlying semantic context. In fact, what people do and discuss at some places, inferring what is happening at the places, cannot be simple neglected because it is the root of human mobility patterns. We believe that the geo-tagged semantic context, representing what individuals do and discuss at a place and a specific time, drives a formation of specific human activity pattern. In this paper, we aim to model human activity patterns not only based on space and time but also with consideration of associated semantics, and attempt to prove a hypothesis that similar mobility patterns may have different motivations. We develop a spatiotemporal-semantic model to quantitatively express human activity patterns based on topic models, leading to an analysis of space, time and semantics. A case study is conducted using Twitter data in Toronto based on our model. Through computing the similarities between users in terms of spatiotemporal pattern, semantic pattern and spatiotemporal-semantic pattern, we find that only a small number of users (2.72%) have very similar activity patterns, while the majority (87.14%) show different activity patterns (i.e., similar spatiotemporal patterns and different semantic patterns, similar semantic patterns and different spatiotemporal patterns, or different in both). The population of users that has very similar activity patterns is decreased by 56.41% after incorporating semantic information in the corresponding spatiotemporal patterns, which can quantitatively prove the hypothesis.

Melanocortin-1 receptor gene variants affect pain and µ-opioid analgesia in mice and humans

PubMed Central

Mogil, J; Ritchie, J; Smith, S; Strasburg, K; Kaplan, L; Wallace, M; Romberg, R; Bijl, H; Sarton, E; Fillingim, R; Dahan, A

2005-01-01

Background: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on κ-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant µ-opioid receptor. Objective: To characterise sensitivity to pain and µ-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. Methods: Comparisons of spontaneous mutant C57BL/6-Mc1re/e mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. Results: C57BL/6-Mc1re/e mutant mice and human redheads—both with non-functional MC1Rs—display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the µ-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. Conclusions: Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics. PMID:15994880

Effect of viscous fiber (guar) on postprandial motor activity in human small bowel.

PubMed

Schönfeld, J; Evans, D F; Wingate, D L

1997-08-01

Both caloric value and chemical composition of a meal have been shown to regulate postprandial small bowel motility in dog. In the same species, duration of and contractile activity within the postprandial period also depends on mean viscosity. It is unknown, however, whether meal viscosity and fiber content also regulate small bowel motor activity in man. In human volunteers, we therefore studied the effect of guar gum on small bowel motor response to liquid and solid meals. Twenty-six prolonged ambulatory small bowel manometry studies were performed in 12 volunteers. A total of 620 hr of recording were analyzed visually for phase III of the MMC and a validated computer program calculated the incidence and amplitude of contractions after ingestion of water (300 ml), a pure glucose drink (300 ml/330 kcal) or a solid meal (530 kcal) with and without 5 g of guar gum. Addition of 5 g of guar gum did not significantly delay reappearance of phase III after ingestion of water (59 +/- 11 vs 106 +/- 21 min; P = 0.09). However, guar gum significantly prolonged duration of postprandial motility pattern both after the glucose drink (123 +/- 19 vs 199 +/- 24 min; P < 0.05) and after the solid meal (310 +/- 92 vs 419 +/- 22 min; P = 0.005). Contractile activity during these periods was not affected by guar gum. This was true for mean incidence of contractions after water (1.9 +/- 0.3 vs 1.8 +/- 0.5 min-1), after the glucose drink (1.6 +/- 0.4 vs. 1.7 +/- 0.3 min-1) and after the solid meal (2.4 +/- 0.4 vs 2.6 +/- 0.4 min-1). Likewise, mean amplitude of contractions was not affected by guar gum after water (22.8 +/- 1.4 vs 20.9 +/- 1.9 mm Hg), after the glucose drink (20.5 +/- 1.4 vs 21.3 +/- 1.2), and after the solid meal (20.3 +/- 1.5 vs 21.5 +/- 1.6 mm Hg). Thus a guar gum-induced increase in chyme viscosity markedly prolonged duration of postprandial motor activity in the human small bowel. Contractile activity within the postprandial period, however, was not affected. We

New activity pattern in human interactive dynamics

NASA Astrophysics Data System (ADS)

Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni

2015-09-01

We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Interleukin-3 Does Not Affect the Differentiation of Mast Cells Derived from Human Bone Marrow Progenitors

PubMed Central

Shimizu, Yuji; Matsumoto, Kenji; Okayama, Yoshimichi; Kentaro, Sakai; Maeno, Toshitaka; Suga, Tatsuo; Miura, Toru; Takai, Shinji; Kurabayashi, Masahiko; Saito, Hirohisa

2008-01-01

Although IL-3 is commonly used for culture of human progenitor-derived mast cells together with Stem cell factor (SCF) and IL-6, the effect of IL-3 on human mast cell differentiation has not been well elucidated. Human bone marrow CD34+ progenitors were cultured for up to 12 weeks in the presence of rhSCF and rhIL-6 either with rhIL-3 (IL-3 (+)) or without rhIL-3 (IL-3 (−)) for the initial 1-week of culture. Total cell number increased at 2 weeks in IL-3 (+), as compared to IL-3 (−), but changes in the appearance of mast cells were delayed. When IL-3 was present for the initial 1-week culture, granules looked more mature with IL-3 than without IL-3. However, tryptase and chymase contents, and surface antigen expression (CD18, CD51, CD54, and CD117) were not altered by IL-3. Surface expression and mRNA level of FcεRIα and histamine release by crosslinking of FcεRIα did not differ from one preparation to the next. GeneChip analysis revealed that no significant differences were observed between IL-3 (+) and IL-3 (−) cells either when inactivated or activated by aggregation of FcεRIα. These findings indicate that initial incubation of human bone marrow CD34+ progenitors with IL-3 does not affect the differentiation of mast cells. PMID:18214796

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

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.

Factors affecting the activity of guanylate cyclase in lysates of human blood platelets.

PubMed Central

Adams, A F; Haslam, R J

1978-01-01

1. Under optimal ionic conditions (4 mM-MnCl2) the specific activity of guanylate cyclase in fresh platelet lysates was about 10nmol of cyclic GMP formed/20 min per mg of protein at 30 degrees C. Activity was 15% of optimum with 10mM-MgCl2 and negligible with 4mM-CaCl2. Synergism between MnCl2 and MgCl2 or CaCl2 was observed when [MnCl2] less than or equal to [GPT]. 2. Lower than optimal specific activities were obtained in assays containing large volumes of platelet lysate, owing to the presence of inhibitory factors that could be removed by ultrafiltration. Adenine nucleotides accounted for less than 50% of the inhibitory activity. 3. Preincubation of lysate for 1 h at 30 degrees C increased the specific activity of platelet guanylate cyclase by about 2-fold. 4. Lubrol PX (1%, w/v) stimulated guanylate cyclase activity by 3--5-fold before preincubation and by about 2-fold after preincubation. Triton X-100 was much less effective. 5. Dithiothreitol inhibited the guanylate cyclase activity of untreated, preincubated and Lubrol PX-treated lysates and prevented activation by preincubation provided that it was added beforehand. 6. Oleate stimulated guanylate cyclase activity 3--4-fold and arachidonate 2--3-fold, whereas palmitate was almost inactive. Pretreatment of lysate with indomethacin did not inhibit this effect of arachidonate. Oleate and arachidonate caused marked stimulation of guanylate cyclase in preincubated lysate, but inhibited the enzyme in Lubrol PX-treated lysate. 7. NaN3 (10mM) increased guanylate cyclase activity by up to 7-fold; this effect was both time- and temperature-dependent. NaN3 did not further activate the enzyme in Lubrol PX-treated lysate. 8. The results indicated that preincubation, Lubrol PX, fatty acids and NaN3 activated platelet guanylate cyclase by different mechanisms. 9. Platelet particulate fractions contained no guanylate cyclase activity detectable in the presence or absence of Lubrol PX that could not be accounted for by

Factors affecting the activity of guanylate cyclase in lysates of human blood platelets.

PubMed

Adams, A F; Haslam, R J

1978-07-15

1. Under optimal ionic conditions (4 mM-MnCl2) the specific activity of guanylate cyclase in fresh platelet lysates was about 10nmol of cyclic GMP formed/20 min per mg of protein at 30 degrees C. Activity was 15% of optimum with 10mM-MgCl2 and negligible with 4mM-CaCl2. Synergism between MnCl2 and MgCl2 or CaCl2 was observed when [MnCl2] less than or equal to [GPT]. 2. Lower than optimal specific activities were obtained in assays containing large volumes of platelet lysate, owing to the presence of inhibitory factors that could be removed by ultrafiltration. Adenine nucleotides accounted for less than 50% of the inhibitory activity. 3. Preincubation of lysate for 1 h at 30 degrees C increased the specific activity of platelet guanylate cyclase by about 2-fold. 4. Lubrol PX (1%, w/v) stimulated guanylate cyclase activity by 3--5-fold before preincubation and by about 2-fold after preincubation. Triton X-100 was much less effective. 5. Dithiothreitol inhibited the guanylate cyclase activity of untreated, preincubated and Lubrol PX-treated lysates and prevented activation by preincubation provided that it was added beforehand. 6. Oleate stimulated guanylate cyclase activity 3--4-fold and arachidonate 2--3-fold, whereas palmitate was almost inactive. Pretreatment of lysate with indomethacin did not inhibit this effect of arachidonate. Oleate and arachidonate caused marked stimulation of guanylate cyclase in preincubated lysate, but inhibited the enzyme in Lubrol PX-treated lysate. 7. NaN3 (10mM) increased guanylate cyclase activity by up to 7-fold; this effect was both time- and temperature-dependent. NaN3 did not further activate the enzyme in Lubrol PX-treated lysate. 8. The results indicated that preincubation, Lubrol PX, fatty acids and NaN3 activated platelet guanylate cyclase by different mechanisms. 9. Platelet particulate fractions contained no guanylate cyclase activity detectable in the presence or absence of Lubrol PX that could not be accounted for by

Human Factors Affecting the Patient's Acceptance of Wireless Biomedical Sensors

NASA Astrophysics Data System (ADS)

Fensli, Rune; Boisen, Egil

In monitoring arrhythmia, the quality of medical data from the ECG sensors may be enhanced by being based on everyday life situations. Hence, the development of wireless biomedical sensors is of growing interest, both to diagnose the heart patient, as well as to adjust the regimen. However, human factors such as emotional barriers and stigmatization, may affect the patient's behavior while wearing the equipment, which in turn may influence quality of data. The study of human factors and patient acceptance is important both in relation to the development of such equipment, as well as in evaluating the quality of data gathered from the individual patient. In this paper, we highlight some important aspects in patient acceptance by comparing results from a preliminary clinical trial with patients using a wireless ECG sensor for three days out-of-hospital service, to available published results from telehomecare projects, and discuss important aspects to be taken into account in future investigations.

Turning lemonade into lemons: Dampening appraisals reduce positive affect and increase negative affect during positive activity scheduling.

PubMed

Burr, Leigh-Anne; Javiad, Mahmood; Jell, Grace; Werner-Seidler, Aliza; Dunn, Barnaby D

2017-04-01

The way individuals appraise positive emotions may modulate affective experience during positive activity scheduling. Individuals may either engage in dampening appraisals (e.g., think "this is too good to last") or amplifying appraisals (e.g., think "I deserve this"). A cross-over randomized design was used to examine the consequences of these appraisal styles. Participants (N = 43) rated positive affect (PA) and negative affect (NA) during four daily walks in pleasant locations, whilst following dampening, emotion-focus amplifying (focusing on how good one feels), self-focus amplifying (focusing on positive self qualities), or control instructions. There was no difference between the two amplifying and control conditions, which all increased PA and reduced NA during the walks. However, the dampening condition significantly differed from all other conditions, reducing PA and increasing NA during the walk. Individual differences in anhedonia symptoms did not significantly moderate the pattern of findings. This evidence supports the view that dampening appraisals may be one mechanism driving anhedonia and may account for why positive activity scheduling can sometimes backfire when utilized in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psychophysiological correlates of affects in human olfaction.

PubMed

Bensafi, M; Rouby, C; Farget, V; Bertrand, B; Vigouroux, M; Holley, A

2002-11-01

Pleasantness and arousal have been identified as the main dimensions of affective responses to environment. Pleasantness is defined as the degree of favorable feelings a subject can experience under given circumstances. Arousal is defined as the degree of excitement (general activation) the subject feels under these circumstances. In visual and auditory modalities, many studies using measures such as facial electromyographic (EMG) activity and skin conductance (SC) have found those parameters to vary as a function of either pleasantness or arousal: for example, facial corrugator EMG activity covaries with the pleasantness dimension, while SC increases together with arousal. The first objective of this research is to study the possible covariation between peripheral measures and pleasantness/arousal in olfaction. We also examined the effect of odor intensity on facial and autonomic variations. The second objective was to investigate whether odors could evoke verbally specific emotions (e.g. joy, anger, fear, surprise, disgust or sadness) and also induce specific patterns of peripheral responses. Participants were exposed to 12 different odors while their facial and autonomic parameters were recorded, and estimated their intensity, pleasantness, and arousal capacity. Then, they chose between seven words for emotions (fear, anger, sadness, surprise, neutral, joy or disgust) to describe their reaction to the odor. As in vision, olfactory pleasantness covaries (negatively) with facial activity of the corrugator muscle, and arousal (positively) with skin conductance. No relationships were observed between physiological changes and variations in perceived intensity. Results also showed that emotions of "disgust" and "joy" were more frequently evoked verbally than any other emotions, and that only facial EMG activity distinguishes them (e.g. "disgust" vs. "joy" and "neutral state"). The results are discussed in terms of possible existence of two brain systems (defensive

ANALYSIS OF HUMAN ACTIVITY DATA FOR USE IN MODELING ENVIRONMENTAL EXPOSURES

EPA Science Inventory

Human activity data are a critical part of exposure models being developed by the US EPA's National Exposure Research Laboratory (NERL). An analysis of human activity data within NERL's Consolidated Human Activity Database (CHAD) was performed in two areas relevant to exposure ...

Salt Reduction in a Model High-Salt Akawi Cheese: Effects on Bacterial Activity, pH, Moisture, Potential Bioactive Peptides, Amino Acids, and Growth of Human Colon Cells.

PubMed

Gandhi, Akanksha; Shah, Nagendra P

2016-04-01

This study evaluated the effects of sodium chloride reduction and its substitution with potassium chloride on Akawi cheese during storage for 30 d at 4 °C. Survival of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium longum) and starter bacteria (Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus), angiotensin-converting enzyme-inhibitory and antioxidant activities, and concentrations of standard amino acids as affected by storage in different brine solutions (10% NaCl, 7.5% NaCl, 7.5% NaCl+KCl [1:1], 5% NaCl, and 5% NaCl+KCl [1:1]) were investigated. Furthermore, viability of human colon cells and human colon cancer cells as affected by the extract showing improved peptide profiles, highest release of amino acids and antioxidant activity (that is, from cheese brined in 7.5% NaCl+KCl) was evaluated. Significant increase was observed in survival of probiotic bacteria in cheeses with low salt after 30 d. Calcium content decreased slightly during storage in all cheeses brined in various solutions. Further, no significant changes were observed in ACE-inhibitory activity and antioxidant activity of cheeses during storage. Interestingly, concentrations of 4 essential amino acids (phenylalanine, tryptophan, valine, and leucine) increased significantly during storage in brine solutions containing 7.5% total salt. Low concentration of cheese extract (100 μg/mL) significantly improved the growth of normal human colon cells, and reduced the growth of human colon cancer cells. Overall, the study revealed that cheese extracts from reduced-NaCl brine improved the growth of human colon cells, and the release of essential amino acids, but did not affect the activities of potential bioactive peptides. © 2016 Institute of Food Technologists®

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Affective Evaluations of and Reactions to Exterior and Interior Vehicle Auditory Quality

NASA Astrophysics Data System (ADS)

Västfjäll, D.; Gulbol, M.-A.; Kleiner, M.; Gärling, T.

2002-08-01

Affective reactions to and evaluations of auditory stimuli are fundamental components of human perception. In three experiments, participants rated their affective reactions (how pleasant I feel) and preferences for these affective reactions (how much I like the way I feel) as well as affective evaluations (how pleasant the sound is) to interior and exterior binaurally recorded vehicle sounds varying in physical properties. Consistent with previous research, it was found that the orthogonal affect dimensions of valence (unpleasant-pleasant) and arousal or activation (deactivation-activation) discriminated between affective reactions induced by the different qualities of the sounds. Moreover, preference for affective reactions was related to both valence and activation. Affective evaluations (powerful-powerless/passive-active and unpleasant-pleasant) correlated significantly with affective reactions to the same sounds in both within-subjects and between-subjects designs. Standard sound quality metrics derived from the sounds correlated, however, poorly with the affective ratings of interior sounds and only moderately with affective ratings of exterior sounds. Taken together, the results suggest that affect is an important component in product auditory quality optimization.

Granule Exocytosis Contributes to Priming and Activation of the Human Neutrophil Respiratory Burst

PubMed Central

Uriarte, Silvia M.; Rane, Madhavi J.; Luerman, Gregory C.; Barati, Michelle T.; Ward, Richard A.; Nauseef, William M.; McLeish, Kenneth R.

2013-01-01

The role of exocytosis in the human neutrophil respiratory burst was determined using a fusion protein (TAT–SNAP-23) containing the HIV transactivator of transcription (TAT) cell-penetrating sequence and the N-terminal SNARE domain of synaptosome-associated protein-23 (SNAP-23). This agent inhibited stimulated exocytosis of secretory vesicles and gelatinase and specific granules but not azurophil granules. GST pulldown showed that TAT–SNAP-23 bound to the combination of vesicle-associated membrane protein-2 and syntaxin-4 but not to either individually. TAT–SNAP-23 reduced phagocytosis-stimulated hydrogen peroxide production by 60% without affecting phagocytosis or generation of HOCl within phagosomes. TAT–SNAP-23 had no effect on fMLF-stimulated superoxide release but significantly inhibited priming of this response by TNF-α and platelet-activating factor. Pretreatment with TAT–SNAP-23 inhibited the increase in plasma membrane expression of gp91phox in TNF-α–primed neutrophils, whereas TNF-α activation of ERK1/2 and p38 MAPK was not affected. The data demonstrate that neutrophil granule exocytosis contributes to phagocytosis-induced respiratory burst activity and plays a critical role in priming of the respiratory burst by increasing expression of membrane components of the NADPH oxidase. PMID:21642540

Influence of Human Sera on the In Vitro Activity of the Echinocandin Caspofungin (MK-0991) against Aspergillus fumigatus

PubMed Central

Chiller, Tom; Farrokhshad, Kouros; Brummer, Elmer; Stevens, David A.

2000-01-01

There have been several reports that the activity of echinocandin antifungal agents is not affected or decreased in the presence of human sera. It is known that these drugs are bound >80% in animal and human sera. The activity of the echinocandin caspofungin (MK-0991), a 1,3-β-d-glucan synthase inhibitor, against Aspergillus fumigatus with and without human sera was studied. Conidia of A. fumigatus in microtest plate wells formed germlings after overnight culture in RPMI 1640. Caspofungin was then added with or without serum, and the germlings were incubated at 37°C for 24 h. Human serum (5%) in RPMI 1640 alone did not significantly inhibit the growth of A. fumigatus in vitro. Caspofungin in RPMI 1640 exhibited dose-dependent inhibition, with concentrations of 0.1 and 0.05 μg/ml inhibiting 24.9% +/− 10.4% and 11.7% +/− 3.6%, respectively (n = 10; P < 0.01). The addition of 5% human serum to caspofungin at 0.1 or 0.05 μg/ml increased the inhibition to 78.6% +/− 5.8% or 58.3% +/− 19.2%, respectively (n = 10; P < 0.01 versus controls and versus the drug without serum). Lower concentrations of serum also potentiated drug activity. The effect of human sera was further seen when using caspofungin that had lost activity (e.g., by storage) against A. fumigatus at 0.1 μg/ml. Inactive caspofungin alone demonstrated no significant inhibition of hyphal growth, whereas the addition of 5% human serum to the inactive drug showed 83% +/− 16.5% inhibition (n = 5; P < 0.01). The restoration of activity of caspofungin was seen at concentrations as low as 0.05% human serum. In contrast to prior reports, this study suggests that human serum acts synergistically with caspofungin to enhance its inhibitory activity in vitro against A. fumigatus. PMID:11083631

Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation

PubMed Central

Shi, Jian; Wang, Xinwen; Nguyen, Jenny; Wu, Audrey H.; Bleske, Barry E.

2016-01-01

Sacubitril was recently approved by the Food and Drug Administration for use in combination with valsartan for the treatment of patients with heart failure with reduced ejection fraction. As a prodrug, sacubitril must be metabolized (hydrolyzed) to its active metabolite sacubitrilat (LBQ657) to exert its intended therapeutic effects. Thus, understanding the determinants of sacubitril activation will lead to the improvement of sacubitril pharmacotherapy. The objective of this study was to identify the enzyme(s) responsible for the activation of sacubitril, and determine the impact of genetic variation on sacubitril activation. First, an incubation study of sacubitril with human plasma and the S9 fractions of human liver, intestine, and kidney was conducted. Sacubitril was found to be activated by human liver S9 fractions only. Moreover, sacubitril activation was significantly inhibited by the carboxylesterase 1 (CES1) inhibitor bis-(p-nitrophenyl) phosphate in human liver S9. Further incubation studies with recombinant human CES1 and carboxylesterase 2 confirmed that sacubitril is a selective CES1 substrate. The in vitro study of cell lines transfected with wild-type CES1 and the CES1 variant G143E (rs71647871) demonstrated that G143E is a loss-of-function variant for sacubitril activation. Importantly, sacubitril activation was significantly impaired in human livers carrying the G143E variant. In conclusion, sacubitril is selectively activated by CES1 in human liver. The CES1 genetic variant G143E can significantly impair sacubitril activation. Therefore, CES1 genetic variants appear to be an important contributing factor to interindividual variability in sacubitril activation, and have the potential to serve as biomarkers to optimize sacubitril pharmacotherapy. PMID:26817948

Distributed affective space represents multiple emotion categories across the human brain

PubMed Central

Saarimäki, Heini; Ejtehadian, Lara Farzaneh; Jääskeläinen, Iiro P; Vuilleumier, Patrik; Sams, Mikko; Nummenmaa, Lauri

2018-01-01

Abstract The functional organization of human emotion systems as well as their neuroanatomical basis and segregation in the brain remains unresolved. Here, we used pattern classification and hierarchical clustering to characterize the organization of a wide array of emotion categories in the human brain. We induced 14 emotions (6 ‘basic’, e.g. fear and anger; and 8 ‘non-basic’, e.g. shame and gratitude) and a neutral state using guided mental imagery while participants' brain activity was measured with functional magnetic resonance imaging (fMRI). Twelve out of 14 emotions could be reliably classified from the haemodynamic signals. All emotions engaged a multitude of brain areas, primarily in midline cortices including anterior and posterior cingulate gyri and precuneus, in subcortical regions, and in motor regions including cerebellum and premotor cortex. Similarity of subjective emotional experiences was associated with similarity of the corresponding neural activation patterns. We conclude that different basic and non-basic emotions have distinguishable neural bases characterized by specific, distributed activation patterns in widespread cortical and subcortical circuits. Regionally differentiated engagement of these circuits defines the unique neural activity pattern and the corresponding subjective feeling associated with each emotion. PMID:29618125

Human β-defensin 4 with non-native disulfide bridges exhibit antimicrobial activity.

PubMed

Sharma, Himanshu; Nagaraj, Ramakrishnan

2015-01-01

Human defensins play multiple roles in innate immunity including direct antimicrobial killing and immunomodulatory activity. They have three disulfide bridges which contribute to the stability of three anti-parallel β-strands. The exact role of disulfide bridges and canonical β-structure in the antimicrobial action is not yet fully understood. In this study, we have explored the antimicrobial activity of human β-defensin 4 (HBD4) analogs that differ in the number and connectivity of disulfide bridges. The cysteine framework was similar to the disulfide bridges present in μ-conotoxins, an unrelated class of peptide toxins. All the analogs possessed enhanced antimicrobial potency as compared to native HBD4. Among the analogs, the single disulfide bridged peptide showed maximum potency. However, there were no marked differences in the secondary structure of the analogs. Subtle variations were observed in the localization and membrane interaction of the analogs with bacteria and Candida albicans, suggesting a role for disulfide bridges in modulating their antimicrobial action. All analogs accumulated in the cytosol where they can bind to anionic molecules such as nucleic acids which would affect several cellular processes leading to cell death. Our study strongly suggests that native disulfide bridges or the canonical β-strands in defensins have not evolved for maximal activity but they play important roles in determining their antimicrobial potency.

Human β-Defensin 4 with Non-Native Disulfide Bridges Exhibit Antimicrobial Activity

PubMed Central

Sharma, Himanshu; Nagaraj, Ramakrishnan

2015-01-01

Human defensins play multiple roles in innate immunity including direct antimicrobial killing and immunomodulatory activity. They have three disulfide bridges which contribute to the stability of three anti-parallel β-strands. The exact role of disulfide bridges and canonical β-structure in the antimicrobial action is not yet fully understood. In this study, we have explored the antimicrobial activity of human β-defensin 4 (HBD4) analogs that differ in the number and connectivity of disulfide bridges. The cysteine framework was similar to the disulfide bridges present in μ-conotoxins, an unrelated class of peptide toxins. All the analogs possessed enhanced antimicrobial potency as compared to native HBD4. Among the analogs, the single disulfide bridged peptide showed maximum potency. However, there were no marked differences in the secondary structure of the analogs. Subtle variations were observed in the localization and membrane interaction of the analogs with bacteria and Candida albicans, suggesting a role for disulfide bridges in modulating their antimicrobial action. All analogs accumulated in the cytosol where they can bind to anionic molecules such as nucleic acids which would affect several cellular processes leading to cell death. Our study strongly suggests that native disulfide bridges or the canonical β-strands in defensins have not evolved for maximal activity but they play important roles in determining their antimicrobial potency. PMID:25785690

Physical Activity, Mind Wandering, Affect, and Sleep: An Ecological Momentary Assessment.

PubMed

Fanning, Jason; Mackenzie, Michael; Roberts, Sarah; Crato, Ines; Ehlers, Diane; McAuley, Edward

2016-08-31

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. 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. 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. 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). 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).

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

Simulation-Based Mission Rehearsal as a Human Activity System.

DTIC Science & Technology

1996-09-01

explain this demonstrated importance of the people involved in MR, a human activity system model of simulation-based rehearsal was developed. It provides...Implications of this human activity system view are discussed, including: places in the mission preparation process where simulation can benefit operations

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 ...

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 ...

Potential Electrostatic Interactions in Multiple Regions Affect Human Metapneumovirus F-Mediated Membrane Fusion

PubMed Central

Chang, Andres; Hackett, Brent A.; Winter, Christine C.; Buchholz, Ursula J.

2012-01-01

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 F2 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. PMID:22761366

Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

PubMed

Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

2017-09-01

The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

Two quantitative trait loci affect ACE activities in Mexican-Americans.

PubMed

Kammerer, Candace M; Gouin, Nicolas; Samollow, Paul B; VandeBerg, Jane F; Hixson, James E; Cole, Shelley A; MacCluer, Jean W; Atwood, Larry D

2004-02-01

Angiotensin-converting enzyme (ACE) activity is highly heritable and has been associated with cardiovascular disease. We are studying the effects of genes and environmental factors on hypertension and related phenotypes, such as ACE activity, in Mexican-American families. In the current study, we performed multipoint linkage analysis to search for quantitative trait loci (QTLs) that affect ACE activities on data from 793 individuals from 29 pedigrees from the San Antonio Family Heart Study. As expected, we obtained strong evidence (maximum log of the odds [LOD]=4.57, genomic P=0.003) that a QTL for ACE activity is located on chromosome 17 near the ACE structural locus. We subsequently performed linkage analyses conditional on the effect of this QTL and obtained strong evidence (LOD=3.34) for a second QTL on chromosome 4 near D4S1548. We next incorporated the ACEIns/Del genotypes in our analyses and removed the evidence for the chromosome 17 QTL (maximum LOD=0.60); however, we retained our evidence for the QTL on chromosome 4q. We conclude that the QTL on chromosome 17 is tightly linked to ACE and is in strong disequilibrium with the insertion/deletion polymorphism, which is consistent with other reports. We also have evidence that an additional QTL affects ACE activity. Identification of this additional QTL might lead to alternate means of prophylaxis.

Human Activity Helps Prey Win the Predator-Prey Space Race

PubMed Central

Muhly, Tyler B.; Semeniuk, Christina; Massolo, Alessandro; Hickman, Laura; Musiani, Marco

2011-01-01

Predator-prey interactions, including between large mammalian wildlife species, can be represented as a “space race”, where prey try to minimize and predators maximize spatial overlap. Human activity can also influence the distribution of wildlife species. In particular, high-human disturbance can displace large carnivore predators, a trait-mediated direct effect. Predator displacement by humans could then indirectly benefit prey species by reducing predation risk, a trait-mediated indirect effect of humans that spatially decouples predators from prey. The purpose of this research was to test the hypothesis that high-human activity was displacing predators and thus indirectly creating spatial refuge for prey species, helping prey win the “space race”. We measured the occurrence of eleven large mammal species (including humans and cattle) at 43 camera traps deployed on roads and trails in southwest Alberta, Canada. We tested species co-occurrence at camera sites using hierarchical cluster and nonmetric multidimensional scaling (NMS) analyses; and tested whether human activity, food and/or habitat influenced predator and prey species counts at camera sites using regression tree analysis. Cluster and NMS analysis indicated that at camera sites humans co-occurred with prey species more than predator species and predator species had relatively low co-occurrence with prey species. Regression tree analysis indicated that prey species were three times more abundant on roads and trails with >32 humans/day. However, predators were less abundant on roads and trails that exceeded 18 humans/day. Our results support the hypothesis that high-human activity displaced predators but not prey species, creating spatial refuge from predation. High-human activity on roads and trails (i.e., >18 humans/day) has the potential to interfere with predator-prey interactions via trait-mediated direct and indirect effects. We urge scientist and managers to carefully consider and quantify

Protective features of resveratrol on human spermatozoa cryopreservation may be mediated through 5' AMP-activated protein kinase activation.

PubMed

Shabani Nashtaei, M; Amidi, F; Sedighi Gilani, M A; Aleyasin, A; Bakhshalizadeh, Sh; Naji, M; Nekoonam, S

2017-03-01

Biochemical and physical modifications during the freeze-thaw process adversely influence the restoration of energy-dependent sperm functions required for fertilization. Resveratrol, a phytoalexin, has been introduced to activate 5' AMP-activated protein kinase which is a cell energy sensor and a cell metabolism regulator. The cryoprotection of resveratrol on sperm cryoinjury via activation of AMP-activated protein kinase also remains to be elucidated. Our aim, thus, was to investigate: (i) the presence and intracellular localization of AMP-activated protein kinase protein; (ii) whether resveratrol may exert a protective effect on certain functional properties of fresh and post-thaw human spermatozoa through modulation of AMP-activated protein kinase. Spermatozoa from normozoospermic men were incubated with or without different concentrations of Compound C as an AMP-activated protein kinase inhibitor or resveratrol as an AMP-activated protein kinase activator for different lengths of time and were then cryopreserved. AMP-activated protein kinase is expressed essentially in the entire flagellum and the post-equatorial region. Viability of fresh spermatozoa was not significantly affected by the presence of Compound C or resveratrol. However, although Compound C caused a potent inhibition of spermatozoa motility parameters, resveratrol did not induce negative effect, except a significant reduction in motility at 25 μm for 1 h. Furthermore, resveratrol significantly increased AMP-activated protein kinase phosphorylation and mitochondrial membrane potential and decreased reactive oxygen species and apoptosis-like changes in frozen-thawed spermatozoa. Nevertheless, it was not able to compensate decreased sperm viability and motility parameters following cryopreservation. In contrast, Compound C showed opposite effects to resveratrol on AMP-activated protein kinase phosphorylation, reactive oxygen species, apoptosis-like changes, mitochondrial membrane potential, and

Diisopropylfluorophosphate-sensitive aryl acylamidase activity of fatty acid free human serum albumin.

PubMed

Manoharan, Indumathi; Boopathy, Rathnam

2006-08-15

Butyrylcholinesterase in human plasma and acetylcholinesterase in human red blood cells have aryl acylamidase activity toward o-nitroacetanilide, hydrolyzing the amide bond to produce o-nitroaniline and acetate. People with a genetic variant of butyrylcholinesterase that had no detectable activity with butyrylthiocholine, nevertheless had aryl acylamidase activity in their plasma. To determine the source of this aryl acylamidase activity we tested fatty acid free human albumin for activity. We found that albumin had aryl acylacylamidase activity and that this activity was inhibited by diisopropylfluorophosphate. Since the esterase activity of albumin is also inhibited by diisopropylfluorophosphate, and since it is known that diisopropylfluorophosphate covalently binds to Tyr 411 of human albumin, we conclude that the active site for aryl acylamidase activity of albumin is Tyr 411. Albumin accounts for about 10% of the aryl acylamidase activity in human plasma.

Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation.

PubMed

Shi, Jian; Wang, Xinwen; Nguyen, Jenny; Wu, Audrey H; Bleske, Barry E; Zhu, Hao-Jie

2016-04-01

Sacubitril was recently approved by the Food and Drug Administration for use in combination with valsartan for the treatment of patients with heart failure with reduced ejection fraction. As a prodrug, sacubitril must be metabolized (hydrolyzed) to its active metabolite sacubitrilat (LBQ657) to exert its intended therapeutic effects. Thus, understanding the determinants of sacubitril activation will lead to the improvement of sacubitril pharmacotherapy. The objective of this study was to identify the enzyme(s) responsible for the activation of sacubitril, and determine the impact of genetic variation on sacubitril activation. First, an incubation study of sacubitril with human plasma and the S9 fractions of human liver, intestine, and kidney was conducted. Sacubitril was found to be activated by human liver S9 fractions only. Moreover, sacubitril activation was significantly inhibited by the carboxylesterase 1 (CES1) inhibitor bis-(p-nitrophenyl) phosphate in human liver S9. Further incubation studies with recombinant human CES1 and carboxylesterase 2 confirmed that sacubitril is a selective CES1 substrate. The in vitro study of cell lines transfected with wild-type CES1 and the CES1 variant G143E (rs71647871) demonstrated that G143E is a loss-of-function variant for sacubitril activation. Importantly, sacubitril activation was significantly impaired in human livers carrying the G143E variant. In conclusion, sacubitril is selectively activated by CES1 in human liver. The CES1 genetic variant G143E can significantly impair sacubitril activation. Therefore, CES1 genetic variants appear to be an important contributing factor to interindividual variability in sacubitril activation, and have the potential to serve as biomarkers to optimize sacubitril pharmacotherapy. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Response of ESV to Climate Change and Human Activities in the Yanqi Basin, Xinjiang, China

NASA Astrophysics Data System (ADS)

Rusuli, Yusufujiang; Sidik, Halida; Gupur, Adila; Hong, Jiang; Kadir, Rayila

2016-04-01

Ecosystem goods and services refer to the dependence of economic wealth and human well-being on natural systems. It is a common knowledge that the changing of structure and function of the ecosystem due to climate change and human activities. It is a priority issue to study on various spatiotemporal scales, the sensitivity of ecosystems to climate change and anthropogenic pressure in inland areas. In an effort to better understand the influence of climate change and human activities on ecosystem services, we evaluated the change in ESV of the Yanqi Basin in Xinjiang, China from 1973 to 2014 employing methods of MK, MK Sneyers, ESV and dynamic degree of LUCC. The Landsat images, digital elevation model (DEM) and metrological data were applied to assessing the ESV and its change. According to the degree of effects of the climate change and human activities, the research area was divided into two parts: the mountain area and the plain oasis area at a contour of 1400 m above sea level. According to type and affect, the land cover was classified as water, wetland, desert, fields, glacier, warm shrub grassland, cold meadow steppe and highland vegetation. We analyzed the relationship between the variation of ESV and precipitation, and evaporation and then quantitatively differentiated the influence of climate change and human activities on ESV. Results show that: (1) distinct change points of precipitation and evaporation in mountain and plain oasis of the Yanqi basin were detected by the MK-Sneyers test. The precipitation increased and the evaporation declined in mountain and plain oasis in the same way. Enlargement of agricultural areas to accommodate an increased population and socio-economic development was detected by conversion matrix of LUCC in oasis area. As a result, the variation of ESV was caused by climate change and human activities jointly; (2) the declining trend of ESV in the mountain area was mainly caused by shrinking of the glacier area; (3) ESV was

The role of sense of coherence and physical activity in positive and negative affect of Turkish adolescents.

PubMed

Oztekin, Ceyda; Tezer, Esin

2009-01-01

This study investigated the role of sense of coherence and total physical activity in positive and negative affect. Participants were 376 (169 female, 206 male, and 1 missing value) student volunteers from different faculties of Middle East Technical University. Three questionnaires: Sense of Coherence Scale (SOC), Physical Activity Assessment Questionnaire (PAAQ), and Positive and Negative Affect Schedule (PANAS) were administered to the students together with the demographic information sheet. Two separate stepwise multiple linear regression analyses were conducted to examine the predictive power of sense of coherence and total physical activity on positive and negative affect scores. Results revealed that both sense of coherence and total physical activity predicted the positive affect whereas only the sense of coherence predicted the negative affect on university students. Findings are discussed in light of sense of coherence, physical activity, and positive and negative affect literature.

The spatial relationship between human activities and C, N, P, S in soil based on landscape geochemical interpretation.

PubMed

Yu, Huan; He, Zheng-Wei; Kong, Bo; Weng, Zhong-Yin; Shi, Ze-Ming

2016-04-01

The development and formation of chemical elements in soil are affected not only by parent material, climate, biology, and topology factors, but also by human activities. As the main elements supporting life on earth system, the C, N, P, S cycles in soil have been altered by human activity through land-use change, agricultural intensification, and use of fossil fuels. The present study attempts to analyze whether and how a connection can be made between macroscopical control and microcosmic analysis, to estimate the impacts of human activities on C, N, P, S elements in soil, and to determine a way to describe the spatial relationship between C, N, P, S in soil and human activities, by means of landscape geochemical theories and methods. In addition, the disturbances of human activities on C, N, P, S are explored through the analysis of the spatial relationship between human disturbed landscapes and element anomalies, thereby determining the diversified rules of the effects. The study results show that the rules of different landscapes influencing C, N, P, S elements are diversified, and that the C element is closely related to city landscapes; furthermore, the elements N, P, and S are shown to be closely related to river landscapes; the relationships between mine landscapes and the elements C, N, P, S are apparent; the relationships between the elements C, N, P, S and road landscapes are quite close, which shows that road landscapes have significant effects on these elements. Therefore, the conclusion is drawn that the response mechanism analysis of human disturbance and soil chemical element aggregation is feasible, based on the landscape geochemical theories and methods. The spatial information techniques, such as remote sensing and geographic information systems, are effective for research on soil element migration.

Changes in behaviour and faecal glucocorticoid levels in response to increased human activities during weekends in the pin-tailed sandgrouse.

PubMed

Casas, Fabián; Benítez-López, Ana; Tarjuelo, Rocío; Barja, Isabel; Viñuela, Javier; García, Jesús T; Morales, Manuel B; Mougeot, Francois

2016-12-01

Human recreational activities are becoming increasingly widespread and frequent, a fact that may potentially exacerbate their effects on wildlife. These human-related disturbances on animals may induce behavioural and physiological changes that can ultimately affect their fitness, showing a similar anti-predator response that against natural predator or other threats. Here, we combine the use of behavioural and physiological approaches to assess the potential effect of winter human activities on a threatened farmland bird in Europe, the pin-tailed sandgrouse (Pterocles alchata). We compared before, during and after weekend variations in human activity rates, pin-tailed sandgrouse behaviour (flocking and flying behaviour, interspecific association in mixed flocks and habitat use) and faecal glucocorticoid metabolite concentrations. Human disturbances, in particular those associated with hunting activities, peaked during weekends. Sandgrouse showed significant behavioural changes (increased sandgrouse-only flock sizes, increased proportion of birds flying and changes in habitat use) during weekends and higher faecal glucocorticoid metabolite concentrations after the weekends compared with during or before weekends. Therefore, physiological stress levels could be modulated by behavioural adjustments such as increased flock sizes and changes in habitat use that may allow sandgrouse to cope with increased human disturbance rates during weekends. Nevertheless, temporal and spatial organization of hunting days among groups of estates might be good strategies to buffer these potential adverse effects on wintering pin-tailed sandgrouse and other steppe species of conservation concern, while preserving a socio-economically important activity such as hunting.

Changes in behaviour and faecal glucocorticoid levels in response to increased human activities during weekends in the pin-tailed sandgrouse

NASA Astrophysics Data System (ADS)

Casas, Fabián; Benítez-López, Ana; Tarjuelo, Rocío; Barja, Isabel; Viñuela, Javier; García, Jesús T.; Morales, Manuel B.; Mougeot, Francois

2016-12-01

Human recreational activities are becoming increasingly widespread and frequent, a fact that may potentially exacerbate their effects on wildlife. These human-related disturbances on animals may induce behavioural and physiological changes that can ultimately affect their fitness, showing a similar anti-predator response that against natural predator or other threats. Here, we combine the use of behavioural and physiological approaches to assess the potential effect of winter human activities on a threatened farmland bird in Europe, the pin-tailed sandgrouse ( Pterocles alchata). We compared before, during and after weekend variations in human activity rates, pin-tailed sandgrouse behaviour (flocking and flying behaviour, interspecific association in mixed flocks and habitat use) and faecal glucocorticoid metabolite concentrations. Human disturbances, in particular those associated with hunting activities, peaked during weekends. Sandgrouse showed significant behavioural changes (increased sandgrouse-only flock sizes, increased proportion of birds flying and changes in habitat use) during weekends and higher faecal glucocorticoid metabolite concentrations after the weekends compared with during or before weekends. Therefore, physiological stress levels could be modulated by behavioural adjustments such as increased flock sizes and changes in habitat use that may allow sandgrouse to cope with increased human disturbance rates during weekends. Nevertheless, temporal and spatial organization of hunting days among groups of estates might be good strategies to buffer these potential adverse effects on wintering pin-tailed sandgrouse and other steppe species of conservation concern, while preserving a socio-economically important activity such as hunting.

Human activities cause distinct dissolved organic matter composition across freshwater ecosystems.

PubMed

Williams, Clayton J; Frost, Paul C; Morales-Williams, Ana M; Larson, James H; Richardson, William B; Chiandet, Aisha S; Xenopoulos, Marguerite A

2016-02-01

Dissolved organic matter (DOM) composition in freshwater ecosystems is influenced by the interactions among physical, chemical, and biological processes that are controlled, at one level, by watershed landscape, hydrology, and their connections. Against this environmental template, humans may strongly influence DOM composition. Yet, we lack a comprehensive understanding of DOM composition variation across freshwater ecosystems differentially affected by human activity. Using optical properties, we described DOM variation across five ecosystem groups of the Laurentian Great Lakes region: large lakes, Kawartha Lakes, Experimental Lakes Area, urban stormwater ponds, and rivers (n = 184 sites). We determined how between ecosystem variation in DOM composition related to watershed size, land use and cover, water quality measures (conductivity, dissolved organic carbon (DOC), nutrient concentration, chlorophyll a), and human population density. The five freshwater ecosystem groups had distinctive DOM composition from each other. These significant differences were not explained completely through differences in watershed size nor spatial autocorrelation. Instead, multivariate partial least squares regression showed that DOM composition was related to differences in human impact across freshwater ecosystems. In particular, urban/developed watersheds with higher human population densities had a unique DOM composition with a clear anthropogenic influence that was distinct from DOM composition in natural land cover and/or agricultural watersheds. This nonagricultural, human developed impact on aquatic DOM was most evident through increased levels of a microbial, humic-like parallel factor analysis component (C6). Lotic and lentic ecosystems with low human population densities had DOM compositions more typical of clear water to humic-rich freshwater ecosystems but C6 was only present at trace to background levels. Consequently, humans are strongly altering the quality of DOM in

Human activities cause distinct dissolved organic matter composition across freshwater ecosystems

USGS Publications Warehouse

Williams, Clayton J.; Frost, Paul C.; Morales-Williams, Ana M.; Larson, James H.; Richardson, William B.; Chiandet, Aisha S.; Xenopoulos, Marguerite A.

2016-01-01

Dissolved organic matter (DOM) composition in freshwater ecosystems is influenced by interactions between physical, chemical, and biological processes that are controlled, at one level, by watershed landscape, hydrology, and their connections. Against this environmental template, humans may strongly influence DOM composition. Yet, we lack a comprehensive understanding of DOM composition variation across freshwater ecosystems differentially affected by human activity. Using optical properties, we described DOM variation across five ecosystem groups of the Laurentian Great Lakes Region: large lakes, Kawartha Lakes, Experimental Lakes Area, urban stormwater ponds, and rivers (n = 184 sites). We determined how between ecosystem variation in DOM composition related to watershed size, land use and cover, water quality measures (conductivity, dissolved organic carbon (DOC), nutrient concentration, chlorophyll a), and human population density. The five freshwater ecosystem groups had distinctive DOM composition from each other. These significant differences were not explained completely through differences in watershed size nor spatial autocorrelation. Instead, multivariate partial least squares regression showed that DOM composition was related to differences in human impact across freshwater ecosystems. In particular, urban/developed watersheds with higher human population densities had a unique DOM composition with a clear anthropogenic influence that was distinct from DOM composition in natural land cover and/or agricultural watersheds. This nonagricultural, human developed impact on aquatic DOM was most evident through increased levels of a microbial, humic-like parallel factor analysis component (C6). Lotic and lentic ecosystems with low human population densities had DOM compositions more typical of clear water to humic-rich freshwater ecosystems but C6 was only present at trace to background levels. Consequently, humans are strongly altering the quality of DOM in

Ecology of conflict: marine food supply affects human-wildlife interactions on land.

PubMed

Artelle, Kyle A; Anderson, Sean C; Reynolds, John D; Cooper, Andrew B; Paquet, Paul C; Darimont, Chris T

2016-05-17

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/km(2) 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 1(st)), 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.

Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks

PubMed Central

Lipovich, Leonard; Dachet, Fabien; Cai, Juan; Bagla, Shruti; Balan, Karina; Jia, Hui; Loeb, Jeffrey A.

2012-01-01

While most gene transcription yields RNA transcripts that code for proteins, a sizable proportion of the genome generates RNA transcripts that do not code for proteins, but may have important regulatory functions. The brain-derived neurotrophic factor (BDNF) gene, a key regulator of neuronal activity, is overlapped by a primate-specific, antisense long noncoding RNA (lncRNA) called BDNFOS. We demonstrate reciprocal patterns of BDNF and BDNFOS transcription in highly active regions of human neocortex removed as a treatment for intractable seizures. A genome-wide analysis of activity-dependent coding and noncoding human transcription using a custom lncRNA microarray identified 1288 differentially expressed lncRNAs, of which 26 had expression profiles that matched activity-dependent coding genes and an additional 8 were adjacent to or overlapping with differentially expressed protein-coding genes. The functions of most of these protein-coding partner genes, such as ARC, include long-term potentiation, synaptic activity, and memory. The nuclear lncRNAs NEAT1, MALAT1, and RPPH1, composing an RNAse P-dependent lncRNA-maturation pathway, were also upregulated. As a means to replicate human neuronal activity, repeated depolarization of SY5Y cells resulted in sustained CREB activation and produced an inverse pattern of BDNF-BDNFOS co-expression that was not achieved with a single depolarization. RNAi-mediated knockdown of BDNFOS in human SY5Y cells increased BDNF expression, suggesting that BDNFOS directly downregulates BDNF. Temporal expression patterns of other lncRNA-messenger RNA pairs validated the effect of chronic neuronal activity on the transcriptome and implied various lncRNA regulatory mechanisms. lncRNAs, some of which are unique to primates, thus appear to have potentially important regulatory roles in activity-dependent human brain plasticity. PMID:22960213

Oxidative stress negatively affects human sperm mitochondrial respiration.

PubMed

Ferramosca, Alessandra; Pinto Provenzano, Sara; Montagna, Daniela Domenica; Coppola, Lamberto; Zara, Vincenzo

2013-07-01

To correlate the level of oxidative stress in serum and seminal fluid and the level of sperm deoxyribonucleic acid (DNA) fragmentation with sperm mitochondrial respiratory efficiency. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption carried out in hypotonically treated sperm cells. A possible relationship between sperm mitochondrial respiratory efficiency, the level of oxidative stress, and the level of sperm DNA fragmentation was investigated. Sperm motility was positively correlated with mitochondrial respiration but negatively correlated with oxidative stress and DNA fragmentation. Interestingly, sperm mitochondrial respiratory activity was negatively affected by oxidative stress and DNA fragmentation. Our data indicate that sperm mitochondrial respiration is decreased in patients with high levels of reactive oxygen species by an uncoupling between electron transport and adenosine triphosphate synthesis. This reduction in mitochondrial functionality might be 1 of the reasons responsible for the decrease in spermatozoa motility. Copyright © 2013 Elsevier Inc. All rights reserved.

Smad4 inhibits cell migration via suppression of JNK activity in human pancreatic carcinoma PANC-1 cells.

PubMed

Zhang, Xueying; Cao, Junxia; Pei, Yujun; Zhang, Jiyan; Wang, Qingyang

2016-05-01

Smad4 is a common Smad and is a key downstream regulator of the transforming growth factor-β signaling pathway, in which Smad4 often acts as a potent tumor suppressor and functions in a highly context-dependent manner, particularly in pancreatic cancer. However, little is known regarding whether Smad4 regulates other signaling pathways involved in pancreatic cancer. The present study demonstrated that Smad4 downregulates c-Jun N-terminal kinase (JNK) activity using a Smad4 loss-of-function or gain-of-function analysis. Additionally, stable overexpression of Smad4 clearly affected the migration of human pancreatic epithelioid carcinoma PANC-1 cells, but did not affect cell growth. In addition, the present study revealed that upregulation of mitogen-activated protein kinase phosphatase-1 is required for the reduction of JNK activity by Smad4, leading to a decrease in vascular endothelial growth factor expression and inhibiting cell migration. Overall, the present findings indicate that Smad4 may suppress JNK activation and inhibit the tumor characteristics of pancreatic cancer cells.

Human Activity Recognition Supported on Indoor Localization: A Systematic Review.

PubMed

Cerón, Jesús; López, Diego M

2018-01-01

The number of older adults is growing worldwide. This has a social and economic impact in all countries because of the increased number of older adults affected by chronic diseases, health emergencies, and disabilities, representing at the end high cost for the health system. To face this problem, the Ambient Assisted Living (AAL) domain has emerged. Its main objective is to extend the time that older adults can live independently in their homes. AAL is supported by different fields and technologies, being Human Activity Recognition (HAR), control of vital signs and location tracking the three of most interest during the last years. To perform a systematic review about Human Activity Recognition (HAR) approaches supported on Indoor Localization (IL) and vice versa, describing the methods they have used, the accuracy they have obtained and whether they have been directed towards the AAL domain or not. A systematic review of six databases was carried out (ACM, IEEE Xplore, PubMed, Science Direct and Springer). 27 papers were found. They were categorised into three groups according their approach: paper focus on 1. HAR, 2. IL, 3. HAR and IL. A detailed analysis of the following factors was performed: type of methods and technologies used for HAR, IL and data fusion, as well as the precision obtained for them. This systematic review shows that the relationship between HAR and IL has been very little studied, therefore providing insights of its potential mutual support to provide AAL solutions.

Fermentation properties of isomaltooligosaccharides are affected by human fecal enterotypes.

PubMed

Wu, Qinqin; Pi, Xiong'e; Liu, Wei; Chen, Huahai; Yin, Yeshi; Yu, Hongwei D; Wang, Xin; Zhu, Liying

2017-12-01

Isomaltooligosaccharides (IMOs) are enzymatically synthesized oligosaccharides that have potential prebiotic effects. Five IMO substrates with 2-16° of polymerization (DP) were studied for their fermentation capacities using human microbiomes in an in vitro batch fermentation model. Eleven fecal slurries belonging to three enterotypes, including the Bacteroides-, Prevotella- and Mixed-type, exhibited different degradation rates for long chain IMOs (DP 7 to 16). In contrast, the degradation rates for short chain IMOs (DP 2 to 6) were not affected by enterotypes. Both 16S rRNA gene sequencing and quantitative PCR demonstrated that, after fermentation, the Bifidobacterium growth with IMOs was primarily detected in the Bacteroides- and Mixed-type (non-Prevotella-type), and to a lesser degree in the Prevotella-type. Interestingly, the Prevotella-type microbiome had higher levels of propionic acid and butyric acid production than non-Prevotella-type microbiome after IMOs fermentation. Moreover, principal coordinate analysis (PCoA) of both denaturing gradient gel electrophoresis (DGGE) profiling and 16S rRNA sequencing data demonstrated that the microbiome community compositions were separately clustered based on IMO chain length, suggesting significant impact of DP on the bacterial community structure. The current results clearly demonstrated that the IMO chain length could modulate the structure and composition of the human colonic microbiome. Different responses to short and long chain IMOs were observed from three human enterotypes, indicating that IMOs may be used as therapeutic substrates for directly altering human colonic bacteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human milk proteins: key components for the biological activity of human milk.

PubMed

Lönnerdal, Bo

2004-01-01

Human milk contains a wide array of proteins that provide biologic activities ranging from antimicrobial effects to immunostimulatory functions. Proteins like lactoferrin, secretory IgA, kappa-casein, lactoperoxidase, haptocorrin, lactadherin and peptides formed from human milk proteins during digestion can inhibit the growth of pathogenic bacteria and viruses and therefore protect against infection. At the same time, proteins like lactoferrin, bile-salt stimulated lipase, haptocorrin, kappa-casein, and folate-binding protein can facilitate the absorption of nutrients in the neonatal gut. However, the proteins in human milk themselves also provide adequate amounts of essential amino acids to the growing infant. This suggests a highly adapted digestive system, which allows the survival of some proteins and peptides in the upper gastrointestinal tract, while still allowing amino acid utilization from these proteins further down in the gut. It is now possible to produce recombinant human milk proteins in transgenic plants and animals, which makes it possible to further study the bioactivity of these proteins. Provided these proteins can be produced in large scale at low cost, that they show biologic activity and pose no safety concerns, it may be possible to add some human milk proteins to infant diets, such as formula and complementary foods. Human milk proteins produced in rice or potatoes, for example, could be added without much purification, because these staples commonly are used in weaning foods. Thus, some qualities provided by human milk may be included into other diets, although it is highly unlikely that all unique components of human milk can be copied this way.

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. © 2015 Schmidt and Cech Published by Cold Spring Harbor Laboratory Press.

Decoding negative affect personality trait from patterns of brain activation to threat stimuli.

PubMed

Fernandes, Orlando; Portugal, Liana C L; Alves, Rita de Cássia S; Arruda-Sanchez, Tiago; Rao, Anil; Volchan, Eliane; Pereira, Mirtes; Oliveira, Letícia; Mourao-Miranda, Janaina

2017-01-15

Pattern recognition analysis (PRA) applied to functional magnetic resonance imaging (fMRI) has been used to decode cognitive processes and identify possible biomarkers for mental illness. In the present study, we investigated whether the positive affect (PA) or negative affect (NA) personality traits could be decoded from patterns of brain activation in response to a human threat using a healthy sample. fMRI data from 34 volunteers (15 women) were acquired during a simple motor task while the volunteers viewed a set of threat stimuli that were directed either toward them or away from them and matched neutral pictures. For each participant, contrast images from a General Linear Model (GLM) between the threat versus neutral stimuli defined the spatial patterns used as input to the regression model. We applied a multiple kernel learning (MKL) regression combining information from different brain regions hierarchically in a whole brain model to decode the NA and PA from patterns of brain activation in response to threat stimuli. The MKL model was able to decode NA but not PA from the contrast images between threat stimuli directed away versus neutral with a significance above chance. The correlation and the mean squared error (MSE) between predicted and actual NA were 0.52 (p-value=0.01) and 24.43 (p-value=0.01), respectively. The MKL pattern regression model identified a network with 37 regions that contributed to the predictions. Some of the regions were related to perception (e.g., occipital and temporal regions) while others were related to emotional evaluation (e.g., caudate and prefrontal regions). These results suggest that there was an interaction between the individuals' NA and the brain response to the threat stimuli directed away, which enabled the MKL model to decode NA from the brain patterns. To our knowledge, this is the first evidence that PRA can be used to decode a personality trait from patterns of brain activation during emotional contexts

Factors That Influence Human Behavior And Negatively Affect Energy Consumption In USMC Ground Units During Operations

DTIC Science & Technology

2016-09-01

vehicle idling, energy strategy, energy behavior, energy reductions, behavior change 15. NUMBER OF PAGES 79 16. PRICE CODE 17. SECURITY...INFLUENCE HUMAN BEHAVIOR AND NEGATIVELY AFFECT ENERGY CONSUMPTION IN USMC GROUND UNITS DURING OPERATIONS by John A. Peters September 2016...NEGATIVELY AFFECT ENERGY CONSUMPTION IN USMC GROUND UNITS DURING OPERATIONS 5. FUNDING NUMBERS 6. AUTHOR(S) John A. Peters 7. PERFORMING

Situational motivation and perceived intensity: their interaction in predicting changes in positive affect from physical activity.

PubMed

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.

Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis.

PubMed

Vaucher, Laurent; Funaro, Michael G; Mehta, Akanksha; Mielnik, Anna; Bolyakov, Alexander; Prossnitz, Eric R; Schlegel, Peter N; Paduch, Darius A

2014-01-01

Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

Can human activities alter the drowning fate of barrier islands?

NASA Astrophysics Data System (ADS)

Lorenzo-Trueba, J.; Ashton, A. D.; Jin, D.; Hoagland, P.; Kite-Powell, H.

2012-12-01

Low-lying coastal barriers face an uncertain future over the coming century and beyond as sea levels rise, with many projections suggesting end-of-century rates of sea-level rise as high or higher than 1 cm/yr. Geologically, such rates of sea-level rise have been experienced several thousand years ago and we can use our understanding of geological processes and sedimentary evidence to help unravel the dynamics of natural barriers experiencing sea-level rise. Along many modern coastal barriers, however, anthropic change, such as beach nourishment, dune construction, and emplacement of hard structures, plays a dominant role in coastline dynamics. A fundamental question to be addressed is whether human activities intended to preserve infrastructure and beach recreation may make wholesale collapse, or 'drowning,' of barrier systems more likely. Here we present a numerical modeling tool that couples natural processes and the human responses to these changes (and the subsequent of human responses on natural processes). Recent theoretical model development suggests that barriers are intrinsically morphodynamic features, responding to sea-level rise in complex ways through the interactions of marine processes and barrier overwash. Undeveloped coastal barriers would therefore respond to an accelerated sea-level rise in complex, less predictable manners than suggested by existing long-term models. We have developed a model that examines non-equilibrium cross-shore evolution of barrier systems at decadal to centennial temporal scales, focusing on the interactions between processes of shoreface evolution and overwash deposition. Model responses demonstrate two means of barrier collapse during sea-level rise: 'height drowning', which occurs when overwash fluxes are insufficient to maintain the landward migration rate required to keep in pace with sea-level rise, and 'width drowning', which occurs when the shoreface response is insufficient to maintain the barrier geometry

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 (c) 2016 APA, all rights reserved).

Stochasticity in Natural Forage Production Affects Use of Urban Areas by Black Bears: Implications to Management of Human-Bear Conflicts

PubMed Central

Baruch-Mordo, Sharon; Wilson, Kenneth R.; Lewis, David L.; Broderick, John; Mao, Julie S.; Breck, Stewart W.

2014-01-01

The rapid expansion of global urban development is increasing opportunities for wildlife to forage and become dependent on anthropogenic resources. Wildlife using urban areas are often perceived dichotomously as urban or not, with some individuals removed in the belief that dependency on anthropogenic resources is irreversible and can lead to increased human-wildlife conflict. For American black bears (Ursus americanus), little is known about the degree of bear urbanization and its ecological mechanisms to guide the management of human-bear conflicts. Using 6 years of GPS location and activity data from bears in Aspen, Colorado, USA, we evaluated the degree of bear urbanization and the factors that best explained its variations. We estimated space use, activity patterns, survival, and reproduction and modeled their relationship with ecological covariates related to bear characteristics and natural food availability. Space use and activity patterns were dependent on natural food availability (good or poor food years), where bears used higher human density areas and became more nocturnal in poor food years. Patterns were reversible, i.e., individuals using urban areas in poor food years used wildland areas in subsequent good food years. While reproductive output was similar across years, survival was lower in poor food years when bears used urban areas to a greater extent. Our findings suggest that bear use of urban areas is reversible and fluctuates with the availability of natural food resources, and that removal of urban individuals in times of food failures has the potential to negatively affect bear populations. Given that under current predictions urbanization is expected to increase by 11% across American black bear range, and that natural food failure years are expected to increase in frequency with global climate change, alternative methods of reducing urban human-bear conflict are required if the goal is to prevent urban areas from becoming population sinks

Stochasticity in natural forage production affects use of urban areas by black bears: implications to management of human-bear conflicts.

PubMed

Baruch-Mordo, Sharon; Wilson, Kenneth R; Lewis, David L; Broderick, John; Mao, Julie S; Breck, Stewart W

2014-01-01

The rapid expansion of global urban development is increasing opportunities for wildlife to forage and become dependent on anthropogenic resources. Wildlife using urban areas are often perceived dichotomously as urban or not, with some individuals removed in the belief that dependency on anthropogenic resources is irreversible and can lead to increased human-wildlife conflict. For American black bears (Ursus americanus), little is known about the degree of bear urbanization and its ecological mechanisms to guide the management of human-bear conflicts. Using 6 years of GPS location and activity data from bears in Aspen, Colorado, USA, we evaluated the degree of bear urbanization and the factors that best explained its variations. We estimated space use, activity patterns, survival, and reproduction and modeled their relationship with ecological covariates related to bear characteristics and natural food availability. Space use and activity patterns were dependent on natural food availability (good or poor food years), where bears used higher human density areas and became more nocturnal in poor food years. Patterns were reversible, i.e., individuals using urban areas in poor food years used wildland areas in subsequent good food years. While reproductive output was similar across years, survival was lower in poor food years when bears used urban areas to a greater extent. Our findings suggest that bear use of urban areas is reversible and fluctuates with the availability of natural food resources, and that removal of urban individuals in times of food failures has the potential to negatively affect bear populations. Given that under current predictions urbanization is expected to increase by 11% across American black bear range, and that natural food failure years are expected to increase in frequency with global climate change, alternative methods of reducing urban human-bear conflict are required if the goal is to prevent urban areas from becoming population sinks.

Identification of amino acid residues involved in the dRP-lyase activity of human Pol ι.

PubMed

Miropolskaya, Nataliya; Petushkov, Ivan; Kulbachinskiy, Andrey; Makarova, Alena V

2017-08-31

Besides X-family DNA polymerases (first of all, Pol β) several other human DNA polymerases from Y- and A- families were shown to possess the dRP-lyase activity and could serve as backup polymerases in base excision repair (Pol ι, Rev1, Pol γ and Pol θ). However the exact position of the active sites and the amino acid residues involved in the dRP-lyase activity in Y- and A- family DNA polymerases are not known. Here we carried out functional analysis of fifteen amino acid residues possibly involved in the dRP-lyase activity of human Pol ι. We show that substitutions of residues Q59, K60 and K207 impair the dRP-lyase activity of Pol ι while residues in the HhH motif of the thumb domain are dispensable for this activity. While both K60G and K207A substitutions decrease Schiff-base intermediate formation during dRP group cleavage, the latter substitution also strongly affects the DNA polymerase activity of Pol ι, suggesting that it may impair DNA binding. These data are consistent with an important role of the N-terminal region in the dRP-lyase activity of Pol ι, with possible involvement of residues from the finger domain in the dRP group cleavage.

Factor Affecting Transplant Outcomes in Diabetic Nude Mice Receiving Human, Porcine, and Non-Human Primate Islets: Analysis of 335 Transplantations

PubMed Central

Loganathan, Gopalakrishnan; Graham, Melanie L.; Radosevich, David M.; Soltani, Sajjad M.; Tiwari, Mukesh; Anazawa, Takayuki; papas, Klearchos K.; Sutherland, David E.R.; Hering, Bernhard J.; Balamurugan, A.N.

2013-01-01

Background In the absence of a reliable islet potency assay, nude mice transplant is the criterion standard to assess islet quality for clinical transplantation. There are factors other than islet quality that affect the transplant outcome. Methods Here, we analyzed the transplant outcomes in 335 nude mice (NM) receiving islets from human (n=103), porcine (n=205), and non-human primate (NHP) donors (n=27). The islets (750, 1000, and 2000 islet equivalents) were transplanted under the kidney capsule of streptozotocin (STZ) induced diabetic NM. Results The proportion of mice that achieved normoglycemia was significantly higher in the group implanted with 2000 IEQ of human, porcine, or NHP islets (75% normoglycemic) versus groups that were implanted with 750 IEQ (7% normoglycemic) and 1000 IEQ (30% normoglycemic). In this study, we observed that the purity of porcine islet preparations (P ≤ .001), islet pellet size in porcine preparations (P ≤ .01) and mice recipient body weight for human islets preparations (P =.013), was independently associated with successful transplant outcome. NHP islets of 1000 IEQ were sufficient to achieve normoglycemic condition (83%). An islet mass of 2000 IEQ, high islet purity, increased recipient body weight, and high islet pellet volume increased the likelihood of successful reversal of diabetes in transplanted mice. Also, higher insulin secretory status of islets at basal stimulus was associated with a reduced mouse cure rate. The cumulative incidence of graft failure was significantly greater in human islets (56.12%) compared with porcine islets 35.57% (P ≤ .001). Conclusion Factors affecting NM bioassay were identified (islet mass, islet purity, pellet size, in vitro insulin secretory capability and mouse recipient body weight) and should be considered when evaluating islet function. PMID:23677052

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Negative core affect and employee silence: How differences in activation, cognitive rumination, and problem-solving demands matter.

PubMed

Madrid, Hector P; Patterson, Malcolm G; Leiva, Pedro I

2015-11-01

Employees can help to improve organizational performance by sharing ideas, suggestions, or concerns about practices, but sometimes they keep silent because of the experience of negative affect. Drawing and expanding on this stream of research, this article builds a theoretical rationale based on core affect and cognitive appraisal theories to describe how differences in affect activation and boundary conditions associated with cognitive rumination and cognitive problem-solving demands can explain employee silence. Results of a diary study conducted with professionals from diverse organizations indicated that within-person low-activated negative core affect increased employee silence when, as an invariant factor, cognitive rumination was high. Furthermore, within-person high-activated negative core affect decreased employee silence when, as an invariant factor, cognitive problem-solving demand was high. Thus, organizations should manage conditions to reduce experiences of low-activated negative core affect because these feelings increase silence in individuals high in rumination. In turn, effective management of experiences of high-activated negative core affect can reduce silence for individuals working under high problem-solving demand situations. (c) 2015 APA, all rights reserved).

Substituting Tyr138 in the active site loop of human phenylalanine hydroxylase affects catalysis and substrate activation.

PubMed

Leandro, João; Stokka, Anne J; Teigen, Knut; Andersen, Ole A; Flatmark, Torgeir

2017-07-01

Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Biochemical and biophysical work has demonstrated that it cycles between two states with a variably low and a high activity, and that the substrate l-Phe is the key player in this transition. X-ray structures of the catalytic domain have shown mobility of a partially intrinsically disordered Tyr 138 -loop to the active site in the presence of l-Phe. The mechanism by which the loop dynamics are coupled to substrate binding at the active site in tetrameric PAH is not fully understood. We have here conducted functional studies of four Tyr 138 point mutants. A high linear correlation ( r 2 = 0.99) was observed between their effects on the catalytic efficiency of the catalytic domain dimers and the corresponding effect on the catalytic efficiency of substrate-activated full-length tetramers. In the tetramers, a correlation ( r 2 = 0.96) was also observed between the increase in catalytic efficiency (activation) and the global conformational change (surface plasmon resonance signal response) at the same l-Phe concentration. The new data support a similar functional importance of the Tyr 138 -loop in the catalytic domain and the full-length enzyme homotetramer.

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. © 2015 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Neuropeptides activate human mast cell degranulation and chemokine production

PubMed Central

Kulka, Marianna; Sheen, Cecilia H; Tancowny, Brian P; Grammer, Leslie C; Schleimer, Robert P

2008-01-01

During neuronal-induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcεRI-independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti-IgE and compound 48/80. Primary cultured mast cells, generated from CD34+ progenitors in the presence of stem cell factor and interleukin-6 (IL-6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti-IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein-1, inducible protein-10, monokine induced by interferon-γ (MIG), RANTES (regulated on activation, normal, T-cell expressed, and secreted) and IL-8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL-3 and granulocyte–macrophage colony-stimulating factor, but not IL-4, interferon-γ or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti-IgE up-regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G-protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases. PMID

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... (Obligation To Report Factors Affecting Entitlement) Activity; Comment Request AGENCY: Veterans Benefits... 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 of...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... (Obligation to Report Factors Affecting Entitlement) Activity: Comment Request AGENCY: Veterans Benefits... 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 of...

Neural evidence that human emotions share core affective properties.

PubMed

Wilson-Mendenhall, Christine D; Barrett, Lisa Feldman; Barsalou, Lawrence W

2013-06-01

Research on the "emotional brain" remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect--a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena.

Neural Evidence that Human Emotions Share Core Affective Properties

PubMed Central

Wilson-Mendenhall, Christine D.; Barrett, Lisa Feldman; Barsalou, Lawrence W.

2014-01-01

Research on the “emotional brain” remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect – a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena. PMID:23603916

Towards discrete wavelet transform-based human activity recognition

NASA Astrophysics Data System (ADS)

Khare, Manish; Jeon, Moongu

2017-06-01

Providing accurate recognition of human activities is a challenging problem for visual surveillance applications. In this paper, we present a simple and efficient algorithm for human activity recognition based on a wavelet transform. We adopt discrete wavelet transform (DWT) coefficients as a feature of human objects to obtain advantages of its multiresolution approach. The proposed method is tested on multiple levels of DWT. Experiments are carried out on different standard action datasets including KTH and i3D Post. The proposed method is compared with other state-of-the-art methods in terms of different quantitative performance measures. The proposed method is found to have better recognition accuracy in comparison to the state-of-the-art methods.

Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt.

PubMed

Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirano; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2013-01-01

Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect.

Brain activation during human male ejaculation revisited.

PubMed

Georgiadis, Janniko R; Reinders, A A T Simone; Van der Graaf, Ferdinand H C E; Paans, Anne M J; Kortekaas, Rudie

2007-04-16

In a prior [O]-H2O positron emission tomographic study we reported brain regions involved in human male ejaculation. Here, we used another, more recently acquired data set to evaluate the methodological approach of this previous study, and discovered that part of the reported activation pattern was not related to ejaculation. With a new analysis of these ejaculation data, we now demonstrate ejaculation-related activations in the deep cerebellar nuclei (dentate nucleus), anterior vermis, pons, and ventrolateral thalamus, and, most importantly, ejaculation-related deactivations throughout the prefrontal cortex. This revision offers a new and more accurate insight into the brain regions involved in human male ejaculation.

Predicting human activities in sequences of actions in RGB-D videos

NASA Astrophysics Data System (ADS)

Jardim, David; Nunes, Luís.; Dias, Miguel

2017-03-01

In our daily activities we perform prediction or anticipation when interacting with other humans or with objects. Prediction of human activity made by computers has several potential applications: surveillance systems, human computer interfaces, sports video analysis, human-robot-collaboration, games and health-care. We propose a system capable of recognizing and predicting human actions using supervised classifiers trained with automatically labeled data evaluated in our human activity RGB-D dataset (recorded with a Kinect sensor) and using only the position of the main skeleton joints to extract features. Using conditional random fields (CRFs) to model the sequential nature of actions in a sequence has been used before, but where other approaches try to predict an outcome or anticipate ahead in time (seconds), we try to predict what will be the next action of a subject. Our results show an activity prediction accuracy of 89.9% using an automatically labeled dataset.

Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans.

PubMed

Reinisch, June M; Mortensen, Erik Lykke; Sanders, Stephanie A

2017-07-01

Prenatal sex hormone levels affect physical and behavioral sexual differentiation in animals and humans. Although prenatal hormones are theorized to influence sexual orientation in humans, evidence is sparse. Sexual orientation variables for 34 prenatally progesterone-exposed subjects (17 males and 17 females) were compared to matched controls (M age = 23.2 years). A case-control double-blind design was used drawing on existing data from the US/Denmark Prenatal Development Project. Index cases were exposed to lutocyclin (bioidentical progesterone = C 21 H 30 O 2 ; M W : 314.46) and no other hormonal preparation. Controls were matched on 14 physical, medical, and socioeconomic variables. A structured interview conducted by a psychologist and self-administered questionnaires were used to collect data on sexual orientation, self-identification, attraction to the same and other sex, and history of sexual behavior with each sex. Compared to the unexposed, fewer exposed males and females identified as heterosexual and more of them reported histories of same-sex sexual behavior, attraction to the same or both sexes, and scored higher on attraction to males. Measures of heterosexual behavior and scores on attraction to females did not differ significantly by exposure. We conclude that, regardless of sex, exposure appeared to be associated with higher rates of bisexuality. Prenatal progesterone may be an underappreciated epigenetic factor in human sexual and psychosexual development and, in light of the current prevalence of progesterone treatment during pregnancy for a variety of pregnancy complications, warrants further investigation. These data on the effects of prenatal exposure to exogenous progesterone also suggest a potential role for natural early perturbations in progesterone levels in the development of sexual orientation.

HCG-Activated Human Peripheral Blood Mononuclear Cells (PBMC) Promote Trophoblast Cell Invasion

PubMed Central

Wang, Yaqin; Guo, Yue; Zhou, Danni; Xu, Mei; Ding, Jinli; Yang, Jing

2015-01-01

Successful embryo implantation and placentation depend on appropriate trophoblast invasion into the maternal endometrial stroma. Human chorionic gonadotropin (hCG) is one of the earliest embryo-derived secreted signals in the peripheral blood mononuclear cells (PBMC) that abundantly expresses hCG receptors. The aims of this study were to estimate the effect of human embryo–secreted hCG on PBMC function and investigate the role and underlying mechanisms of activated PBMC in trophoblast invasion. Blood samples were collected from women undergoing benign gynecological surgery during the mid-secretory phase. PBMC were isolated and stimulated with or without hCG for 0 or 24 h. Interleukin-1β (IL-1β) and leukemia inhibitory factor (LIF) expressions in PBMC were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR). The JAR cell line served as a model for trophoblast cells and was divided into four groups: control, hCG only, PBMC only, and PBMC with hCG. JAR cell invasive and proliferative abilities were detected by trans-well and CCK8 assays and matrix metalloproteinase (MMP)-2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 expressions in JAR cells were detected by western blotting and real-time PCR analysis. We found that hCG can remarkably promote IL-1β and LIF promotion in PBMC after 24-h culture. PBMC activated by hCG significantly increased the number of invasive JAR cells in an invasion assay without affecting proliferation, and hCG-activated PBMC significantly increased MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expressions in JAR cells in a dose-dependent manner. This study demonstrated that hCG stimulates cytokine secretion in human PBMC and could stimulate trophoblast invasion. PMID:26087261

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,…

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…

Activity of the Human Rhinovirus 3C Protease Studied in Various Buffers, Additives and Detergents Solutions for Recombinant Protein Production

PubMed Central

Tufail, Soban; Ismat, Fouzia; Imran, Muhammad; Iqbal, Mazhar; Mirza, Osman; Rhaman, Moazur

2016-01-01

Proteases are widely used to remove affinity and solubility tags from recombinant proteins to avoid potential interference of these tags with the structure and function of the fusion partner. In recent years, great interest has been seen in use of the human rhinovirus 3C protease owing to its stringent sequence specificity and enhanced activity. Like other proteases, activity of the human rhinovirus 3C protease can be affected in part by the buffer components and additives that are generally employed for purification and stabilization of proteins, hence, necessitate their removal by tedious and time-consuming procedures before proteolysis can occur. To address this issue, we examined the effect of elution buffers used for common affinity based purifications, salt ions, stability/solubility and reducing agents, and detergents on the activity of the human rhinovirus 3C protease using three different fusion proteins at 4°C, a temperature of choice for purification of many proteins. The results show that the human rhinovirus 3C protease performs better at 4°C than the frequently used tobacco etch virus protease and its activity was insensitive to most of the experimental conditions tested. Though number of fusion proteins tested is limited, we expect that these finding will facilitate the use of the human rhinovirus 3C protease in recombinant protein production for pharmaceutical and biotechnological applications. PMID:27093053

Activity of the Human Rhinovirus 3C Protease Studied in Various Buffers, Additives and Detergents Solutions for Recombinant Protein Production.

PubMed

Ullah, Raheem; Shah, Majid Ali; Tufail, Soban; Ismat, Fouzia; Imran, Muhammad; Iqbal, Mazhar; Mirza, Osman; Rhaman, Moazur

2016-01-01

Proteases are widely used to remove affinity and solubility tags from recombinant proteins to avoid potential interference of these tags with the structure and function of the fusion partner. In recent years, great interest has been seen in use of the human rhinovirus 3C protease owing to its stringent sequence specificity and enhanced activity. Like other proteases, activity of the human rhinovirus 3C protease can be affected in part by the buffer components and additives that are generally employed for purification and stabilization of proteins, hence, necessitate their removal by tedious and time-consuming procedures before proteolysis can occur. To address this issue, we examined the effect of elution buffers used for common affinity based purifications, salt ions, stability/solubility and reducing agents, and detergents on the activity of the human rhinovirus 3C protease using three different fusion proteins at 4°C, a temperature of choice for purification of many proteins. The results show that the human rhinovirus 3C protease performs better at 4°C than the frequently used tobacco etch virus protease and its activity was insensitive to most of the experimental conditions tested. Though number of fusion proteins tested is limited, we expect that these finding will facilitate the use of the human rhinovirus 3C protease in recombinant protein production for pharmaceutical and biotechnological applications.

Low Oxygen Tension Enhances Expression of Myogenic Genes When Human Myoblasts Are Activated from G0 Arrest

PubMed Central

Sellathurai, Jeeva; Nielsen, Joachim; Hejbøl, Eva Kildall; Jørgensen, Louise Helskov; Dhawan, Jyotsna; Nielsen, Michael Friberg Bruun; Schrøder, Henrik Daa

2016-01-01

Objectives Most cell culture studies have been performed at atmospheric oxygen tension of 21%, however the physiological oxygen tension is much lower and is a factor that may affect skeletal muscle myoblasts. In this study we have compared activation of G0 arrested myoblasts in 21% O2 and in 1% O2 in order to see how oxygen tension affects activation and proliferation of human myoblasts. Materials and Methods Human myoblasts were isolated from skeletal muscle tissue and G0 arrested in vitro followed by reactivation at 21% O2 and 1% O2. The effect was assesses by Real-time RT-PCR, immunocytochemistry and western blot. Results and Conclusions We found an increase in proliferation rate of myoblasts when activated at a low oxygen tension (1% O2) compared to 21% O2. In addition, the gene expression studies showed up regulation of the myogenesis related genes PAX3, PAX7, MYOD, MYOG (myogenin), MET, NCAM, DES (desmin), MEF2A, MEF2C and CDH15 (M-cadherin), however, the fraction of DES and MYOD positive cells was not increased by low oxygen tension, indicating that 1% O2 may not have a functional effect on the myogenic response. Furthermore, the expression of genes involved in the TGFβ, Notch and Wnt signaling pathways were also up regulated in low oxygen tension. The differences in gene expression were most pronounced at day one after activation from G0-arrest, thus the initial activation of myoblasts seemed most sensitive to changes in oxygen tension. Protein expression of HES1 and β-catenin indicated that notch signaling may be induced in 21% O2, while the canonical Wnt signaling may be induced in 1% O2 during activation and proliferation of myoblasts. PMID:27442119

Probiotic Lactobacillus Strains Stimulate the Inflammatory Response and Activate Human Macrophages.

PubMed

Rocha-Ramírez, L M; Pérez-Solano, R A; Castañón-Alonso, S L; Moreno Guerrero, S S; Ramírez Pacheco, A; García Garibay, M; Eslava, C

2017-01-01

Lactobacilli have been shown to promote health functions. In this study, we analyzed the mechanism by which four different strains of probiotics affected innate immunity, such as regulation of ROS, cytokines, phagocytosis, bactericidal activity, signaling by NF- κ B pp65, and TLR2 activation. The production of ROS was dependent on the concentration and species of Lactobacillus . The results obtained from the tested strains ( Lactobacillus rhamnosus GG, L. rhamnosus KLSD, L. helveticus IMAU70129, and L. casei IMAU60214) showed that strains induced early proinflammatory cytokines such as IL-8,TNF- α , IL-12p70, and IL-6. However, IL-1 β expression was induced only by L. helveticus and L. casei strains (after 24 h stimulation). Phagocytosis and bactericidal activity of macrophages against various pathogens, such as S. aureus , S. typhimurium , and E. coli , were increased by pretreatment with Lactobacillus . The nuclear translocation NF- κ B pp65 and TLR2-dependent signaling were also increased by treatment with the probiotics. Taken together, the experiments demonstrate that probiotic strains of Lactobacillus exert early immunostimulatory effects that may be directly linked to the initial inflammation of the response of human macrophages.

Probiotic Lactobacillus Strains Stimulate the Inflammatory Response and Activate Human Macrophages

PubMed Central

Moreno Guerrero, S. S.; Ramírez Pacheco, A.; García Garibay, M.; Eslava, C.

2017-01-01

Lactobacilli have been shown to promote health functions. In this study, we analyzed the mechanism by which four different strains of probiotics affected innate immunity, such as regulation of ROS, cytokines, phagocytosis, bactericidal activity, signaling by NF-κB pp65, and TLR2 activation. The production of ROS was dependent on the concentration and species of Lactobacillus. The results obtained from the tested strains (Lactobacillus rhamnosus GG, L. rhamnosus KLSD, L. helveticus IMAU70129, and L. casei IMAU60214) showed that strains induced early proinflammatory cytokines such as IL-8,TNF-α, IL-12p70, and IL-6. However, IL-1β expression was induced only by L. helveticus and L. casei strains (after 24 h stimulation). Phagocytosis and bactericidal activity of macrophages against various pathogens, such as S. aureus, S. typhimurium, and E. coli, were increased by pretreatment with Lactobacillus. The nuclear translocation NF-κB pp65 and TLR2-dependent signaling were also increased by treatment with the probiotics. Taken together, the experiments demonstrate that probiotic strains of Lactobacillus exert early immunostimulatory effects that may be directly linked to the initial inflammation of the response of human macrophages. PMID:28758133

Anti-inflammatory activity of fisetin in human gingival fibroblasts treated with lipopolysaccharide.

PubMed

Gutiérrez-Venegas, Gloria; Contreras-Sánchez, Anabel; Ventura-Arroyo, Jairo Agustín

2014-10-01

Fisetin is an anti-inflammatory flavonoid; however, its anti-inflammatory mechanism is not yet understood. In this study, we evaluated the anti-inflammatory effect of fisetin and its association with mitogen-activated protein kinase (MAPK) and nuclear factor kappa-beta pathways in human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) obtained from Porphyromonas gingivalis. The cell signaling, cell viability, and cyclooxygenase-2 (COX-2) expression of HGFs treated with various concentrations (0, 1, 5, 10, and 15 μM) of fisetin were measured by cell viability assay (MTT), Western blotting, and reverse transcriptase polymerase chain reaction analysis on COX-2. We found that fisetin significantly reduced the synthesis and expression of prostaglandin E2 in HGFs treated with LPS. Activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK was suppressed consistently by fisetin in HGFs treated with LPS. The data indicate that fisetin inhibits MAPK activation and COX-2 expression without affecting cell viability. These findings may be valuable for understanding the mechanism of the effect of fisetin on periodontal disease.

Regulated expression of telomerase activity in human T lymphocyte development and activation

PubMed Central

1996-01-01

Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of S pi protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion. PMID:8676067

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0733] Guidance for Industry on Evaluating the Safety of Flood-Affected Food Crops for Human Consumption; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

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. © 2016 Wiley Periodicals, Inc.

Human infant faces provoke implicit positive affective responses in parents and non-parents alike.

PubMed

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.

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

Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities.

PubMed

Piwetz, Sarah; Lundquist, David; Würsig, Bernd

2015-01-01

Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts. © 2015 Elsevier Ltd All rights reserved.