WorldWideScience

Sample records for human thermophysiological responses

  1. Thermal sensation and thermophysiological responses with metabolic step-changes

    DEFF Research Database (Denmark)

    Goto, Tomonobu; Toftum, Jørn; deDear, Richard

    2006-01-01

    This study investigated the effect on thermal perception and thermophysiological variables of controlled metabolic excursions of various intensities and durations. Twenty-four subjects alternately were seated on a chair or exercised by walking on a treadmill at a temperature predicted to be neutral...... at sedentary activity. In a second experimental series, subjects alternated between rest and exercise as well as between exercise at different intensities at two temperature levels. Measurements comprised skin and oesophageal temperatures, heart rate and subjective responses. Thermal sensation started to rise....... The sensitivity of thermal sensation to changes in core temperature was higher for activity down-steps than for up-steps. A model was proposed that estimates transient thermal sensation after metabolic step-changes. Based on predictions by the model, weighting factors were suggested to estimate a representative...

  2. An Exercise Health Simulation Method Based on Integrated Human Thermophysiological Model

    Directory of Open Access Journals (Sweden)

    Nan Jia

    2017-01-01

    Full Text Available Research of healthy exercise has garnered a keen research for the past few years. It is known that participation in a regular exercise program can help improve various aspects of cardiovascular function and reduce the risk of suffering from illness. But some exercise accidents like dehydration, exertional heatstroke, and even sudden death need to be brought to attention. If these exercise accidents can be analyzed and predicted before they happened, it will be beneficial to alleviate or avoid disease or mortality. To achieve this objective, an exercise health simulation approach is proposed, in which an integrated human thermophysiological model consisting of human thermal regulation model and a nonlinear heart rate regulation model is reported. The human thermoregulatory mechanism as well as the heart rate response mechanism during exercise can be simulated. On the basis of the simulated physiological indicators, a fuzzy finite state machine is constructed to obtain the possible health transition sequence and predict the exercise health status. The experiment results show that our integrated exercise thermophysiological model can numerically simulate the thermal and physiological processes of the human body during exercise and the predicted exercise health transition sequence from finite state machine can be used in healthcare.

  3. Thermophysiological responses and work strain in fishermen on deep-sea fishing vessels.

    Science.gov (United States)

    Høye, Erik Ulvolden; Sandsund, Mariann; Heidelberg, Cecilie Thon; Aasmoe, Lisbeth; Reinertsen, Randi Eidsmo

    2016-01-01

    Fishermen working on deep-sea vessels in the Barents and Norwegian Sea are exposed to low air temperatures, strong winds, high humidity, rain, snow and work at different intensities. Few studies have investigated the effect of environmental work factors on the physiology of this occupational group. The aim of the study was to investigate work strain and thermophysiological responses of fishermen on the trawl and factory decks of deep-sea vessels. Twenty-five professional male fishermen (age 39 ± 13 years) were recruited to the study which was performed on three trawlers in the Norwegian Sea in April, June and August 2014. During a six-hour shift, heart rate (HR), core (Tc) and mean skin (Ts) temperatures were recorded, and questions about subjective thermal sensation and comfort were answered. Short periods of hard (above 86% of HRmax) work raised Tc by 0.8°C to 37.8°C and decreased Ts by 2.3°C to 29.8°C during work on the trawl deck, and subjects reported being warm and sweaty. On the factory deck long periods of fairly light (between 52% and 66% HRmax) work, Tc of 37.4°C and Ts of 30.9°C were measured. Fishermen experience intermittent periods of heavy work on the trawl deck shown with elevated core temperature and HR. Work on the factory deck includes long periods of repetitive work with light to moderate work strain. A better understanding of work strain and environmental challenges during work on Norwegian deep-sea vessels will help identify exposure risks during work in the cold and heat.

  4. Comparison of Biophysical Characteristics and Predicted Thermophysiological Responses of Three Prototype Body Armor Systems Versus Baseline U.S. Army Body Armor Systems

    Science.gov (United States)

    2015-06-19

    TECHNICAL REPORT NO. T15-6 DATE June 2015 ADA COMPARISON OF BIOPHYSICAL CHARACTERISTICS AND...USARIEM TECHNICAL REPORT T15-6 COMPARISON OF BIOPHYSICAL CHARACTERISTICS AND PREDICTED THERMOPHYSIOLOGICAL RESPONSES OF THREE... Biophysics and Biomedical Modeling Division June 2015 U.S. Army Research Institute of Environmental Medicine Natick, MA 01760-5007

  5. Thermo-Physiological Responses of Sailors in a Disabled Submarine with Interior Cabin Temperature and Humidity Slowly Rising as Predicted by Computer Simulation Techniques

    Science.gov (United States)

    2013-09-01

    modeling; disabled submarine; DISSUB; thermoregulation Unclassified Unclassified Unclassified Unclassified 58 Adam W. Potter 508-233-4735 Reset iii...has been the threat of hypothermia from the environment caused by cold ocean water while waiting the sub’s rescue (Castellani et al., 2005...the SCENARIO thermo-physiological model developed at USARIEM by Kraning and Gonzalez (1997) (Fig 1). It is a rational human thermoregulation model

  6. Thermal conditions in freezing chambers and prediction of the thermophysiological responses of workers

    Science.gov (United States)

    Raimundo, A. M.; Oliveira, A. V. M.; Gaspar, A. R.; Quintela, D. A.

    2015-11-01

    The present work is dedicated to the assessment of the cold thermal strain of human beings working within freezing chambers. To obtain the present results, both field measurements and a numerical procedure based on a modified version of the Stolwijk thermoregulation model were used. Eighteen freezing chambers were considered. A wide range of physical parameters of the cold stores, the workers clothing insulation, and the working and recovering periods were observed. The combination of these environmental and individual parameters lead to different levels of thermal stress, which were grouped under three categories. Some good practices were observed in the field evaluations, namely situations with appropriate level of clothing protection and limited duration of exposure to cold avoiding unacceptable level of hypothermia. However, the clothing ensembles normally used by the workers do not provide the minimum required insulation, which suggests the possibility of the whole body cooling for levels higher than admissible. The numerical predictions corroborate the main conclusions of the field survey. The results obtained with both methodologies clearly show that, for the low temperature of the freezing chambers, the clothing insulation is insufficient, the exposure periods are too long, and the recovering periods are inadequate. Thus, high levels of physiological strain can indeed be reached by human beings under such working environments.

  7. A Novel Exercise Thermophysiology Comfort Prediction Model with Fuzzy Logic

    Directory of Open Access Journals (Sweden)

    Nan Jia

    2016-01-01

    Full Text Available Participation in a regular exercise program can improve health status and contribute to an increase in life expectancy. However, exercise accidents like dehydration, exertional heatstroke, syncope, and even sudden death exist. If these accidents can be analyzed or predicted before they happen, it will be beneficial to alleviate or avoid uncomfortable or unacceptable human disease. Therefore, an exercise thermophysiology comfort prediction model is needed. In this paper, coupling the thermal interactions among human body, clothing, and environment (HCE as well as the human body physiological properties, a human thermophysiology regulatory model is designed to enhance the human thermophysiology simulation in the HCE system. Some important thermal and physiological performances can be simulated. According to the simulation results, a human exercise thermophysiology comfort prediction method based on fuzzy inference system is proposed. The experiment results show that there is the same prediction trend between the experiment result and simulation result about thermophysiology comfort. At last, a mobile application platform for human exercise comfort prediction is designed and implemented.

  8. How to measure thermal effects of personal cooling systems : Human, thermal manikin and human simulator study

    NARCIS (Netherlands)

    Bogerd, N.; Psikuta, A.; Daanen, H.A.M.; Rossi, R.M.

    2010-01-01

    Thermal effects, such as cooling power and thermophysiological responses initiated upon application of a personal cooling system, can be assessed with (i) humans, (ii) a thermal manikin and (iii) a thermophysiological human simulator. In order to compare these methods, a cooling shirt (mild cooling)

  9. Validation of the thermophysiological model by Fiala for prediction of local skin temperatures

    Science.gov (United States)

    Martínez, Natividad; Psikuta, Agnes; Kuklane, Kalev; Quesada, José Ignacio Priego; de Anda, Rosa María Cibrián Ortiz; Soriano, Pedro Pérez; Palmer, Rosario Salvador; Corberán, José Miguel; Rossi, René Michel; Annaheim, Simon

    2016-12-01

    The most complete and realistic physiological data are derived from direct measurements during human experiments; however, they present some limitations such as ethical concerns, time and cost burden. Thermophysiological models are able to predict human thermal response in a wide range of environmental conditions, but their use is limited due to lack of validation. The aim of this work was to validate the thermophysiological model by Fiala for prediction of local skin temperatures against a dedicated database containing 43 different human experiments representing a wide range of conditions. The validation was conducted based on root-mean-square deviation (rmsd) and bias. The thermophysiological model by Fiala showed a good precision when predicting core and mean skin temperature (rmsd 0.26 and 0.92 °C, respectively) and also local skin temperatures for most body sites (average rmsd for local skin temperatures 1.32 °C). However, an increased deviation of the predictions was observed for the forehead skin temperature (rmsd of 1.63 °C) and for the thigh during exercising exposures (rmsd of 1.41 °C). Possible reasons for the observed deviations are lack of information on measurement circumstances (hair, head coverage interference) or an overestimation of the sweat evaporative cooling capacity for the head and thigh, respectively. This work has highlighted the importance of collecting details about the clothing worn and how and where the sensors were attached to the skin for achieving more precise results in the simulations.

  10. Hair coat characteristics and thermophysiological stress response of Nguni and Boran cows raised under hot environmental conditions

    Science.gov (United States)

    Katiyatiya, C. L. F.; Muchenje, V.

    2017-08-01

    Breed, age, coat colour, month and temperature humidity index (THI) influence on body weight (W), body condition score (BCS), thermophysiological variables (rectal temperature (Tr), skin temperature (Tsk)) and hair length was studied in Nguni (n = 19) and Boran (n = 16). As a result of this study, breed influenced W, BCS and Tsk on the neck and belly (P white-black Boran cows had increased BCS. Nguni cows with red, fawn and white cows had high BCS. Fawn-coloured Nguni cows and white-brown Boran cows had the more weight than cows with other colours compared in the study. White-red Nguni and Boran cows recorded the highest Tr. For Nguni cows, neck and belly temperatures were significantly (P < 0.001) correlated to thurl temperature. Boran cows had significant (P < 0.001) correlations for THI and neck, belly and thurl temperatures. The current study found that Nguni cows were more adapted to the prevailing bioclimatic changes. However, Boran cows have the potential of performing well under heat stress conditions over time.

  11. Can the PHS model (ISO7933) predict reasonable thermophysiological responses while wearing protective clothing in hot environments?

    Science.gov (United States)

    Wang, Faming; Kuklane, Kalev; Gao, Chuansi; Holmér, Ingvar

    2011-02-01

    In this paper, the prediction accuracy of the PHS (predicted heat strain) model on human physiological responses while wearing protective clothing ensembles was examined. Six human subjects (aged 29 ± 3 years) underwent three experimental trials in three different protective garments (clothing thermal insulation I(cl) ranges from 0.63 to 2.01 clo) in two hot environments (40 °C, relative humidities: 30% and 45%). The observed and predicted mean skin temperature, core body temperature and sweat rate were presented and statistically compared. A significant difference was found in the metabolic rate between FIRE (firefighting clothing) and HV (high visibility clothing) or MIL (military clothing) (p thermal insulations above 1.0 clo. The results showed that the PHS model generated unreliable predictions on body core temperature when human subjects wore thick protective clothing such as firefighting clothing (I(cl) > 1.0 clo). The predicted mean skin temperatures in three clothing ensembles HV, MIL and FIRE were also outside the expected limits. Thus, there is a need for further extension for the clothing insulation validation range of the PHS model. It is recommended that the PHS model should be amended and validated by individual algorithms, physical or physiological parameters, and further subject studies.

  12. Integration of thermophysiological body model in CFD

    Science.gov (United States)

    Pichurov, George; Stankov, Peter

    2013-09-01

    A two-node mathematical model of the human thermophysiological system has been integrated into a Computational Fluid Dynamic (CFD) simulation of the airflow in a room. Temperature inputs from the CFD are used by the model to evaluate the dry and latent heat flux from the body surface and output them as boundary conditions. This is an iterative process and convergence is ensured by under-relaxation of the latent heat flux. The model also considers the dry and latent heat resistance of clothing. Numerical predictions of the body heat loss and airflow are compared against physical measurements in a climate chamber. Good agreement was observed when using the low Reynolds number turbulence model. The integrated simulation performs well under wide set of conditions, predicting body core and skin temperature, blood flow, skin wittedness, as well as the transfer of heat and moisture released by the body into the room.

  13. Multi-sector thermo-physiological head simulator for headgear research

    Science.gov (United States)

    Martinez, Natividad; Psikuta, Agnes; Corberán, José Miguel; Rossi, René M.; Annaheim, Simon

    2017-02-01

    A novel thermo-physiological human head simulator for headgear testing was developed by coupling a thermal head manikin with a thermo-physiological model. As the heat flux at head-site is directly measured by the head manikin, this method provides a realistic quantification of the heat transfer phenomena occurring in the headgear, such as moisture absorption-desorption cycles, condensation, or moisture migration across clothing layers. Before coupling, the opportunities of the head manikin for representing the human physiology were evaluated separately. The evaluation revealed reduced precision in forehead and face temperature predictions under extreme heterogeneous temperature distributions and no initial limitation for simulating temperature changes observed in the human physiology. The thermo-physiological model predicted higher sweat rates when applied for coupled than for pure virtual simulations. After coupling, the thermo-physiological human head simulator was validated using eight human experiments. It precisely predicted core, mean skin, and forehead temperatures with average rmsd values within the average experimental standard deviation (rmsd of 0.20 ± 0.15, 0.83 ± 0.34, and 1.04 ± 0.54 °C, respectively). However, in case of forehead, precision was lower for the exposures including activity than for the sedentary exposures. The representation of the human sweat evaporation could be affected by a reduced evaporation efficiency and the manikin sweat dynamics. The industry will benefit from this thermo-physiological human head simulator leading to the development of helmet designs with enhanced thermal comfort and, therefore, with higher acceptance by users.

  14. A Comparative thermophysiological study in sport bras for running

    Science.gov (United States)

    Carneiro, L. P.; Miranda, T. M. R.; Catarino, A.

    2017-10-01

    Comfort in clothing is essential for user’s performance and is considered as a quality factor when choosing a particular piece of garment. Sportswear’s need include comfort and functionality, meaning that the thermo-physiological properties are of extreme importance. The aim of this work consists in comparing six different models of sports bra used specifically for running, taking into consideration the aspects of the thermo-physiological properties, air permeability, moisture behaviour, and friction. This paper is part of an ongoing research aiming to establish a comprehension about function and comfort characteristics for sport bras and propose a new bra with improved characteristics both in ergonomics design as well as in comfort performance. The thermal characterization of different regions on each bra were tested using Alambeta apparatus, Textest FX 3300 for air permeability and Frictorq for friction. Evaporation tests were also carried out in different regions on each bra at 37ºC corresponding to internal temperature of the human body. The results show that raw material, structures and construction can have influence in the properties studied.

  15. Evaluating thermophysiological comfort using the principles of sensory analysis.

    Science.gov (United States)

    Cubrić, Ivana Salopek; Skenderi, Zenun

    2013-03-01

    Thermophysiological comfort applies to the way in which clothing lets through or retains heat and moisture and helps the body retain heat balance in rest position or at various levels of activities. In this paper, the principles of sensory analysis are used to define the protocol of new method for the evaluation of thermophysiological comfort wearing different garments. Sensory analysis was chosen because as a scientific discipline that applies experiment principles using human senses is used for the evaluation of consumer goods. Test protocol using assessors described in this paper consists of the following steps: defining the interview content, finding potential assessors and making an interview, creating a survey, conducting a survey, group discussion, test and group discussion scoring, selection of assessors, assessment preparation and subjective assessment. On average the most distinctive increase in the sensation of warmth was recorded for the polyester clothing ensemble, and the lowest one for the cotton clothing ensemble. Concerning the average grades of comfort given by assesors, the most comfortable clothing ensemble is the one made of viscose. It was also found out that the method is especially suitable if a representative group of assessors is formed.

  16. Thermophysiologic aspects of the three-process-model of sleepiness regulation.

    Science.gov (United States)

    Kräuchi, Kurt; Cajochen, Christian; Wirz-Justice, Anna

    2005-04-01

    The following overview reconsiders the three-process model of sleepiness regulation (homeostatic, circadian, and sleep inertia) from a thermophysiologic point of view. Our results gathered over the last decade indicate that the homeostatic aspect of sleepiness regulation (ie, buildup of sleepiness during wakefulness and its decay during sleep) is not related to the thermoregulatory system, whereas the two other processes of sleepiness regulation (ie, circadian and sleep inertia process) are clearly related to thermoregulation in humans. Distal skin temperature of hands and feet seems to be the crucial variable for the association between thermophysiology, sleepiness, and sleep. Increased distal skin temperature before a nocturnal sleep episode is a good predictor for short sleep-onset latency. The disappearance of sleep inertia after sleep or a nap episode shows very similar kinetics as distal vasoconstriction. Furthermore, relaxation-induced sleepiness (eg, after lying down, at lights-off, with thermal biofeedback training) also evokes an increase in distal skin temperatures. The reverse effect occurs at lights-on or a posture change from supine to standing, Therefore, in terms of thermophysiology, sleep inertia can be explained as the reverse of a relaxation process (ie, decrease in distal skin temperatures). Our results reinterpret the so-called "sleep-evoked" reduction of core body temperature as a consequence of relaxation-induced vasodilatation after lights-off. Sleep per se has no further thermoregulatory effect. Taken together, a thermophysiologic approach may provide a successful strategy to treat sleep-onset insomnia and alleviate sleep inertia.

  17. Microbial barrier permeability and thermophysiological and mechanical properties of static dissipative woven fabric system

    Science.gov (United States)

    Schwarz, I.; Rogina-Car, B.; Kopitar, D.

    2017-10-01

    Some of the most significant properties of static dissipative woven fabric systems, in applications where contact of textile material and human body is present, beside antistatic properties are definitely microbial barrier permeability and thermophysiological properties. Application of such materials with associated properties is of great importance in bedding upholstery and comfortable apparel. Based on the conducted relevant tests, according to standardized and newly developed methods, it can be concluded that the such static dissipative woven fabric fulfils all the highly set criteria’s, resulting in a system that can, with certainty, provide the necessary health protection and comfort.

  18. Biothermal conditions on Mt. Zlatibor based on thermophysiological indices

    Directory of Open Access Journals (Sweden)

    Pecelj Milica

    2017-01-01

    Full Text Available This paper presents part of the research in the field of human bioclimatology and refers to biothermal conditions in different geographical environments in Serbia: an urban area and a mountain of medium height. The goal of the paper was to show bioclimatic differences during the summer between the city of Belgrade (116 m a.s.l. and the mountain resort of Zlatibor (1498 m a.s.l.. The basic principle of bioclimatic analysis is the human heat balance between man and environment. This methodological approach is a combination of physiological and meteorological parameters that result in thermophysiological bioclimatic indices: heat load (HL in man and the Universal Thermal Climate Index (UTCI. For this analysis, weather data for July, as the warmest month, was obtained, using daily meteorological data for the decade from 2000 to 2010. Results for July indicate a considerable difference between the two abovementioned environments. HL in Belgrade was dominated by degrees of comfort “hot” and “extremely hot, with the highest value of 4.540, while for Zlatibor the dominant degree of comfort was “warm”. The UTCI in Belgrade has dominated by strong heat stress and moderate heat stress, compared to Zlatibor where the UTCI is dominated by moderate heat stress. In addition, a significant part of the monitored decade on Mt. Zlatibor was without heat stress, with the exception of 2006 and 2007, indicating favorable biothermal characteristics. Therefore, compared to Belgrade, with its considerably lower overall heat stress Zlatibor has the characteristics of a site with favorable bioclimatic qualities.

  19. Influence of Phase-Change Materials on Thermo-Physiological Comfort in Warm Environment

    Directory of Open Access Journals (Sweden)

    Damjana Celcar

    2013-01-01

    Full Text Available The purpose of this research work is to investigate the influence of phase-change materials (PCMs on thermo-physiological comfort of different male business clothing systems evaluated in warm environment. The impact of particular business clothing on the thermo-physiological comfort of the wearer during different physical activity and environmental conditions (between 25°C and 10°C with step of 5°C, artificially created in a climate chamber, was determined experimentally, as a change of three physiological parameters of a human being: mean skin temperature, heart rate, and the amount of evaporated and condensed sweat. A questionnaire and an assessment scale were also used before, during, and after each experiment in order to evaluate the wearer’s subjective feeling of comfort. The results of the performed research work show that male business clothing systems in combination with PCMs do not affect the thermal-physiological comfort of the wearer in warm environment significantly, except at an ambient temperature of 15°C, where clothing systems in combination with PCMs produce a small heating effect. Furthermore, it was concluded that clothing systems in combination with PCMs indicate a small temporary thermal effect that is reflected in a slight rising or lowering of mean skin temperature during activity changes.

  20. Businesses’ human rights responsibilities

    Directory of Open Access Journals (Sweden)

    Corinne Lewis

    2012-12-01

    Full Text Available There is no international human rights law standard that expresslyprohibits businesses’ arbitrary displacement of persons. Businessesdo, however, have the responsibility to avoid infringements of humanrights that could lead to displacement and also to take actions toremedy their human rights violations that might lead to displacement.

  1. Probing human response times

    Science.gov (United States)

    Johansen, Anders

    2004-07-01

    In a recent preprint (Dialog in e-mail traffic, preprint cond-mat/0304433), the temporal dynamics of an e-mail network has been investigated by Eckmann, Moses and Sergi. Specifically, the time period between an e-mail message and its reply were recorded. It will be shown here that their data agrees quantitatively with the frame work proposed to explain a recent experiment on the response of “internauts” to a news publication (Physica A 296(3-4) (2001) 539) despite differences in communication channels, topics, time-scale and socio-economic characteristics of the two population. This suggest a generalized response time distribution ∼ t-1 for human populations in the absence of deadlines with important implications for psychological and social studies as well the study of dynamical networks.

  2. Transcompartmental Inflammatory Responses in Humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysacchar......OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following......-α, interleukin-6, and albumin (all p humans is followed by a transcompartmental proinflammatory response, the degree and differential...

  3. Isotopic ordering in eggshells reflects body temperatures and suggests differing thermophysiology in two Cretaceous dinosaurs.

    Science.gov (United States)

    Eagle, Robert A; Enriquez, Marcus; Grellet-Tinner, Gerald; Pérez-Huerta, Alberto; Hu, David; Tütken, Thomas; Montanari, Shaena; Loyd, Sean J; Ramirez, Pedro; Tripati, Aradhna K; Kohn, Matthew J; Cerling, Thure E; Chiappe, Luis M; Eiler, John M

    2015-10-13

    Our understanding of the evolutionary transitions leading to the modern endothermic state of birds and mammals is incomplete, partly because tools available to study the thermophysiology of extinct vertebrates are limited. Here we show that clumped isotope analysis of eggshells can be used to determine body temperatures of females during periods of ovulation. Late Cretaceous titanosaurid eggshells yield temperatures similar to large modern endotherms. In contrast, oviraptorid eggshells yield temperatures lower than most modern endotherms but ∼ 6 °C higher than co-occurring abiogenic carbonates, implying that this taxon did not have thermoregulation comparable to modern birds, but was able to elevate its body temperature above environmental temperatures. Therefore, we observe no strong evidence for end-member ectothermy or endothermy in the species examined. Body temperatures for these two species indicate that variable thermoregulation likely existed among the non-avian dinosaurs and that not all dinosaurs had body temperatures in the range of that seen in modern birds.

  4. Infants' Responses to Real Humans and Representations of Humans

    Science.gov (United States)

    Heron, Michelle; Slaughter, Virginia

    2010-01-01

    Infants' responses to typical and scrambled human body shapes were assessed in relation to the realism of the human body stimuli presented. In four separate experiments, infants were familiarized to typical human bodies and then shown a series of scrambled human bodies on the test. Looking behaviour was assessed in response to a range of different…

  5. Interaction of Alginate/Copper System on Cotton and Bamboo Fabrics: The Effect on Antimicrobial Activity and Thermophysiological Comfort Properties

    Directory of Open Access Journals (Sweden)

    Muhammet UZUN

    2013-09-01

    Full Text Available Antimicrobialagent treated materials have been widely used clinically as medical devices and articles, in which the active substances, such as antimicrobial molecules, are present on or in the matrix of the surface of the devices and articles.This study aims to treat a selection of fabrics with alginate/copper, and then determine the treated fabrics’antimicrobial activity against two common Gram-positive and Gram-negative bacteria. It is also aimed to analyse and evaluate the thermophysiological properties of the treated fabrics. Cotton, organic cotton and bamboo woven fabrics were employed. The fabrics were applied in 1 %, 3 % and 5 %w/v copper solutions andsubsequentlyspecimens were subjected to 10 min and 20 min ultrasonic energy treatment. The results clearly demonstrated that the cotton and organic cotton fabrics were successfully treatedwith the alginate/copper and the treated fabrics showed considerable zone of inhibitions. The bamboo fabric did not appear to bond effectively with the copper alginate, andas the result,the fabrics did not display any improved bacterial protection against the chosen bacteria. In fact the bamboo fabric lost its natural antimicrobialproperties after the alginate and copper treatment.The thermophysiological comfort properties of the treated cotton fabrics changed significantly; on the other hand, the treated bamboo fabrics were not affected by the copper treatment.  DOI: http://dx.doi.org/10.5755/j01.ms.19.3.1217

  6. Computational modeling of temperature elevation and thermoregulatory response in the brains of anesthetized rats locally exposed at 1.5 GHz

    Science.gov (United States)

    Hirata, Akimasa; Masuda, Hiroshi; Kanai, Yuya; Asai, Ryuichi; Fujiwara, Osamu; Arima, Takuji; Kawai, Hiroki; Watanabe, Soichi; Lagroye, Isabelle; Veyret, Bernard

    2011-12-01

    The dominant effect of human exposures to microwaves is caused by temperature elevation ('thermal effect'). In the safety guidelines/standards, the specific absorption rate averaged over a specific volume is used as a metric for human protection from localized exposure. Further investigation on the use of this metric is required, especially in terms of thermophysiology. The World Health Organization (2006 RF research agenda) has given high priority to research into the extent and consequences of microwave-induced temperature elevation in children. In this study, an electromagnetic-thermal computational code was developed to model electromagnetic power absorption and resulting temperature elevation leading to changes in active blood flow in response to localized 1.457 GHz exposure in rat heads. Both juvenile (4 week old) and young adult (8 week old) rats were considered. The computational code was validated against measurements for 4 and 8 week old rats. Our computational results suggest that the blood flow rate depends on both brain and core temperature elevations. No significant difference was observed between thermophysiological responses in 4 and 8 week old rats under these exposure conditions. The computational model developed herein is thus applicable to set exposure conditions for rats in laboratory investigations, as well as in planning treatment protocols in the thermal therapy.

  7. Oology and the evolution of thermophysiology in saurischian dinosaurs: homeotherm and endotherm deinonychosaurians?

    Directory of Open Access Journals (Sweden)

    Gerald Grellet-Tinner

    2006-01-01

    Full Text Available The origin of avian endothermy is a long-held question the answer of which cannot be provided by first level observations. Oological and reproductive characters have collectively provided a new source of data useful for phylogenetic analyses and paleobiological inferences. In addition, the observations of reproductive and oological evolutionary trends in saurischian dinosaurs lead to the interpretation that not only, the thermophysiology of these dinosaurs progressively became more avian-like but after re-examination allows to infer that deinonychosaurians represented here by three troodontids and one dromaeosaurid might already have developed an avian-like endothermy, thus predating the rise of avians. These results based on reproductive traits are independently corroborated by the discoveries of troodontid dinosaurs 1 in high latitudes, 2 covered with feathers in Chinese Lagerstätten, and recently 3 fossilized in a death pose identical to an avian sleeping posture.A origem da endotermia nas aves é uma questão há muito discutida e sua resposta não pode ser encontrada através de observações superficiais. Caracteres oológicos e reprodutivos surgiram como uma nova fonte de dados relevantes tanto para análises filogenéticas quanto para inferências paleobiológicas dos dinossauros Saurischia. Além disso, as observações das tendências evolutivas reprodutivas e oológicas nos dinossauros Saurischia nos levam a inferir que não apenas, como anteriormente a termofisiologia deste grupo de dinossauros tornou-se progressivamente ornítica, mas um posterior reexame nos permitiu concluir que os deinonicossauros, representados aqui por dois troodontídeos e um dromeossaurídeo, provavelmente já haviam desenvolvido uma endotermia semelhante a das aves, anterior, portanto, ao seu surgimento. Estes resultados baseados em características reprodutivas são independentemente corroborados pela descoberta dos dinossauros troodontídeos 1 em altas

  8. Multiphysics and Thermal Response Models to Improve Accuracy of Local Temperature Estimation in Rat Cortex under Microwave Exposure

    Directory of Open Access Journals (Sweden)

    Sachiko Kodera

    2017-03-01

    Full Text Available The rapid development of wireless technology has led to widespread concerns regarding adverse human health effects caused by exposure to electromagnetic fields. Temperature elevation in biological bodies is an important factor that can adversely affect health. A thermophysiological model is desired to quantify microwave (MW induced temperature elevations. In this study, parameters related to thermophysiological responses for MW exposures were estimated using an electromagnetic-thermodynamics simulation technique. To the authors’ knowledge, this is the first study in which parameters related to regional cerebral blood flow in a rat model were extracted at a high degree of accuracy through experimental measurements for localized MW exposure at frequencies exceeding 6 GHz. The findings indicate that the improved modeling parameters yield computed results that match well with the measured quantities during and after exposure in rats. It is expected that the computational model will be helpful in estimating the temperature elevation in the rat brain at multiple observation points (that are difficult to measure simultaneously and in explaining the physiological changes in the local cortex region.

  9. Humanity's Dual Response to Dogs and Wolves.

    Science.gov (United States)

    Treves, Adrian; Bonacic, Cristian

    2016-07-01

    Dogs were first domesticated 31 000-41 000 years ago. Humanity has experienced ecological costs and benefits from interactions with dogs and wolves. We propose that humans inherited a dual response of attraction or aversion that expresses itself independently to domestic and wild canids. The dual response has had far-reaching consequences for the ecology and evolution of all three taxa, including today's global 'ecological paw print' of 1 billion dogs and recent eradications of wolves. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. T-cell response in human leishmaniasis

    DEFF Research Database (Denmark)

    Kharazmi, A; Kemp, K; Ismail, A

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered...... from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  11. Corporate Social Responsibility and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2006-01-01

    rather than public regulation. The UN Global Compact and the UN Norms on human rights responsibilities for transnational and other corporations are discussed as examples of changes in international UN based regulation of corporations in relation to CSR topics, and as examples of network governance...

  12. Seasonality in human cognitive brain responses.

    Science.gov (United States)

    Meyer, Christelle; Muto, Vincenzo; Jaspar, Mathieu; Kussé, Caroline; Lambot, Erik; Chellappa, Sarah L; Degueldre, Christian; Balteau, Evelyne; Luxen, André; Middleton, Benita; Archer, Simon N; Collette, Fabienne; Dijk, Derk-Jan; Phillips, Christophe; Maquet, Pierre; Vandewalle, Gilles

    2016-03-15

    Daily variations in the environment have shaped life on Earth, with circadian cycles identified in most living organisms. Likewise, seasons correspond to annual environmental fluctuations to which organisms have adapted. However, little is known about seasonal variations in human brain physiology. We investigated annual rhythms of brain activity in a cross-sectional study of healthy young participants. They were maintained in an environment free of seasonal cues for 4.5 d, after which brain responses were assessed using functional magnetic resonance imaging (fMRI) while they performed two different cognitive tasks. Brain responses to both tasks varied significantly across seasons, but the phase of these annual rhythms was strikingly different, speaking for a complex impact of season on human brain function. For the sustained attention task, the maximum and minimum responses were located around summer and winter solstices, respectively, whereas for the working memory task, maximum and minimum responses were observed around autumn and spring equinoxes. These findings reveal previously unappreciated process-specific seasonality in human cognitive brain function that could contribute to intraindividual cognitive changes at specific times of year and changes in affective control in vulnerable populations.

  13. NASA Medical Response to Human Spacecraft Accidents

    Science.gov (United States)

    Patlach, Robert

    2011-01-01

    This slide presentation reviews NASA's role in the response to spacecraft accidents that involve human fatalities or injuries. Particular attention is given to the work of the Mishap Investigation Team (MIT), the first response to the accidents and the interface to the accident investigation board. The MIT does not investigate the accident, but the objective of the MIT is to gather, guard, preserve and document the evidence. The primary medical objectives of the MIT is to receive, analyze, identify, and transport human remains, provide assistance in the recovery effort, and to provide family Casualty Coordinators with latest recovery information. The MIT while it does not determine the cause of the accident, it acts as the fact gathering arm of the Mishap Investigation Board (MIB), which when it is activated may chose to continue to use the MIT as its field investigation resource. The MIT membership and the specific responsibilities and tasks of the flight surgeon is reviewed. The current law establishing the process is also reviewed.

  14. Delegating responsibilities in human-robot teams

    Science.gov (United States)

    DeKoven, Elyon A. M.; Bechtel, Bob; Zaientz, Jack; Lisse, Sean; Murphy, Anne K. G.

    2006-05-01

    Trends in combat technology research point to an increasing role for uninhabited vehicles and other robotic elements in modern warfare tactics. However, real-time control of multiple uninhabited battlefield robots and other semi-autonomous systems, in diverse fields of operation, is a difficult problem for modern warfighters that, while identified, has not been adequately addressed. Soar Technology is applying software agent technology to simplify demands on the human operator. Our goal is to build intelligent systems capable of finding the best balance of control between the human and autonomous system capabilities. We are developing an Intelligent Control Framework (ICF) from which to create agent-based systems that are able to dynamically delegate responsibilities across multiple robotic assets and the human operator. This paper describes proposed changes to our ICF architecture based on principles of human-machine teamwork derived from collaborative discourse theory. We outline the principles and the new architecture, and give examples of the benefits that can be realized from our approach.

  15. Human response to an individually controlled environment

    DEFF Research Database (Denmark)

    Knudsen, G.L.; Melikov, Arsen Krikor

    2005-01-01

    Forty-eight subjects tested an individually controlled system (ICS) at room air temperatures of 20, 22 and 26 degrees C. Human response to a reference condition without the ICS at a room air temperature of 22 degrees C was also collected. ne ICS incorporated Personalized Ventilation (PV), an under......-desk air terminal device supplying cool air, a chair with convectively heated backrest, an under-desk radiant heating panel and a floor-heating panel. The temperature of the PV air and the under-desk air was kept at 20 degrees C. The subjects were provided with control of the flow rate and direction...

  16. Cell Culture Assay for Human Noroviruses [response

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Tim M.; Honer Zu Bentrup, Kerstin; Orosz Coghlan, Patricia; Dohnalkova, Alice; Mayer, Brooke K.; Bartholomew, Rachel A.; Valdez, Catherine O.; Bruckner-Lea, Cindy J.; Gerba, Charles P.; Abbaszadegan, Morteza A.; Nickerson, Cheryl A.

    2007-07-01

    We appreciate the comments provided by Leung et al., in response to our recently published article “In Vitro Cell Culture Infectivity Assay for Human Noroviruses” by Straub et al. (1). The specific aim of our project was to develop an in vitro cell culture infectivity assay for human noroviruses (hNoV) to enhance risk assessments when they are detected in water supplies. Reverse transcription (RT) qualitative or quantitative PCR are the primary assays for waterborne NoV monitoring. However, these assays cannot distinguish between infectious vs. non-infectious virions. When hNoV is detected in water supplies, information provided by our infectivity assay will significantly improve risk assessment models and protect human health, regardless of whether we are propagating NoV. Indeed, in vitro cell culture infectivity assays for the waterborne pathogen Cryptosporidium parvum that supplement approved fluorescent microscopy assays, do not result in amplification of the environmentally resistant hard-walled oocysts (2). However, identification of life cycle stages in cell culture provides evidence of infectious oocysts in a water supply. Nonetheless, Leung et al.’s assertion regarding the suitability of our method for the in vitro propagation of high titers of NoV is valid for the medical research community. In this case, well-characterized challenge pools of virus would be useful for developing and testing diagnostics, therapeutics, and vaccines. As further validation of our published findings, we have now optimized RT quantitative PCR to assess the level of viral production in cell culture, where we are indeed finding significant increases in viral titer. The magnitude and time course of these increases is dependent on both virus strain and multiplicity of infection. We are currently preparing a manuscript that will discuss these findings in greater detail, and the implications this may have for creating viral challenge pools

  17. African Philosophy of Education as a Response to Human Rights ...

    African Journals Online (AJOL)

    Human rights violations on the African continent have emerged as a predicament for human flourishing. This article reconsiders the notion of an African philosophy of education as a response to human rights violations, in particular how the notion of Ubuntu (human interdependence and humaneness) can be used to ...

  18. Summary of human responses to ventilation

    Energy Technology Data Exchange (ETDEWEB)

    Seppanen, Olli A.; Fisk, William J.

    2004-06-01

    The effects of ventilation on indoor air quality and health is a complex issue. It is known that ventilation is necessary to remove indoor generated pollutants from indoor air or dilute their concentration to acceptable levels. But, as the limit values of all pollutants are not known, the exact determination of required ventilation rates based on pollutant concentrations and associated risks is seldom possible. The selection of ventilation rates has to be based also on epidemiological research (e.g. Seppanen et al., 1999), laboratory and field experiments (e.g. CEN 1996, Wargocki et al., 2002a) and experience (e.g. ECA 2003). Ventilation may also have harmful effects on indoor air quality and climate if not properly designed, installed, maintained and operated as summarized by Seppdnen (2003). Ventilation may bring indoors harmful substances that deteriorate the indoor environment. Ventilation also affects air and moisture flow through the building envelope and may lead to moisture problems that deteriorate the structures of the building. Ventilation changes the pressure differences over the structures of building and may cause or prevent the infiltration of pollutants from structures or adjacent spaces. Ventilation is also in many cases used to control the thermal environment or humidity in buildings. Ventilation can be implemented with various methods which may also affect health (e.g. Seppdnen and Fisk, 2002, Wargocki et al., 2002a). In non residential buildings and hot climates, ventilation is often integrated with air-conditioning which makes the operation of ventilation system more complex. As ventilation is used for many purposes its health effects are also various and complex. This paper summarizes the current knowledge on positive and negative effects of ventilation on health and other human responses. The focus of the paper is on office-type working environment and residential buildings. In the industrial premises the problems of air quality are usually

  19. A Commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It"

    Science.gov (United States)

    Everett, Jeff

    2013-01-01

    In this commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It" (McPhail 2013), the author discusses how McPhail's paper examines human rights teaching principles, the question of why corporations and business schools should respect and teach human rights, and how business…

  20. Defending Letters: A Pragmatic Response to Assaults on the Humanities

    Science.gov (United States)

    Hay, Iain

    2016-01-01

    This paper is a mainly pragmatic response to utilitarian criticisms of the humanities. It first outlines political, public and practical fronts on which the humanities are under assault, identifying critics and their conspirators. Then, as a part of its defence of the humanities it expounds some of their central strengths. These range from the…

  1. [New life: God's call--human responsibility].

    Science.gov (United States)

    Ziegler, J G

    1985-10-01

    After considering the relationship between ethical principles and their concretization in the decision of the conscience, the author names human dignity as a formal principle, and tutiorism as a material principle in the face of the beginning and end of human life. The debate which has flared up in the Federal Republic of Germany concerning abortion may be illustrated by the diverse stances adopted by bishops, physicians, legal experts and women toward the statutory provisions. A number of suggestions for help of a general nature, based on the commandment to love, and for concrete action, follow. These find their final expression in 12 synoptic theses.

  2. Human Trafficking, Globalisation and Transnational Feminist Responses

    NARCIS (Netherlands)

    T-D. Truong (Thanh-Dam)

    2014-01-01

    textabstractThis paper presents a historical overview of feminist frameworks for analysis and advocacy on human trafficking. It traces the major differences and similarities in the forms of knowledge produced since the Anti-White Slavery campaigns nearly two centuries ago. It highlights how

  3. Evolutionary Response to Human Infectious Diseases

    Science.gov (United States)

    Armelagos, George J.; Dewey, John R.

    1970-01-01

    Gives an overview of human history, relating cultural changes with resulting changes in population density and in ecological balance to patterns of infectious diseases in man. Discusses mechanisms of evolution of resistance. Suggests that in populations where infectious diseases can be controlled, attention should shift to degenerative diseases…

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Aversive Life Events Enhance Human Freezing Responses

    NARCIS (Netherlands)

    Hagenaars, M.A.; Stins, J.F.; Roelofs, K.

    2012-01-01

    In the present study, we investigated the effect of prior aversive life events on freezing-like responses. Fifty healthy females were presented neutral, pleasant, and unpleasant images from the International Affective Picture System while standing on a stabilometric platform and wearing a polar band

  6. Aversive life events enhance human freezing responses

    NARCIS (Netherlands)

    Hagenaars, M.A.; Stins, J.F.; Roelofs, K.

    2012-01-01

    In the present study, we investigated the effect of prior aversive life events on freezing-like responses. Fifty healthy females were presented neutral, pleasant, and unpleasant images from the International Affective Picture System while standing on a stabilometric platform and wearing a polar band

  7. Bioethics: New Responsibility for Human Service Administrators.

    Science.gov (United States)

    Burke, Rebecca

    The paper highlights the poignancy with which problems and issues surface as the fields of special education and bioethics (the combination of ethics and the life sciences) intersect, and touches upon professionals' responsibility for protection of the persons in their care. (Author/SBH)

  8. Dielectric response of the human tooth dentine

    Science.gov (United States)

    Leskovec, J.; Filipič, C.; Levstik, A.

    2005-07-01

    Dielectric properties of tooth dentine can be well described by the model which was developed for the dielectric response to hydrating porous cement paste. It is shown that the normalized dielectric constant and the normalized specific conductivity are proportional to the model parameters ɛ and σv, indicating the deposition of AgCl in the dentine tubules during the duration of the precipitation. The fractal dimension of the tooth dentine was determined by dielectric spectroscopy.

  9. Dielectric response of the human tooth dentine

    Energy Technology Data Exchange (ETDEWEB)

    Leskovec, J. [Dental Clinic, Faculty of Medicine, University of Ljubljana, Hrvatski trg 6, 1104 Ljubljana (Slovenia); Filipic, C. [Jozef Stefan Institute, P.O. Box 3000, 1001 Ljubljana (Slovenia); Levstik, A. [Jozef Stefan Institute, P.O. Box 3000, 1001 Ljubljana (Slovenia)]. E-mail: adrijan.levstik@ijs.si

    2005-07-15

    Dielectric properties of tooth dentine can be well described by the model which was developed for the dielectric response to hydrating porous cement paste. It is shown that the normalized dielectric constant and the normalized specific conductivity are proportional to the model parameters -bar {sub v0} and {sigma}{sub v}, indicating the deposition of AgCl in the dentine tubules during the duration of the precipitation. The fractal dimension of the tooth dentine was determined by dielectric spectroscopy.

  10. Civil society response to human trafficking in South Asia

    OpenAIRE

    Faisal Yousaf

    2006-01-01

    In South Asia civil society organisations have led the way in encouraging governments to address the problem of human trafficking. A coordinated regional response by both governments and civil society organisations is urgently required.

  11. Civil society response to human trafficking in South Asia

    Directory of Open Access Journals (Sweden)

    Faisal Yousaf

    2006-05-01

    Full Text Available In South Asia civil society organisations have led the way in encouraging governments to address the problem of human trafficking. A coordinated regional response by both governments and civil society organisations is urgently required.

  12. The effect of music on the human stress response

    National Research Council Canada - National Science Library

    Thoma, Myriam V; La Marca, Roberto; Brönnimann, Rebecca; Finkel, Linda; Ehlert, Ulrike; Nater, Urs M

    2013-01-01

    ... domains of the human stress response. Sixty healthy female volunteers (mean age = 25 years) were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test...

  13. Immune responses to chlamydial antigens in humans.

    Science.gov (United States)

    Hanna, L; Kerlan, R; Senyk, G; Stites, D P; Juster, R P; Jawetz, E

    1982-01-01

    Antibody titer, lymphocyte stimulation and leukocyte migration inhibition with chlamydial antigens were determined repeatedly over many months on human subjects. The volunteers were retrospectively placed into four groups on the basis of clinical, laboratory and epidemiologic criteria. Group A consisted of persons with proven or probable chlamydial infection, including an illness confirmed by chlamydial isolation or seroconversion, or a clinically compatible illness with positive serologic results. Group B were sexual partners or close contacts of group A individuals. Group C were laboratory workers with prolonged exposure to viable chlamydiae or their antigens. Group D included persons of comparable age as those in groups A and B, but lacking a history of symptomatic chlamydial infection or of contact with chlamydiae. Individual cases illustrated the rise of antibody and some cell mediated immunity reactions (CMI) with active chlamydial infection. By contrast, laboratory exposure resulted in elevation of CMI but not of antibody. Statistical analysis of the results in 46 volunteers tested repeatedly indicated a strong association of specific antibody with lymphocyte stimulation, but not with leukocyte migration inhibition. Regression analysis suggested that the type of exposure markedly influenced the relationship between antibody and lymphocyte stimulation. Measurement of immunotype-specific antibody titer by microimmunofluorescence (or an equally sensitive method) remains the best laboratory indicator of past chlamydial infection. Neither antibody nor CMI can, as yet, be definitely related to resistance to re-infection in humans.

  14. The radiation response of human dermal fibroblasts

    Science.gov (United States)

    Mitchell, Stephen Andrew

    A clinically reliable predictive assay based on normal-tissue radiosensitivity may lead to improved tumour control through individualised dose prescriptions. In-vitro fibroblast radiosensitivity has been shown, in several studies, to correlate with late radiation morbidity. The aim of this study was to investigate some of the cellular mechanisms underlying the normal-tissue response. In this study, seventeen primary fibroblast strains were established by enzymatic disaggregation of skin biopsies obtained from patients. These comprised seven who experienced acute tissue reactions to radiotherapy, four patients with a normal response and six non-cancer volunteers. An AT cell line was included as a positive control for radiosensitivity. In-vitro radiosensitivity was measured using a clonogenic assay at both high (HDR: 1.6 Gymin-1) and low dose rate (LDR: 0.01 Gymin-1). The radiation parameter HDR SF2 was the most sensitive in discriminating the seven sensitive patients from the remaining ten normal patients (range 0.11-0.19 sensitive patients compared with 0.17-0.34 control patients: pDNA damage. However, a strong correlation was found between clonogenic survival and both residual DNA damage (measured over 10-70 Gy, allowing 4 h repair, correlation coefficient: 0.90, DNA damage, with the sensitive cell lines generally showing a higher level of residual DNA damage. Cell-cycle delays were found in all 18 cell strains in response to 2 Gy irradiation, but were not found to discriminate between sensitive and normal patients. Associated studies found no mutations of the ATM gene in the five radiosensitive patients studied. However, a coding sequence alteration was found in the XRCC1 gene in one of the radiosensitive patients. These findings indicate that a DNA repair defect may be partly responsible for the extreme reactions to radiotherapy observed in a small percentage of patients and that with further modifications, an assay based on measurement of residual DNA damage

  15. Individual differences in human annoyance response to noise

    Science.gov (United States)

    Pearson, R. G.; Hart, F. D.; Obrien, J. F.

    1975-01-01

    Individual variations in annoyance and in susceptibility to noise were studied to establish a finer definition of the ingredients of the human annoyance response. The study involved interactions among a heterogeneous sample of human subjects, various noise stimuli, and different physical environments of exposure. Significant differences in annoyance ratings among the six noise stimuli, all equated for peak sound pressure level, were found.

  16. Human response to an individually controlled microenvironment

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor; Knudsen, G.L.

    2007-01-01

    The response of 48 subjects to an individually controlled microenvironment was studied at room air temperatures of 20 degrees C, 22 degrees C, and 26 degrees C An individually controlled system (ICS) comprising personalized ventilation, an under-desk air terminal device supplying cool air, a chair...... with convectively heated backrest, an under-desk radiant heating panel, and a floor-heating panel were used. The temperature of the air supplied from the personalized ventilation and the under-desk device was 20 degrees C The subjects were provided with control of the flow rate and direction of the personalized air...... at a room temperature of 22 degrees C without ICS. Thus, ICS will increase the number of satisfied occupants when applied in practice. The design and control of the ICS, as well as the background air distribution in a room, should be carefully considered in order to obtain the maximum number of occupants...

  17. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  18. Immune response capacity after human splenic autotransplantation - Restoration of response to individual pneumococcal vaccine subtypes

    NARCIS (Netherlands)

    Leemans, R; Manson, W; Snijder, JAM; Smit, JW; Klasen, HJ; The, TH; Timens, W

    Objective To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. Summary Background Data After splenectomy, patients

  19. Thermodynamic Modeling and Analysis of Human Stress Response

    Science.gov (United States)

    Boregowda, S. C.; Tiwari, S. N.

    1999-01-01

    A novel approach based on the second law of thermodynamics is developed to investigate the psychophysiology and quantify human stress level. Two types of stresses (thermal and mental) are examined. A Unified Stress Response Theory (USRT) is developed under the new proposed field of study called Engineering Psychophysiology. The USRT is used to investigate both thermal and mental stresses from a holistic (human body as a whole) and thermodynamic viewpoint. The original concepts and definitions are established as postulates which form the basis for thermodynamic approach to quantify human stress level. An Objective Thermal Stress Index (OTSI) is developed by applying the second law of thermodynamics to the human thermal system to quantify thermal stress or dis- comfort in the human body. The human thermal model based on finite element method is implemented. It is utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal stress responses under different environmental conditions. An innovative hybrid technique is developed to analyze human thermal behavior based on series of human-environment interaction simulations. Continuous monitoring of thermal stress is demonstrated with the help of OTSI. It is well established that the human thermal system obeys the second law of thermodynamics. Further, the OTSI is validated against the experimental data. Regarding mental stress, an Objective Mental Stress Index (OMSI) is developed by applying the Maxwell relations of thermodynamics to the combined thermal and cardiovascular system in the human body. The OMSI is utilized to demonstrate the technique of monitoring mental stress continuously and is validated with the help of series of experimental studies. Although the OMSI indicates the level of mental stress, it provides a strong thermodynamic and mathematical relationship between activities of thermal and cardiovascular systems of the human body.

  20. Improving Emergency Response and Human-Robotic Performance

    Energy Technology Data Exchange (ETDEWEB)

    David I. Gertman; David J. Bruemmer; R. Scott Hartley

    2007-08-01

    Preparedness for chemical, biological, and radiological/nuclear incidents at nuclear power plants (NPPs) includes the deployment of well trained emergency response teams. While teams are expected to do well, data from other domains suggests that the timeliness and accuracy associated with incident response can be improved through collaborative human-robotic interaction. Many incident response scenarios call for multiple, complex procedure-based activities performed by personnel wearing cumbersome personal protective equipment (PPE) and operating under high levels of stress and workload. While robotic assistance is postulated to reduce workload and exposure, limitations associated with communications and the robot’s ability to act independently have served to limit reliability and reduce our potential to exploit human –robotic interaction and efficacy of response. Recent work at the Idaho National Laboratory (INL) on expanding robot capability has the potential to improve human-system response during disaster management and recovery. Specifically, increasing the range of higher level robot behaviors such as autonomous navigation and mapping, evolving new abstractions for sensor and control data, and developing metaphors for operator control have the potential to improve state-of-the-art in incident response. This paper discusses these issues and reports on experiments underway intelligence residing on the robot to enhance emergency response.

  1. Paroxetine suppresses recombinant human P2X7 responses.

    Science.gov (United States)

    Dao-Ung, Phuong; Skarratt, Kristen K; Fuller, Stephen J; Stokes, Leanne

    2015-12-01

    P2X7 receptor (P2X7) activity may link inflammation to depressive disorders. Genetic variants of human P2X7 have been linked with major depression and bipolar disorders, and the P2X7 knockout mouse has been shown to exhibit anti-depressive-like behaviour. P2X7 is an ATP-gated ion channel and is a major regulator of the pro-inflammatory cytokine interleukin 1β (IL-1β) secretion from monocytes and microglia. We hypothesised that antidepressants may elicit their mood enhancing effects in part via modulating P2X7 activity and reducing inflammatory responses. In this study, we determined whether common psychoactive drugs could affect recombinant and native human P2X7 responses in vitro. Common antidepressants demonstrated opposing effects on human P2X7-mediated responses; paroxetine inhibited while fluoxetine and clomipramine mildly potentiated ATP-induced dye uptake in HEK-293 cells stably expressing recombinant human P2X7. Paroxetine inhibited dye uptake mediated by human P2X7 in a concentration-dependent manner with an IC(50) of 24 μM and significantly reduces ATP-induced inward currents. We confirmed that trifluoperazine hydrochloride suppressed human P2X7 responses (IC(50) of 6.4 μM). Both paroxetine and trifluoperazine did not inhibit rodent P2X7 responses, and mutation of a known residue (F 95L) did not alter the effect of either drug, suggesting neither drug binds at this site. Finally, we demonstrate that P2X7-induced IL-1β secretion from lipopolysaccharide (LPS)-primed human CD14(+) monocytes was suppressed with trifluoperazine and paroxetine.

  2. Aversive Pavlovian Responses Affect Human Instrumental Motor Performance

    Science.gov (United States)

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

    2012-01-01

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

  3. Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

    Science.gov (United States)

    Uhl, Elizabeth W; Warner, Natalie J

    Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.

  4. Changes in Somatosensory Responsiveness in Behaving Monkeys and Human Sub

    Science.gov (United States)

    1991-08-30

    MONITORING ORGANIZATION REPORT NUOf1BE(S) Department of Anatomy and Neurobiology University of Tennessee, Memphis Sa. NAME OF PERFORMING ORGANIZATION 6b...and monkeys make ballistic movements more quickly (50-100 msec) in response to vibratory as compared to visual signals. Human subjects also make...quickly (50-100 msec) in response to vibratory as compared to visual signals. Subjects also make movements more quickly to a visual target if, in addition

  5. The photocurrent response of human cones is fast and monophasic

    Directory of Open Access Journals (Sweden)

    Lamb TD

    2006-04-01

    Full Text Available Abstract Background The precise form of the light response of human cone photoreceptors in vivo has not been established with certainty. To investigate the response shape we compare the predictions of a recent model of transduction in primate cone photoreceptors with measurements extracted from human cones using the paired-flash electroretinogram method. As a check, we also compare the predictions with previous single-cell measurements of ground squirrel cone responses. Results The predictions of the model provide a good description of the measurements, using values of parameters within the range previously determined for primate retina. The dim-flash response peaks in about 20 ms, and flash responses at all intensities are essentially monophasic. Three time constants in the model are extremely short: the two time constants for inactivation (of visual pigment and of transducin/phosphodiesterase are around 3 and 10 ms, and the time constant for calcium equilibration lies in the same range. Conclusion The close correspondence between experiment and theory, using parameters previously derived for recordings from macaque retina, supports the notion that the electroretinogram approach and the modelling approach both provide an accurate estimate of the cone photoresponse in the living human eye. For reasons that remain unclear, the responses of isolated photoreceptors from the macaque retina, recorded previously using the suction pipette method, are considerably slower than found here, and display biphasic kinetics.

  6. Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

    Directory of Open Access Journals (Sweden)

    Nigel G. Kooreman

    2017-08-01

    Full Text Available There is growing interest in using embryonic stem cell (ESC and induced pluripotent stem cell (iPSC derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

  7. Emotional contagion: dogs and humans show a similar physiological response to human infant crying.

    Science.gov (United States)

    Yong, Min Hooi; Ruffman, Ted

    2014-10-01

    Humans respond to an infant crying with an increase in cortisol level and heightened alertness, a response interpreted as emotional contagion, a primitive form of empathy. Previous results are mixed when examining whether dogs might respond similarly to human distress. We examined whether domestic dogs, which have a long history of affiliation with humans, show signs of emotional contagion, testing canine (n=75) and human (n=74) responses to one of three auditory stimuli: a human infant crying, a human infant babbling, and computer-generated "white noise", with the latter two stimuli acting as controls. Cortisol levels in both humans and dogs increased significantly from baseline only after listening to crying. In addition, dogs showed a unique behavioral response to crying, combining submissiveness with alertness. These findings suggest that dogs experience emotional contagion in response to human infant crying and provide the first clear evidence of a primitive form of cross-species empathy. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Seasonal changes in human immune responses to malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G

    1993-01-01

    Cellular as well as humorol immune responses to malaria antigens fluctuate in time in individuals living in molono-endemic areas, particularly where malaria transmission is seasonal. The most pronounced changes are seen in association with clinical attacks, but osymptomatic infection can also lead...... to apparent immune depression. However, recent data have shown that seasonal variation in cellular immune responses may occur even in the absence of detectable porositaemia. Here, Lars Hviid and Thor G. Theonder review the seasonal variation in human immune responses to malaria, and discuss its possible...... causes and implications....

  9. Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response.

    Directory of Open Access Journals (Sweden)

    Anja Kathrin Wege

    Full Text Available BACKGROUND: Leishmania (L. species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis. CONCLUSIONS/SIGNIFICANCE: This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral leishmaniasis allowing the investigation of human immune response, side effects of the drug

  10. Using Thermodynamic Degradation Approach to Quantify Human Stress Response

    Directory of Open Access Journals (Sweden)

    Satish Boregowda

    2017-01-01

    Full Text Available The present study provides a thermodynamic degradation approach to model human stress response. Finger skin temperature was used as an indicator of stress response to a stressor (or stressful event followed by a recovery. The entropy change (ΔS is calculated using heat transfer (δQ from the peripheral skin and finger skin temperature (Tf. It was hypothesized that the human stress response, as evidenced by finger skin temperature change, is a quasi-static process. The entropy approach is demonstrated using data from a medical school experimental study. The finger skin temperature was measured under three conditions (relaxation, stressor task, and recovery during the physiological test profile. The entropy change (ΔS is postulated as entropy damage (ΔSD, which is a metric for measuring the aging or system degradation. The aging-ratio, Aaging-ratio, that is, the ratio of entropy change due to stressor to that of recovery, is presented for both male and female subjects. The statistical t-tests demonstrate statistical significance in human stress response to stressor and recovery states within and between male and female subjects. This novel approach could be valuable to medical researchers, particularly in the field of occupational health to evaluate human exposure to stressful environments.

  11. Response of neotropical bat assemblages to human land use.

    Science.gov (United States)

    García-Morales, Rodrigo; Badano, Ernesto I; Moreno, Claudia E

    2013-10-01

    Neotropical bats are sensitive to human-induced habitat changes, and some authors believe bats can be used as bioindicators. In the literature, however, the results are disparate. Some results show bat diversity deceases as disturbance increases, whereas others indicate no effect. Determining the general response patterns of bats when they encounter different degrees of human-induced disturbance across the Neotropics would help to determine their usefulness as bioindicators. In a series of meta-analyses, we compared the occurrence frequency of bat species between well-preserved forests and human-use areas. We obtained data through an extensive review of published peer-reviewed articles, theses, and reports. The overall effect size indicated that human-use areas harbored more bat species than well-preserved forests. Different response patterns emerged when meta-analyses were conducted separately by family, feeding habit, vegetation stratum, and conservation status. Our results suggest that bat assemblages display strong responses to forest loss and land-use change and that the direction and magnitude of these responses depends on the bat group under study and the type of disturbance. Our results are consistent with the idea that bats are useful for assessing the effects of habitat changes in the Neotropics. However, with our meta-analyses we could not detect fine differences in bat feeding habits, especially within Phyllostomidae, or elucidate the effect of landscape configuration. © 2013 Society for Conservation Biology.

  12. Human volunteer head-Tl response for oblique impact conditions

    NARCIS (Netherlands)

    Philippens, M.M.G.M.; Cappon, H.J.; Ratingen, M.R. van

    2004-01-01

    The development of modern smart restraint systems requires access to human surrogates with a biofidelic performance, which includes details on timing and local deformations. Therefore volunteer head neck responses for oblique impacts from the Naval BioDynamics Laboratory are re-analysed using a

  13. Response of midpiece vesicles on human sperm to osmotic stress

    DEFF Research Database (Denmark)

    Abraham-Peskir, Joanna V; Chantler, Eric; Uggerhøj, Erik

    2002-01-01

    BACKGROUND: We investigated the osmotic response of midpiece vesicles (MPV) on human sperm. METHODS: Light microscopy, transmission X-ray microscopy and computer-aided semen analysis was used to investigate sperm in normozoospermic semen from healthy donors, separated from semen and suspended...

  14. Sex hormones and the immune response in humans

    NARCIS (Netherlands)

    Bouman, Annechien; Heineman, Maas Jan; Faas, Marijke M.

    2005-01-01

    In addition to their effects on sexual differentiation and reproduction, sex hormones appear to influence the immune system. This results in a sexual dimorphism in the immune response in humans: for instance, females produce more vigorous cellular and more vigorous humoral immune reactions, are more

  15. Stress-induced responses of human skin fibroblasts in vitro reflect human longevity

    NARCIS (Netherlands)

    Dekker, Pim; Maier, Andrea B.; van Heemst, Diana; de Koning-Treurniet, Corine; Blom, Joke; Dirks, Roeland W.; Tanke, Hans J.; Westendorp, Rudi G.J.

    2009-01-01

    Unlike various model organisms, cellular responses to stress have not been related to human longevity. We investigated cellular responses to stress in skin fibroblasts that were isolated from young and very old subjects, and from offspring of nonagenarian siblings and their partners, representatives

  16. Attribution, Responsibility and Jurisdiction in International Human Rights Law

    Directory of Open Access Journals (Sweden)

    Lucius Caflisch

    2017-03-01

    Full Text Available This paper deals with the attribution of responsibility to States Parties for violations of selected multilateral human rights treaties outside their territory, and the jurisdiction of the treaty organs over such violations. Jurisdiction over human rights violations may result from territorial sovereignty, but also from quasi-territorial domination (occupation and similar situations, jurisdiction over marine spaces or from the exercise of personal jurisdiction such as activities by consular, diplomatic, or intelligence agents in foreign countries, acts by or on vessels on the high seas, or on air or space craft. For each of the treaty systems examined (African Charter of Human and Peoples’ Rights, American Convention on Human Rights, United Nations Covenant on Civil and Political Rights, European Convention on Human Rights, this contribution describes the system’s general features, its provisions on jurisdiction, and most importantly, the practices it generates. This allows for a number of conclusions: that all the mechanisms examined contain some compulsory elements, that all of them except the African system contain pertinent rules, and that all of these  mechanisms apply the classical rules of international law on the exercise of quasi-territorial and personal jurisdiction. States are responsible for the breaches of human rights standards committed by their agents and organs in the exercise of such jurisdiction, and treaty organs are entitled to deal with such breaches.

  17. Collective response of human populations to large-scale emergencies

    CERN Document Server

    Bagrow, James P; Barabási, Albert-László; 10.1371/journal.pone.0017680

    2011-01-01

    Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response.

  18. Collective Response of Human Populations to Large-Scale Emergencies

    Science.gov (United States)

    Barabási, Albert-László

    2011-01-01

    Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response. PMID:21479206

  19. Human Trafficking in Nepal: Post-Earthquake Risk and Response.

    Science.gov (United States)

    Gyawali, Bishal; Keeling, June; Kallestrup, Per

    2017-04-01

    As Nepal mourns the 1-year commemoration of the April 2015 earthquake and its aftershocks that killed more than 8500 people and left thousands injured and displaced, other more hidden repercussions of the resultant chaotic environment need attention: the increased risk of human trafficking. Considering that natural disasters provide a milieu for this illicit trade, there is a need for a robust response from stakeholders such as donors, civil society organizations, and government organizations against human trafficking following disasters such as the Nepal earthquake. Responsibility to prevent and fight trafficking should be explicitly included in the mandate of relief and rehabilitation mechanisms set up at the national level to coordinate the disaster relief response, serving to support populations in both rural and urban areas. (Disaster Med Public Health Preparedness. 2017;11:153-154).

  20. Collective response of human populations to large-scale emergencies.

    Directory of Open Access Journals (Sweden)

    James P Bagrow

    Full Text Available Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response.

  1. Variability in responses observed in human white adipose tissue models.

    Science.gov (United States)

    Abbott, Rosalyn D; Borowsky, Francis E; Alonzo, Carlo A; Zieba, Adam; Georgakoudi, Irene; Kaplan, David L

    2017-09-06

    Obesity is a risk factor for a myriad of diseases including diabetes, cardiovascular dysfunction, cirrhosis, and cancer, and there is a need for new systems to study how excess adipose tissue relates to the onset of disease processes. This study provides proof-of-concept patient-specific tissue models of human white adipose tissue to accommodate the variability in human samples. Our 3D tissue engineering approach established lipolytic responses and changes in insulin-stimulated glucose uptake from small volumes of human lipoaspirate, making this methodology useful for patient specific sample source assessments of treatment strategies, drug responses, disease mechanisms, and other responses that vary between patients. Mature unilocular cells were maintained ex vivo in silk porous scaffolds for up to a month of culture and imaged non-invasively with coherent anti-Stokes Raman scattering. Interestingly, differences in responsiveness between tissues were observed in terms of magnitude of lipolysis, ability to suppress lipolysis, differences in glucose uptake, and lipid droplet size. Body mass index was not a factor in determining tissue responsiveness; rather, it is speculated that other unknown variables in the backgrounds of different patients (ethnicity, athleticism, disease history, lifestyle choices, etc.) likely had a more significant effect on the observed differences. This study reinforces the need to account for the variability in backgrounds and genetics within the human population to determine adipose tissue responsiveness. In the future, this tissue system could be used to inform individualized care strategies-enhancing therapeutic precision, improving patient outcomes, and reducing clinical costs. Copyright © 2017 John Wiley & Sons, Ltd.

  2. The immune response of the human brain to abdominal surgery

    DEFF Research Database (Denmark)

    Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin

    2017-01-01

    OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans....... This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general...... to change in [(11) C]PBR28 binding (p = 0.027). INTERPRETATION: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may...

  3. Modulation of Human Immune Response by Fungal Biocontrol Agents

    Science.gov (United States)

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

    2017-01-01

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

  4. Climate change in the oceans: Human impacts and responses.

    Science.gov (United States)

    Allison, Edward H; Bassett, Hannah R

    2015-11-13

    Although it has far-reaching consequences for humanity, attention to climate change impacts on the ocean lags behind concern for impacts on the atmosphere and land. Understanding these impacts, as well as society's diverse perspectives and multiscale responses to the changing oceans, requires a correspondingly diverse body of scholarship in the physical, biological, and social sciences and humanities. This can ensure that a plurality of values and viewpoints is reflected in the research that informs climate policy and may enable the concerns of maritime societies and economic sectors to be heard in key adaptation and mitigation discussions. Copyright © 2015, American Association for the Advancement of Science.

  5. Healthy human T-Cell Responses to Aspergillus fumigatus antigens.

    Science.gov (United States)

    Chaudhary, Neelkamal; Staab, Janet F; Marr, Kieren A

    2010-02-17

    Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H)1-T(H)17) and destructive allergic (T(H)2) immunity. How Aspergillus allergens (Asp f proteins) participate in the development of allergic sensitization is unknown. To determine whether Asp f proteins are strictly associated with T(H)2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17) to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H)1-responses to Asp f3 (a putative peroxismal membrane protein), Asp f9/16 (cell wall glucanase), Asp f11 (cyclophilin type peptidyl-prolyl isomerase) and Asp f22 (enolase). Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals. Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.

  6. Healthy human T-Cell Responses to Aspergillus fumigatus antigens.

    Directory of Open Access Journals (Sweden)

    Neelkamal Chaudhary

    2010-02-01

    Full Text Available Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H1-T(H17 and destructive allergic (T(H2 immunity. How Aspergillus allergens (Asp f proteins participate in the development of allergic sensitization is unknown.To determine whether Asp f proteins are strictly associated with T(H2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17 to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H1-responses to Asp f3 (a putative peroxismal membrane protein, Asp f9/16 (cell wall glucanase, Asp f11 (cyclophilin type peptidyl-prolyl isomerase and Asp f22 (enolase. Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals.Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.

  7. Auditory Brainstem Responses to Continuous Natural Speech in Human Listeners.

    Science.gov (United States)

    Maddox, Ross K; Lee, Adrian K C

    2018-01-01

    Speech is an ecologically essential signal, whose processing crucially involves the subcortical nuclei of the auditory brainstem, but there are few experimental options for studying these early responses in human listeners under natural conditions. While encoding of continuous natural speech has been successfully probed in the cortex with neurophysiological tools such as electroencephalography (EEG) and magnetoencephalography, the rapidity of subcortical response components combined with unfavorable signal-to-noise ratios signal-to-noise ratio has prevented application of those methods to the brainstem. Instead, experiments have used thousands of repetitions of simple stimuli such as clicks, tone-bursts, or brief spoken syllables, with deviations from those paradigms leading to ambiguity in the neural origins of measured responses. In this study we developed and tested a new way to measure the auditory brainstem response (ABR) to ongoing, naturally uttered speech, using EEG to record from human listeners. We found a high degree of morphological similarity between the speech-derived ABRs and the standard click-evoked ABR, in particular, a preserved Wave V, the most prominent voltage peak in the standard click-evoked ABR. Because this method yields distinct peaks that recapitulate the canonical ABR, at latencies too short to originate from the cortex, the responses measured can be unambiguously determined to be subcortical in origin. The use of naturally uttered speech to measure the ABR allows the design of engaging behavioral tasks, facilitating new investigations of the potential effects of cognitive processes like language and attention on brainstem processing.

  8. Observation of the human body thermoregulation and extraction of its vein signature using NIR and MWIR imaging

    Science.gov (United States)

    Bouzida, Nabila; Bendada, Abdelhakim; Maldague, Xavier P.

    2009-05-01

    The article aims first to present a new study on the thermal regulatory response of the human skin surface while exposed to a cold environment. Our work has shown that when a cold stress is applied to the left hand, thermal infrared imaging (MWIR spectral band: 3-5 μm) allows a clear observation of a temperature rise on the right hand. Moreover, a frequency analysis was also carried out upon selected vein pixels of the images monitored during the same cold stress experiment. The objective was to identify the specific frequencies that could be linked to some physiological mechanisms of the human body. This kind of study could be very useful for the characterization of possible thermo-physiological pathologies. Besides thermoregulation, we also present in this article some results on the extraction of the hand vein pattern. Firstly, we show some vein extraction results obtained after image processing of the thermal images recorded in the thermal band (MWIR), then we compare this vein pattern to the signature obtained with a camera operating in the NIR spectral band (0.85-1.7 μm). This method could be used as a complementary means for finger print signatures in biometrics.

  9. Response inhibition during perceptual decision making in humans and macaques

    Science.gov (United States)

    Middlebrooks, Paul G.

    2014-01-01

    Response inhibition in stop signal tasks has been explained as the outcome of a race between GO and STOP processes (e.g., Logan, 1981). Response choice in two-alternative perceptual categorization tasks has been explained as the outcome of an accumulation of evidence for the alternative responses. To begin unifying these two powerful investigation frameworks, we obtained data from humans and macaque monkeys performing a stop signal task with responses guided by perceptual categorization and variable degrees of difficulty, ranging from low to high accuracy. Comparable results across species reinforced the validity of this animal model. Response times and errors increased with categorization difficulty. The probability of failing to inhibit responses on stop signal trials increased with stop signal delay, and the response times for failed stop signal trials were shorter than those for trials with no stop signal. Thus, the Logan race model could be applied to estimate the duration of the stopping process. We found that the duration of the STOP process did not vary across a wide range of discrimination accuracies. This is consistent with the functional, and possibly mechanistic, independence of choice and inhibition mechanisms. PMID:24306985

  10. Are Children with Autism More Responsive to Animated Characters? A Study of Interactions with Humans and Human-Controlled Avatars

    Science.gov (United States)

    Carter, Elizabeth J.; Williams, Diane L.; Hodgins, Jessica K.; Lehman, Jill F.

    2014-01-01

    Few direct comparisons have been made between the responsiveness of children with autism to computer-generated or animated characters and their responsiveness to humans. Twelve 4-to 8-year-old children with autism interacted with a human therapist; a human-controlled, interactive avatar in a theme park; a human actor speaking like the avatar; and…

  11. Frequency response of human vestibular reflexes characterized by stochastic stimuli.

    Science.gov (United States)

    Dakin, Christopher J; Son, Gregory M Lee; Inglis, J Timothy; Blouin, Jean-Sébastien

    2007-09-15

    Stochastic vestibular stimulation (SVS) can be used to study the postural responses to unpredictable vestibular perturbations. The present study seeks to determine if stochastic vestibular stimulation elicits lower limb muscular responses and to estimate the frequency characteristics of these vestibulo-motor responses in humans. Fourteen healthy subjects were exposed to unpredictable galvanic currents applied on their mastoid processes while quietly standing (+/-3 mA, 0-50 Hz). The current amplitude and stimulation configuration as well as the subject's head position relative to their feet were manipulated in order to determine that: (1) the muscle responses evoked by stochastic currents are dependent on the amplitude of the current, (2) the muscle responses evoked by stochastic currents are specific to the percutaneous stimulation of vestibular afferents and (3) the lower limb muscle responses exhibit polarity changes with different head positions as previously described for square-wave galvanic vestibular stimulation (GVS) pulses. Our results revealed significant coherence (between 0 and 20 Hz) and cumulant density functions (peak responses at 65 and 103 ms) between SVS and the lower limbs' postural muscle activity. The polarity of the cumulant density functions corresponded to that of the reflexes elicited by square-wave GVS pulses. The SVS-muscle activity coherence and time cumulant functions were modulated by current amplitude, electrode position and head orientation with respect to the subject's feet. These findings strongly support the vestibular origin of the lower limb muscles evoked by SVS. In addition, specific frequency bandwidths in the stochastic vestibular signal contributed to the early (12-20 Hz) and late components (2-10 Hz) of the SVS-evoked muscular responses. These frequency-dependent SVS-evoked muscle responses support the view that the biphasic muscle response is conveyed by two distinct physiological processes.

  12. Modulation of human immune responses by bovine interleukin-10.

    Directory of Open Access Journals (Sweden)

    Gerco den Hartog

    Full Text Available Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood monocytes were isolated from healthy donors, and used directly or allowed to differentiate to dendritic cells under the influence of IL-4 and GM-CSF. Recombinant bovine IL-10 inhibited TLR induced activation of monocytes, and dose-dependently inhibited LPS-induced activation of monocyte-derived DCs comparable to human IL-10. By using blocking antibodies to either bovine IL-10 or the human IL-10 receptor it was demonstrated that inhibition of monocyte activation by bovine IL-10 was dependent on binding of bovine IL-10 to the human IL-10R. These data demonstrate that bovine IL-10 potently inhibits the activation of human myeloid cells in response to TLR activation. Bovine IL-10 present in dairy products may thus potentially contribute to the prevention of necrotizing enterocolitis and allergy, enhance mucosal tolerance induction and decrease intestinal inflammation and may therefore be applicable in infant foods and in immunomodulatory diets.

  13. Serotonin modulates striatal responses to fairness and retaliation in humans

    Science.gov (United States)

    Crockett, MJ; Apergis-Schoute, AM; Herrmann, B; Lieberman, MD; Müller, U; Robbins, TW; Clark, L

    2013-01-01

    Humans are willing to incur personal costs to punish others who violate social norms. Such ‘costly punishment’ is an important force for sustaining human cooperation, but the causal neurobiological determinants of punishment decisions remain unclear. Using a combination of behavioral, pharmacological and neuroimaging techniques, we show that manipulating the serotonin system in humans alters costly punishment decisions by modulating responses to fairness and retaliation in the striatum. Following dietary depletion of the serotonin precursor tryptophan, participants were more likely to punish those who treated them unfairly, and were slower to accept fair exchanges. Neuroimaging data revealed activations in the ventral and dorsal striatum that were associated with fairness and punishment, respectively. Depletion simultaneously reduced ventral striatal responses to fairness and increased dorsal striatal responses during punishment, an effect that predicted its influence on punishment behavior. Finally, we provide behavioral evidence that serotonin modulates specific retaliation, rather than general norm enforcement: depleted participants were more likely to punish unfair behavior directed toward themselves, but not unfair behavior directed toward others. Our findings demonstrate that serotonin modulates social value processing in the striatum, producing context-dependent effects on social behavior. PMID:23426678

  14. FCJ-195 Privacy, Responsibility, and Human Rights Activism

    Directory of Open Access Journals (Sweden)

    Becky Kazansky

    2015-06-01

    Full Text Available In this article, we argue that many difficulties associated with the protection of digital privacy are rooted in the framing of privacy as a predominantly individual responsibility. We examine how models of privacy protection, such as Notice and Choice, contribute to the ‘responsibilisation’ of human rights activists who rely on the use of technologies for their work. We also consider how a group of human rights activists countered technology-mediated threats that this ‘responsibilisation’ causes by developing a collective approach to address their digital privacy and security needs. We conclude this article by discussing how technological tools used to maintain or counter the loss of privacy can be improved in order to support the privacy and digital security of human rights activists.

  15. Alternative Responses to the Human Resource Challenge for CBR

    Directory of Open Access Journals (Sweden)

    Huib Cornielje

    2013-02-01

    Full Text Available This commentary outlines some ways of understanding CBR and offers corresponding suggestions for responding to the contemporary human resource challenge it is faced with. It is argued that CBR exists within an increasingly complex reality, characterised by new challenges, new approaches to development and numerous international principles and guidelines.  In response, the authors advocate the use of multiple research methods, participatory action and contextualised ways of addressing human resource issues.  They suggest that new understandings are required, for future CBR workers to be enablers of people with disabilities, agents of change in communities and societies, and champions of human rights.  The complex reality of CBR suggests the need for a CBR cadre which is capable of creative and reflective reasoning.  This might be achieved through the participatory development of contextualised training curricula, practical hands-on learning, the use of mentoring, and an emphasis on reflection and adaptability.

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

    Science.gov (United States)

    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.

  17. Catecholamine responses to changes in posture during human pregnancy.

    Science.gov (United States)

    Whittaker, P G; Gerrard, J; Lind, T

    1985-06-01

    Human pregnancy may induce changes in the sensitivity of the cardiovascular system to endogenous catecholamines. This was investigated in multigravid women with little likelihood of unsuspected vascular disease. The responses of blood pressure, pulse rate, plasma noradrenaline and adrenaline to a change in posture from semi-recumbency to standing were assessed in six normotensive women at 36 weeks gestation and in six non-pregnant control subjects. Standing for 10 min caused a surge in blood pressure, pulse rate and plasma noradrenaline in non-pregnant women. The pregnant women, whose basal levels of noradrenaline were higher than those in non-pregnant women, showed a slower noradrenergic response to postural change, and this response had less effect upon the cardiovascular indices. Blood pressure dropped immediately on standing and pulse rate remained unaffected throughout. It is suggested that some women may maintain a non-pregnant level of pressor sensitivity during pregnancy and thereby become hypertensive.

  18. Cell mediated immune response in human antirabies revaccination

    Directory of Open Access Journals (Sweden)

    Débora Regina Veiga

    1987-04-01

    Full Text Available The occurrence of secondary cell mediated immune response (CMI in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

  19. Neurobiological determinism: human freedom of choice and criminal responsibility.

    Science.gov (United States)

    Urbaniok, Frank; Laubacher, Arja; Hardegger, Judith; Rossegger, Astrid; Endrass, Jérôme; Moskvitin, Konstantin

    2012-04-01

    Several authors have argued that criminal behavior is generally caused by neurobiological deficits. This assumption not only questions the concept of free will and a person's responsibility for his or her own actions but also the principle of guilt in criminal law. When critically examining the current state of research, it becomes apparent that the results are not sufficient to support the existence of a universally valid neurobiological causality of criminal behavior. Moreover, the assumption of total neurobiological determination of human behavior and the impossibility of individual responsibility are characterized by both faulty empiricism and methodical misconceptions. The principle of relative determinism and the analysis of the offender's behavior at the time of the offense thus remain the central and cogent approach to the assessment of criminal responsibility.

  20. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

  1. Neandertal versus Modern Human Dietary Responses to Climatic Fluctuations

    Science.gov (United States)

    El Zaatari, Sireen; Grine, Frederick E.; Ungar, Peter S.; Hublin, Jean-Jacques

    2016-01-01

    The Neandertal lineage developed successfully throughout western Eurasia and effectively survived the harsh and severely changing environments of the alternating glacial/interglacial cycles from the middle of the Pleistocene until Marine Isotope Stage 3. Yet, towards the end of this stage, at the time of deteriorating climatic conditions that eventually led to the Last Glacial Maximum, and soon after modern humans entered western Eurasia, the Neandertals disappeared. Western Eurasia was by then exclusively occupied by modern humans. We use occlusal molar microwear texture analysis to examine aspects of diet in western Eurasian Paleolithic hominins in relation to fluctuations in food supplies that resulted from the oscillating climatic conditions of the Pleistocene. There is demonstrable evidence for differences in behavior that distinguish Upper Paleolithic humans from members of the Neandertal lineage. Specifically, whereas the Neandertals altered their diets in response to changing paleoecological conditions, the diets of Upper Paleolithic humans seem to have been less affected by slight changes in vegetation/climatic conditions but were linked to changes in their technological complexes. The results of this study also indicate differences in resource exploitation strategies between these two hominin groups. We argue that these differences in subsistence strategies, if they had already been established at the time of the first contact between these two hominin taxa, may have given modern humans an advantage over the Neandertals, and may have contributed to the persistence of our species despite habitat-related changes in food availabilities associated with climate fluctuations. PMID:27119336

  2. Neandertal versus Modern Human Dietary Responses to Climatic Fluctuations.

    Directory of Open Access Journals (Sweden)

    Sireen El Zaatari

    Full Text Available The Neandertal lineage developed successfully throughout western Eurasia and effectively survived the harsh and severely changing environments of the alternating glacial/interglacial cycles from the middle of the Pleistocene until Marine Isotope Stage 3. Yet, towards the end of this stage, at the time of deteriorating climatic conditions that eventually led to the Last Glacial Maximum, and soon after modern humans entered western Eurasia, the Neandertals disappeared. Western Eurasia was by then exclusively occupied by modern humans. We use occlusal molar microwear texture analysis to examine aspects of diet in western Eurasian Paleolithic hominins in relation to fluctuations in food supplies that resulted from the oscillating climatic conditions of the Pleistocene. There is demonstrable evidence for differences in behavior that distinguish Upper Paleolithic humans from members of the Neandertal lineage. Specifically, whereas the Neandertals altered their diets in response to changing paleoecological conditions, the diets of Upper Paleolithic humans seem to have been less affected by slight changes in vegetation/climatic conditions but were linked to changes in their technological complexes. The results of this study also indicate differences in resource exploitation strategies between these two hominin groups. We argue that these differences in subsistence strategies, if they had already been established at the time of the first contact between these two hominin taxa, may have given modern humans an advantage over the Neandertals, and may have contributed to the persistence of our species despite habitat-related changes in food availabilities associated with climate fluctuations.

  3. Neandertal versus Modern Human Dietary Responses to Climatic Fluctuations.

    Science.gov (United States)

    El Zaatari, Sireen; Grine, Frederick E; Ungar, Peter S; Hublin, Jean-Jacques

    2016-01-01

    The Neandertal lineage developed successfully throughout western Eurasia and effectively survived the harsh and severely changing environments of the alternating glacial/interglacial cycles from the middle of the Pleistocene until Marine Isotope Stage 3. Yet, towards the end of this stage, at the time of deteriorating climatic conditions that eventually led to the Last Glacial Maximum, and soon after modern humans entered western Eurasia, the Neandertals disappeared. Western Eurasia was by then exclusively occupied by modern humans. We use occlusal molar microwear texture analysis to examine aspects of diet in western Eurasian Paleolithic hominins in relation to fluctuations in food supplies that resulted from the oscillating climatic conditions of the Pleistocene. There is demonstrable evidence for differences in behavior that distinguish Upper Paleolithic humans from members of the Neandertal lineage. Specifically, whereas the Neandertals altered their diets in response to changing paleoecological conditions, the diets of Upper Paleolithic humans seem to have been less affected by slight changes in vegetation/climatic conditions but were linked to changes in their technological complexes. The results of this study also indicate differences in resource exploitation strategies between these two hominin groups. We argue that these differences in subsistence strategies, if they had already been established at the time of the first contact between these two hominin taxa, may have given modern humans an advantage over the Neandertals, and may have contributed to the persistence of our species despite habitat-related changes in food availabilities associated with climate fluctuations.

  4. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (TFH) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of TFH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on TFH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate TFH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing TFH cell maturation. In cocultures they differentiated B cells into CD138(+) plasma and IgD(-)CD27(+) memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented TFH cell development. Added to TFH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3(+)CXCR5(+)PD-1(+) follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on TFH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control TFH cell maturation, expand follicular regulatory T cells, and inhibit the TFH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the TFH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. [Melatonin reduces cortisol response to ACTH in humans].

    Science.gov (United States)

    Campino, Carmen; Valenzuela, Francisco; Arteaga, Eugenio; Torres-Farfán, Claudia; Trucco, Cristián; Velasco, Alfredo; Guzmán, Sergio; Serón-Ferré, María

    2008-11-01

    Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland. To assess if the human adrenal gland expresses melatonin receptors and if melatonin affects cortisol response to ACTH in dexamethasone suppressed volunteers. Adrenal glands were obtained from 4 patients undergoing unilateral nephrectomy-adrenalectomy for renal cancer. Expression of mRNA MT1 and MT2 melatonin receptors was measured by Reverse TranscriPtase Polymerase Chain Reaction (RT-PCR). The effect of melatonin on the response to intravenous (i.v.) ACTH was tested (randomized cross-over, double-blind, placebo-controlled trial) in eight young healthy males pretreated with dexamethasone (1 mg) at 23:00 h. On the next day, at 08:00 h, an i.v. line was inserted, at 08:30 h, and after a blood sample, subjects ingested 6 mg melatonin or placebo. At 09:00 h, 1-24 ACTH (Cortrosyn, 1 microg/1.73 m2 body surface area) was injected, drawing samples at 0, 15, 30, 45 and 60 minutes after. Melatonin, cortisol, cortisone, progesterone, aldosterone, DHEA-S, testosterone and prolactin were measured by immunoassay. The four adrenal glands expressed only MT1 receptor mRNA. Melatonin ingestion reduced the cortisol response to ACTH from 14.6 +/- 1.45 microg/dl at 60 min in the placebo group to 10.8 +/- 1.2 microg/dl in the melatonin group (p melatonin receptor in the human adrenal, and the melatonin reduction of ACTH-stimulated cortisol production suggest a direct melatonin action on the adrenal gland.

  6. Wheal and flare responses to muscle relaxants in humans.

    Science.gov (United States)

    Levy, J H; Adelson, D; Walker, B

    1991-11-01

    Chemically and pharmacologically unrelated molecules release histamine in humans to produce both cutaneous and systemic responses. It has been suggested that molecular changes in the new benzylisoquinoline-derived muscle relaxant, atracurium, make it less likely to cause histamine release. We therefore injected volunteers intradermally with equimolar concentrations of various muscle relaxants, morphine, papaverine (a benzylisoquinoline), and histamine, to evaluate the relative ability of these drugs to cause wheal and flare responses, and mast-cell degranulation. There were no significant differences in wheal and flare responses among the three benzylisoquinoline-derived muscle relaxants, D-tubocurarine, metocurine, and atracurium. The cutaneous effects of morphine were significantly greater than those of the benzylisoquinoline muscle relaxants, suggesting both direct vascular changes and histamine release. Papaverine injection was followed by a significant wheal but no flare. Skin biopsies from vecuronium- and papaverine-induced wheals revealed normal intact mast-cell granules, suggesting a direct cutaneous vascular response rather than histamine release. Skin biopsies after morphine and atracurium injections revealed mast-cell degranulation. All evaluated benzylisoquinoline muscle relaxants are equipotent histamine releasers at equimolar concentrations. A hydrogenated, benzylisoquinoline-nitrogen-containing ring, present in atracurium but not in papaverine, appears to be the molecular conformation responsible for mast-cell degranulation by atracurium.

  7. Crossing Thresholds - Human Responses to Tsunami Forcing in the Pacific

    Science.gov (United States)

    Goff, J. R.; Chague-Goff, C.

    2014-12-01

    The 11 March 2011 Tohoku-oki tsunami caused widespread devastation to coastal communities in Japan. This event however was merely the latest in a long line of similar occurrences throughout the Pacific over time. All the recent large tsunamis have had their predecessors, and a growing database of palaeotsunamis in the Pacific suggests that several past events have been either similar in magnitude or greater than their historical counterparts. Not only are we gathering data concerning Pacific palaeotsunamis but we are also identifying contemporaneous punctuated histories of changing human settlement patterns across the Pacific. In particular, the almost two millennia 'long pause' in eastward Polynesian migration and the abandonment of long distance sea-voyaging in the 15th century. It is suggested that large palaeotsunamis and their generating mechanisms forced major societal responses. Given the unquestioned impacts of recent tsunamis on human societies, it is reasonable to suggest that past societal responses can be used as proxies for contemporaneous environmental forcing in those parts of the world where independent evidence of the effects of these events is still being gathered. In the Pacific there are a range of responses that extend well beyond the abandonment of long distance sea-voyaging such as the outbreak of region-wide conflict and the associated abandonment of settlements in exposed (coastal) locations. The contemporaneity of these effects across a vast region requires a driver that is external to particular island groups. Given that this must have impacted coastal resources severely and enduringly, the only possibility is that this driver was of oceanic origin. This hypothesis is compelling when considered alongside the growing database of more conventional lines of evidence. The question therefore is how well are similar threshold responses recognised throughout the World? Are there similar region-wide responses that have been pigeonholed under the

  8. Skeletal muscle responses to lower limb suspension in humans

    Science.gov (United States)

    Hather, Bruce M.; Adams, Gregory R.; Tesch, Per A.; Dudley, Gary A.

    1992-01-01

    The morphological responses of human skeletal muscle to unweighting were assessed by analyzing multiple transaxial magnetic resonance (MR) images of both lower limbs and skeletal muscle biopsies of the unweighted lower limb before and after six weeks of unilaterial (left) lower limb suspension (ULLS). Results indicated that, as a results of 6 weeks of unweighting (by the subjects walking on crutches using only one limb), the cross sectional area (CSA) of the thigh muscle of the unweighted left limb decreased 12 percent, while the CSA of the right thigh muscle did not change. The decrease was due to a twofold greater response of the knee extensors than the knee flexors. The pre- and post-ULLS biopsies of the left vastus lateralis showed a 14 percent decrease in average fiber CSA due to unweighting. The number of capillaries surrounding the different fiber types was unchanged after ULLS. Results showed that the adaptive responses of human skeletal muscle to unweighting are qualitatively, but not quantitatively, similar to those of lower mammals and not necessarily dependent on the fiber-type composition.

  9. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Responses to Human Bioeffluents at Levels Recommended by Ventilation Standards

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2017-01-01

    was set to 33 or 4 l/s per person, creating two levels of bioeffluents with carbon dioxide (CO2) at 500 or 1600 ppm. Subjective ratings were collected, cognitive performance was examined and physiological responses were monitored. The results show that exposures to human bioeffluents at ventilation rate...... of 4 l/s per person caused sensory discomfort of visitors, reduced pNN50 (a domain of ECG measurement), but did not produce negative effects on cognitive performance or health symptoms....

  11. Erythropoietin enhances hippocampal response during memory retrieval in humans

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

    2007-01-01

    Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment......) or saline in a between-subjects, double-blind, randomized design. Neural response during picture encoding and retrieval was tested 1 week later. Epo increased hippocampus response during picture retrieval (n = 11) compared with placebo (n = 12; p = 0.04) independent of changes in hematocrit....... This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders....

  12. Monitoring human melanocytic cell responses to piperine using multispectral imaging

    Science.gov (United States)

    Samatham, Ravikant; Phillips, Kevin G.; Sonka, Julia; Yelma, Aznegashe; Reddy, Neha; Vanka, Meenakshi; Thuillier, Philippe; Soumyanath, Amala; Jacques, Steven

    2011-03-01

    Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.

  13. The effect of music on the human stress response.

    Science.gov (United States)

    Thoma, Myriam V; La Marca, Roberto; Brönnimann, Rebecca; Finkel, Linda; Ehlert, Ulrike; Nater, Urs M

    2013-01-01

    Music listening has been suggested to beneficially impact health via stress-reducing effects. However, the existing literature presents itself with a limited number of investigations and with discrepancies in reported findings that may result from methodological shortcomings (e.g. small sample size, no valid stressor). It was the aim of the current study to address this gap in knowledge and overcome previous shortcomings by thoroughly examining music effects across endocrine, autonomic, cognitive, and emotional domains of the human stress response. Sixty healthy female volunteers (mean age = 25 years) were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test: 1) relaxing music ('Miserere', Allegri) (RM), 2) sound of rippling water (SW), and 3) rest without acoustic stimulation (R). Salivary cortisol and salivary alpha-amylase (sAA), heart rate (HR), respiratory sinus arrhythmia (RSA), subjective stress perception and anxiety were repeatedly assessed in all subjects. We hypothesized that listening to RM prior to the stress test, compared to SW or R would result in a decreased stress response across all measured parameters. The three conditions significantly differed regarding cortisol response (p = 0.025) to the stressor, with highest concentrations in the RM and lowest in the SW condition. After the stressor, sAA (p=0.026) baseline values were reached considerably faster in the RM group than in the R group. HR and psychological measures did not significantly differ between groups. Our findings indicate that music listening impacted the psychobiological stress system. Listening to music prior to a standardized stressor predominantly affected the autonomic nervous system (in terms of a faster recovery), and to a lesser degree the endocrine and psychological stress response. These findings may help better understanding the beneficial effects of music on the human body.

  14. The effect of music on the human stress response.

    Directory of Open Access Journals (Sweden)

    Myriam V Thoma

    Full Text Available BACKGROUND: Music listening has been suggested to beneficially impact health via stress-reducing effects. However, the existing literature presents itself with a limited number of investigations and with discrepancies in reported findings that may result from methodological shortcomings (e.g. small sample size, no valid stressor. It was the aim of the current study to address this gap in knowledge and overcome previous shortcomings by thoroughly examining music effects across endocrine, autonomic, cognitive, and emotional domains of the human stress response. METHODS: Sixty healthy female volunteers (mean age = 25 years were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test: 1 relaxing music ('Miserere', Allegri (RM, 2 sound of rippling water (SW, and 3 rest without acoustic stimulation (R. Salivary cortisol and salivary alpha-amylase (sAA, heart rate (HR, respiratory sinus arrhythmia (RSA, subjective stress perception and anxiety were repeatedly assessed in all subjects. We hypothesized that listening to RM prior to the stress test, compared to SW or R would result in a decreased stress response across all measured parameters. RESULTS: The three conditions significantly differed regarding cortisol response (p = 0.025 to the stressor, with highest concentrations in the RM and lowest in the SW condition. After the stressor, sAA (p=0.026 baseline values were reached considerably faster in the RM group than in the R group. HR and psychological measures did not significantly differ between groups. CONCLUSION: Our findings indicate that music listening impacted the psychobiological stress system. Listening to music prior to a standardized stressor predominantly affected the autonomic nervous system (in terms of a faster recovery, and to a lesser degree the endocrine and psychological stress response. These findings may help better understanding the

  15. The Effect of Music on the Human Stress Response

    Science.gov (United States)

    Thoma, Myriam V.; La Marca, Roberto; Brönnimann, Rebecca; Finkel, Linda; Ehlert, Ulrike; Nater, Urs M.

    2013-01-01

    Background Music listening has been suggested to beneficially impact health via stress-reducing effects. However, the existing literature presents itself with a limited number of investigations and with discrepancies in reported findings that may result from methodological shortcomings (e.g. small sample size, no valid stressor). It was the aim of the current study to address this gap in knowledge and overcome previous shortcomings by thoroughly examining music effects across endocrine, autonomic, cognitive, and emotional domains of the human stress response. Methods Sixty healthy female volunteers (mean age = 25 years) were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test: 1) relaxing music (‘Miserere’, Allegri) (RM), 2) sound of rippling water (SW), and 3) rest without acoustic stimulation (R). Salivary cortisol and salivary alpha-amylase (sAA), heart rate (HR), respiratory sinus arrhythmia (RSA), subjective stress perception and anxiety were repeatedly assessed in all subjects. We hypothesized that listening to RM prior to the stress test, compared to SW or R would result in a decreased stress response across all measured parameters. Results The three conditions significantly differed regarding cortisol response (p = 0.025) to the stressor, with highest concentrations in the RM and lowest in the SW condition. After the stressor, sAA (p=0.026) baseline values were reached considerably faster in the RM group than in the R group. HR and psychological measures did not significantly differ between groups. Conclusion Our findings indicate that music listening impacted the psychobiological stress system. Listening to music prior to a standardized stressor predominantly affected the autonomic nervous system (in terms of a faster recovery), and to a lesser degree the endocrine and psychological stress response. These findings may help better understanding the

  16. Behavioral responses associated with a human-mediated predator shelter.

    Directory of Open Access Journals (Sweden)

    Graeme Shannon

    Full Text Available Human activities in protected areas can affect wildlife populations in a similar manner to predation risk, causing increases in movement and vigilance, shifts in habitat use and changes in group size. Nevertheless, recent evidence indicates that in certain situations ungulate species may actually utilize areas associated with higher levels of human presence as a potential refuge from disturbance-sensitive predators. We now use four-years of behavioral activity budget data collected from pronghorn (Antilocapra americana and elk (Cervus elephus in Grand Teton National Park, USA to test whether predictable patterns of human presence can provide a shelter from predatory risk. Daily behavioral scans were conducted along two parallel sections of road that differed in traffic volume--with the main Teton Park Road experiencing vehicle use that was approximately thirty-fold greater than the River Road. At the busier Teton Park Road, both species of ungulate engaged in higher levels of feeding (27% increase in the proportion of pronghorn feeding and 21% increase for elk, lower levels of alert behavior (18% decrease for pronghorn and 9% decrease for elk and formed smaller groups. These responses are commonly associated with reduced predatory threat. Pronghorn also exhibited a 30% increase in the proportion of individuals moving at the River Road as would be expected under greater exposure to predation risk. Our findings concur with the 'predator shelter hypothesis', suggesting that ungulates in GTNP use human presence as a potential refuge from predation risk, adjusting their behavior accordingly. Human activity has the potential to alter predator-prey interactions and drive trophic-mediated effects that could ultimately impact ecosystem function and biodiversity.

  17. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules

    Science.gov (United States)

    Mak, W.C.; Olesen, K.; Sivlér, P.; Lee, C.J.; Moreno-Jimenez, I.; Edin, J.; Courtman, D.; Skog, M.; Griffith, M.

    2015-01-01

    Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line—human umbilical vein endothelial cells (HUVECs). While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation. PMID:26096147

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

    Science.gov (United States)

    da Silva Dantas, Alessandra; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  19. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules

    Directory of Open Access Journals (Sweden)

    W.C. Mak

    2015-06-01

    Full Text Available Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line—human umbilical vein endothelial cells (HUVECs. While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

  20. Approaching threats elicit a freeze-like response in humans.

    Science.gov (United States)

    Sagliano, Laura; Cappuccio, Angela; Trojano, Luigi; Conson, Massimiliano

    2014-02-21

    Freezing is one of the most widely recognized defensive reactions to approaching threats in animals. Here we tested whether the same stimuli can elicit freeze-like responses in healthy humans as well. We used a modified version of the two-frame apparent motion paradigm, in which both size and location of a stimulus within a background were manipulated; by these means, participants perceived the stimuli as approaching or receding. In Experiment 1, we showed that implicitly processed approaching threats (e.g., spiders or snakes) elicited a stronger freeze-like response (operationalized as slower reaction times) with respect to receding threats; freezing was significantly related to higher levels of participants' state anxiety. In Experiment 2, approaching/threatening animals were explicitly judged as more threatening than receding ones. Finally, in two further control experiments we observed that the same manipulation of stimuli's size and location, but in absence of apparent motion, did not affect freezing (Experiment 3) or explicit threat judgements (Experiment 4). The present findings demonstrated that approaching threats are critical to elicit freezing in humans, in line with animals' behaviour. Copyright © 2013. Published by Elsevier Ireland Ltd.

  1. Brain connectivity reflects human aesthetic responses to music.

    Science.gov (United States)

    Sachs, Matthew E; Ellis, Robert J; Schlaug, Gottfried; Loui, Psyche

    2016-06-01

    Humans uniquely appreciate aesthetics, experiencing pleasurable responses to complex stimuli that confer no clear intrinsic value for survival. However, substantial variability exists in the frequency and specificity of aesthetic responses. While pleasure from aesthetics is attributed to the neural circuitry for reward, what accounts for individual differences in aesthetic reward sensitivity remains unclear. Using a combination of survey data, behavioral and psychophysiological measures and diffusion tensor imaging, we found that white matter connectivity between sensory processing areas in the superior temporal gyrus and emotional and social processing areas in the insula and medial prefrontal cortex explains individual differences in reward sensitivity to music. Our findings provide the first evidence for a neural basis of individual differences in sensory access to the reward system, and suggest that social-emotional communication through the auditory channel may offer an evolutionary basis for music making as an aesthetically rewarding function in humans. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Human influenza viruses and CD8(+) T cell responses.

    Science.gov (United States)

    Grant, Emma J; Quiñones-Parra, Sergio M; Clemens, E Bridie; Kedzierska, Katherine

    2016-02-01

    Influenza A viruses (IAVs) cause significant morbidity and mortality worldwide, despite new strain-specific vaccines being available annually. As IAV-specific CD8(+) T cells promote viral control in the absence of neutralizing antibodies, and can mediate cross-reactive immunity toward distinct IAVs to drive rapid recovery from both mild and severe influenza disease, there is great interest in developing a universal T cell vaccine. However, despite detailed studies in mouse models of influenza virus infection, there is still a paucity of data on human epitope-specific CD8(+) T cell responses to IAVs. This review focuses on our current understanding of human CD8(+) T cell immunity against distinct IAVs and discusses the possibility of achieving a CD8(+) T cell mediated-vaccine that protects against multiple, distinct IAV strains across diverse human populations. We also review the importance of CD8(+) T cell immunity in individuals highly susceptible to severe influenza infection, including those hospitalised with influenza, the elderly and Indigenous populations. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Human Responses to Climate Variability: The Case of South Africa

    Science.gov (United States)

    Oppenheimer, M.; Licker, R.; Mastrorillo, M.; Bohra-Mishra, P.; Estes, L. D.; Cai, R.

    2014-12-01

    Climate variability has been associated with a range of societal and individual outcomes including migration, violent conflict, changes in labor productivity, and health impacts. Some of these may be direct responses to changes in mean temperature or precipitation or extreme events, such as displacement of human populations by tropical cyclones. Others may be mediated by a variety of biological, social, or ecological factors such as migration in response to long-term changes in crops yields. Research is beginning to elucidate and distinguish the many channels through which climate variability may influence human behavior (ranging from the individual to the collective, societal level) in order to better understand how to improve resilience in the face of current variability as well as future climate change. Using a variety of data sets from South Africa, we show how climate variability has influenced internal (within country) migration in recent history. We focus on South Africa as it is a country with high levels of internal migration and dramatic temperature and precipitation changes projected for the 21st century. High poverty rates and significant levels of rain-fed, smallholder agriculture leave large portions of South Africa's population base vulnerable to future climate change. In this study, we utilize two complementary statistical models - one micro-level model, driven by individual and household level survey data, and one macro-level model, driven by national census statistics. In both models, we consider the effect of climate on migration both directly (with gridded climate reanalysis data) and indirectly (with agricultural production statistics). With our historical analyses of climate variability, we gain insights into how the migration decisions of South Africans may be influenced by future climate change. We also offer perspective on the utility of micro and macro level approaches in the study of climate change and human migration.

  4. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  5. Disparity-tuned population responses from human visual cortex.

    Science.gov (United States)

    Cottereau, Benoit R; McKee, Suzanne P; Ales, Justin M; Norcia, Anthony M

    2011-01-19

    We used source imaging of visual evoked potentials to measure neural population responses over a wide range of horizontal disparities (0.5-64 arcmin). The stimulus was a central disk that moved back and forth across the fixation plane at 2 Hz, surrounded either by binocularly uncorrelated dots (disparity noise) or by correlated dots presented in the fixation plane. Both disk and surround were composed of dynamic random dots to remove coherent monocular information. Disparity tuning was measured in five visual regions of interest (ROIs) [V1, human middle temporal area (hMT+), V4, lateral occipital complex (LOC), and V3A], defined in separate functional magnetic resonance imaging scans. The disparity tuning functions peaked between 2 and 16 arcmin for both types of surround in each ROI. Disparity tuning in the V1 ROI was unaffected by the type of surround, but surround correlation altered both the amplitude and phase of the disparity responses in the other ROIs. Response amplitude increased when the disk was in front of the surround in the V3A and LOC ROIs, indicating that these areas encode figure-ground relationships and object convexity. The correlated surround produced a consistent phase lag at the second harmonic in the hMT+ and V4 ROIs without a change in amplitude, while in the V3A ROI, both phase and amplitude effects were observed. Sensitivity to disparity context is thus widespread in visual cortex, but the dynamics of these contextual interactions differ across regions.

  6. Health and Human Rights: New challenges for social responsiveness

    Directory of Open Access Journals (Sweden)

    Leslie London

    2009-11-01

    . Finally, it is shown how the portfolio of social responsiveness activities in the health and human rights envelope has offered significant and novel mutual benefits to the University and the community.

  7. Animal and human responses to UVA and UVB[UV; Skin; Eye; Carcinogenesis; Immune response

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, R.; Cridland, N.; Kowalczuk, C

    1997-12-01

    Ultraviolet radiation (UVR) comprises the most energetic region of the optical radiation spectrum and is able to induce photochemical changes in the superficial tissues of animals and people which can lead to various acute or chronic adverse health effects. The evidence concerning experimental studies of animals and, where available, volunteers of the effects of occupationally relevant wavelengths (principally UVB, 280-315 rim, and UVA, 315-400 nm) has been reviewed. Experimental studies on animals indicate that exposure to UVR elicits transient (acute) and long-lasting (chronic) effects in the skin and the eye, the severity of which increases in proportion to the exposure. Transient responses have also been investigated in human volunteers and these include adaptive changes such as immediate pigment darkening, melanogenesis and epidermal hyperplasia, and inflammatory responses such as erythema in the skin and keratitis and conjunctivitis in the eye. Irreversible, long-lasting changes also occur following exposure; these include photoageing of the skin, and the development of cataracts in the lens of the eye. Animal studies show that UVR can act either as a complete carcinogen, capable of inducing tumours when applied by itself, or as a co-carcinogen acting in combination with tumour initiators and promoters. The interaction of UVR with the immune system is complex. Exposure to UVR affects the immune system, depressing certain types of cell-mediated antigen-specific responses. Variable immunosuppressive effects have also been reported in humans. In addition, exogenous chemical sensitisers can initiate phototoxic or photoallergic responses in humans and animals; these can precede the development of more persistent idiopathic photodermatoses in which the sensitiser may be an endogenous chemical or antigen. Recommendations for further research are made. (author)

  8. Simulating Physiological Response with a Passive Sensor Manikin and an Adaptive Thermal Manikin to Predict Thermal Sensation and Comfort

    Energy Technology Data Exchange (ETDEWEB)

    Rugh, John P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Chaney, Larry [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hepokoski, Mark [ThermoAnalytics Inc.; Curran, Allen [ThermoAnalytics Inc.; Burke, Richard [Measurement Technology NW; Maranville, Clay [Ford Motor Company

    2015-04-14

    Reliable assessment of occupant thermal comfort can be difficult to obtain within automotive environments, especially under transient and asymmetric heating and cooling scenarios. Evaluation of HVAC system performance in terms of comfort commonly requires human subject testing, which may involve multiple repetitions, as well as multiple test subjects. Instrumentation (typically comprised of an array of temperature sensors) is usually only sparsely applied across the human body, significantly reducing the spatial resolution of available test data. Further, since comfort is highly subjective in nature, a single test protocol can yield a wide variation in results which can only be overcome by increasing the number of test replications and subjects. In light of these difficulties, various types of manikins are finding use in automotive testing scenarios. These manikins can act as human surrogates from which local skin and core temperatures can be obtained, which are necessary for accurately predicting local and whole body thermal sensation and comfort using a physiology-based comfort model (e.g., the Berkeley Comfort Model). This paper evaluates two different types of manikins, i) an adaptive sweating thermal manikin, which is coupled with a human thermoregulation model, running in real-time, to obtain realistic skin temperatures; and, ii) a passive sensor manikin, which is used to measure boundary conditions as they would act on a human, from which skin and core temperatures can be predicted using a thermophysiological model. The simulated physiological responses and comfort obtained from both of these manikin-model coupling schemes are compared to those of a human subject within a vehicle cabin compartment transient heat-up scenario.

  9. Response of human populations to large-scale emergencies

    Science.gov (United States)

    Bagrow, James; Wang, Dashun; Barabási, Albert-László

    2010-03-01

    Until recently, little quantitative data regarding collective human behavior during dangerous events such as bombings and riots have been available, despite its importance for emergency management, safety and urban planning. Understanding how populations react to danger is critical for prediction, detection and intervention strategies. Using a large telecommunications dataset, we study for the first time the spatiotemporal, social and demographic response properties of people during several disasters, including a bombing, a city-wide power outage, and an earthquake. Call activity rapidly increases after an event and we find that, when faced with a truly life-threatening emergency, information rapidly propagates through a population's social network. Other events, such as sports games, do not exhibit this propagation.

  10. Mu suppression and human movement responses to the Rorschach test.

    Science.gov (United States)

    Pineda, Jaime A; Giromini, Luciano; Porcelli, Piero; Parolin, Laura; Viglione, Donald J

    2011-03-30

    Electroencephalographic μ wave suppression was investigated using all 10 static, ambiguous Rorschach stimuli. In an earlier study using four Rorschach stimuli, the two stimuli that elicited feelings of movement were associated with μ suppression. In this study, we replicated this relationship using all 10 Rorschach stimuli while overcoming a number of other earlier limitations. The results strongly support the hypothesis that internal representation of the feeling of movement is sufficient to suppress the μ rhythm even when minimal external cues are present. This outcome increases the generalizability and ecological validity of this approach and gives support to the traditional interpretation of the Rorschach human movement responses as being associated with cognitive functioning, empathy, and social cognition.

  11. Incorporating Human Rights into the Sustainability Agenda: A Commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It"

    Science.gov (United States)

    Andrew, Jane

    2013-01-01

    In her commentary of McPhail's 2013 article "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It: Incorporating Human Rights into the Sustainability Agenda," Jane Andrew begins by highlighting a number of McPhail's primary arguments. She points out that McPhail sets out to achieve two things…

  12. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models.

    Directory of Open Access Journals (Sweden)

    Fang Peng

    Full Text Available BACKGROUND: Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently "normalize" the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar can create a "vascular normalization window" to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC in mice. METHODOLOGY/PRINCIPAL FINDINGS: Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5-8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohistochemical staining. During endostar treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Hypoxic tumor cell fraction also decreased after the treatment. The transient modulation of tumor physiology caused by endostar improved the effect of radiation treatment compared with other treatment schedules. The expressions of vascular endothelial growth factor (VEGF, matrix metalloproteinase-2 (MMP-2, MMP-9, and MMP-14 decreased, while the level of pigment epithelium-derived factor (PEDF increased. CONCLUSIONS: Endostar normalized tumor vasculature, which alleviated hypoxia and significantly sensitized the function of radiation in anti-tumor in human NPC. The results provide an important experimental basis for combining endostar with radiation therapy in human NPC.

  13. The response of meiofauna to human trampling on coral reefs

    Directory of Open Access Journals (Sweden)

    Visnu C. Sarmento

    2011-04-01

    Full Text Available Coastal environments are trampled by humans worldwide; however, there are few studies that evaluate the effect of trampling on the meiofauna of hard substrates, and none on meiofauna of reef environments. We investigated the effects of trampling due to tourism on the meiofauna of reef formations on the northeastern coast of Brazil. Samples were taken from five paired stations located in two areas on the reef: an area protected since 2004, and an area open to tourist visits. Trampling caused important changes in the meiofaunal assemblage. The densities of the total meiofauna and of the commonest groups were negatively affected in the trampled area. Among the major groups, Polychaeta proved to be very sensitive to this disturbance. The meiofauna groups showed different response patterns to trampling depending on the species of algae trampled. Reductions in animal densities were partly attributed to the loss of turf biomass and associated sand caused by trampling, and partly to the direct effect of people stepping on the animals. Considering the importance of meiofauna in the food web as well as its biodiversity, these results highlight the possible negative effects of human trampling on the ecological and economic “services” that coral reefs provide.

  14. Human balance responses to perturbations in the horizontal plane.

    Science.gov (United States)

    Fritschi, Michael; Jelinek, Herbert F; McGloughlin, Tim; Khalaf, Kinda; Khandoker, Ahsan H; Vallery, Heike

    2014-01-01

    Human balance strategies during standing have been studied extensively. Most of these studies rely on perturbations to the feet, for example by moving platforms or treadmills, and focus on the sagittal plane. Less research has been done on reactions to perturbations to the upper body, and the direction dependence of stabilizing strategies is still an open question. Here, we describe an experiment where we apply horizontal static pulling forces to the upper body of standing human subjects in different directions by means of an overhead robotic device, the FLOAT. Based on a simplified mechanical model, we propose the normalized displacement of the center of pressure, the ΔCoPn, as a measure of the selected balance strategy. We find that existing neuromechanical models do not fully explain responses to these static horizontal forces, because they predict too much CoP movement. Further, we found a tendency to particularly reduce CoP movement in anterior-posterior direction, indicating that reconfiguration of the body may play a larger role in this direction.

  15. The suppression of innate immune response by human rhinovirus C.

    Science.gov (United States)

    Pang, Li-Li; Yuan, Xin-Hui; Shao, Chang-Sheng; Li, Mao-Zhong; Wang, Ying; Wang, Hui-Min; Xie, Guang-Cheng; Xie, Zhi-Ping; Yuan, Yue; Zhou, Dong-Mei; Sun, Xiao-Man; Zhang, Qing; Xin, Yan; Li, Dan-di; Duan, Zhao-Jun

    2017-08-12

    Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-β activation was ascribed to 3C(pro) of RV-C, and the 40-His site of 3C(pro) played an important role. Furthermore, RIG-I was degraded by 3C(pro) in a caspase-dependent manner and 3C(pro) cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells. Copyright © 2017. Published by Elsevier Inc.

  16. Lactic acid delays the inflammatory response of human monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peter, Katrin, E-mail: katrin.peter@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Rehli, Michael, E-mail: michael.rehli@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Singer, Katrin, E-mail: katrin.singer@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Renner-Sattler, Kathrin, E-mail: kathrin.renner-sattler@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Kreutz, Marina, E-mail: marina.kreutz@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany)

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

  17. Human cell-mediated immune responses to chlamydial antigens.

    Science.gov (United States)

    Hanna, L; Schmidt, L; Sharp, M; Stites, D P; Jawetz, E

    1979-02-01

    A reproducible method was developed to determine the ability of chlamydial antigens to stimulate lymphocytes from volunteers. In tests repeated 4 to 14 times, the cells from a given volunteer gave a relatively narrow range of responses, but there were great differences in the mean response of different volunteers. In the entire group of 52 volunteers, lymphocyte stimulation was significantly associated with the presence of antibody, but in a given individual results of one test did not aid in predicting the results of the other. A majority of persons with either antichlamydial antibody or elevated lymphocyte stimulation, or both, did not have a history of signs or symptoms within a spectrum of chlamydial diseases. This may reflect the great frequency of asymptomatic infection with these organisms. The lymphocytes of some individuals were stimulated to a significantly greater degree by antigens of one chlamydial species (Chlamydia trachomatis or C. psittaci) than by the other. These and other cell-mediated reactions in human chlamydial infections, and their possible medical significance, are under continued study.

  18. Gustatory and olfactory responses to stimulation of the human insula.

    Science.gov (United States)

    Mazzola, Laure; Royet, Jean-Pierre; Catenoix, Hélène; Montavont, Alexandra; Isnard, Jean; Mauguière, François

    2017-09-01

    Despite numerous studies suggesting the role of insular cortex in the processing of gustatory and olfactory inputs, the exact location of olfactogustatory representation in the insula remains controversial. Here we provide a functional mapping of olfactory-gustatory responses to stimulation of the human insular cortex. We reviewed 651 electrical stimulations of the insula that were performed in 221 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory epilepsy. Gustatory sensations were evoked in 15 (2.7%) of the 550 stimulations that elicited a clinical response. They were exclusively obtained after stimulation of a relatively delimited zone of insula, located in its mid-dorsal part (posterior short gyrus). Six olfactory sensations (1.1%) could be obtained during stimulations of an insular region that partially overlapped with the gustatory representation. Our study provides a functional mapping of gustatory representation in the insular posterior short gyrus and the first detailed description of olfactory sensations obtained by direct stimulation of mid-dorsal insula. Our data also show a spatial overlap between gustatory, olfactory, and oral somatosensory representation in the mid-dorsal insula, and suggest that this part of the insula may be an integrated oral sensory region that plays a key role in flavor perception. It also indicates that dysfunction in this region should be considered during the evaluation of gustatory and olfactory epileptic seizures. Ann Neurol 2017;82:360-370. © 2017 American Neurological Association.

  19. Peripheral chemoreceptor responsiveness and hypoxic pulmonary vasoconstriction in humans.

    Science.gov (United States)

    Albert, Tyler J; Swenson, Erik R

    2014-04-01

    Studies in animals have shown that interruption of carotid body afferent hypoxic signaling or efferent CNS activity to the lung enhances hypoxic pulmonary vasoconstriction (HPV). Whether a similar influence of the CNS on HPV strength is present in humans has never been studied, owing to the invasive nature of physical neural ablation or nonspecific systemic effects of pharmacological blockade of putative neural pathways. In order to demonstrate a peripheral chemoreceptor-mediated modulation of HPV in man, we hypothesized that individuals with high hypoxic ventilatory responsiveness, indicative of strong peripheral hypoxic chemosensitivity, should have less HPV in response to inspired hypoxia. In 15 healthy men and women, we measured the normobaric poikilocapnic hypoxic ventilatory response (HVR; L min(-1) % SPo2(-1)) during 15 min of hypoxia (FIo2=0.12). On the following day, we then measured pulmonary artery systolic pressure (PASP) using echosonography while subjects randomly breathed 0.21, 0.18, 0.15, and 0.12 FIo2, each for periods of 15 min. We chose this strategy to obtain an equivalent stimulus for HPV in all subjects, using SPo2 as a surrogate for alveolar Po2. HPV was assessed as PASP at a common interpolated arterial oxygen saturation (SPo2) of 85%. We recorded a sufficient six-fold range of HVR (0.05-0.30, mean 0.13 L min(-1) % SPo2(-1)) similar to previously published data on normobaric, poikilocapnic HVR. HPV at SPo2 of 85% was 28.5 mmHg (range 21.7-41.3). There was a significant inverse relationship between poikilocapnic HVR and HPV (p=0.006, R(2)=0.38). Previous studies of individuals with susceptibility to high altitude pulmonary edema (HAPE) have suggested that both low HVR and high HPV are important risk factors. We show that these two responses are inversely correlated and conclude that a greater magnitude of peripheral chemoreceptor response to hypoxia limits hypoxic pulmonary vasoconstriction in healthy subjects.

  20. What does it mean to be human? How salience of the human category affects responses to intergroup harm

    NARCIS (Netherlands)

    Morton, T.A; Postmes, T.

    2011-01-01

    Two studies explore how salience of the human category influences responses to intergroup harm and how different images of humanity modify these effects. In Study 1, British participants (n = 86) contemplated acts of terrorism against their group. When the human category (versus intergroup

  1. Nanoparticle-allergen interactions mediate human allergic responses: protein corona characterization and cellular responses.

    Science.gov (United States)

    Radauer-Preiml, Isabella; Andosch, Ancuela; Hawranek, Thomas; Luetz-Meindl, Ursula; Wiederstein, Markus; Horejs-Hoeck, Jutta; Himly, Martin; Boyles, Matthew; Duschl, Albert

    2016-01-16

    Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule 'corona'. Hence, the 'corona' defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. Therefore, the aim of this present study was to gain an insight into the interactions of gold nanoparticles with different seasonally and perennially occurring outdoor and indoor allergens. Gold nanoparticles (AuNPs) were conjugated with the major allergens of birch pollen (Bet v 1), timothy grass pollen (Phl p 5) and house dust mite (Der p 1). The AuNP-allergen conjugates were characterized by means of TEM negative staining, dynamic light scattering (DLS), z-potential measurements and hyperspectral imaging. Furthermore, 3D models were constructed, based on the characterization data, to visualize the interaction between the allergens and the AuNPs surface. Differences in the activation of human basophil cells derived from birch/grass pollen- and house dust mite-allergic patients in response to free allergen and AuNP-allergen conjugates were determined using the basophil activation assay (BAT). Potential allergen corona replacement during BAT was controlled for using Western blotting. The protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was assessed, by an enzymatic activity assay and a cellular assay pertaining to lung type II alveolar epithelial cell tight junction integrity. The formation of a stable corona was found for all three allergens used. Our data suggest, that depending on the allergen, different effects are observed after binding to ENMs, including enhanced allergic responses against Der p 1 and also, for some patients, against Bet v 1. Moreover elevated

  2. Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells.

    Directory of Open Access Journals (Sweden)

    Devi Rajan

    Full Text Available Infections with human rhinovirus (HRV are commonly associated with acute upper and lower respiratory tract disease and asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors that contribute to pathogenesis. Since species A HRVs are often associated with more serious HRV disease than species B HRVs, differences in immune responses they induce should inform disease pathogenesis. To identify species differences in induced responses, we evaluated 3 species A viruses, HRV 25, 31 and 36 and 3 species B viruses, HRV 4, 35 and 48 by exposing human PBMCs to HRV infected Calu-3 cells. To evaluate the potential effect of memory induced by previous HRV infection on study responses, we tested cord blood mononuclear cells that should be HRV naïve. There were HRV-associated increases (significant increase compared to mock-infected cells for one or more HRVs for IP-10 and IL-15 that was unaffected by addition of PBMCs, for MIP-1α, MIP-1β, IFN-α, and HGF only with addition of PBMCs, and for ENA-78 only without addition of PBMCs. All three species B HRVs induced higher levels, compared to A HRVs, of MIP-1α and MIP-1β with PBMCs and ENA-78 without PBMCs. In contrast, addition of CBMCs had less effect and did not induce MIP-1α, MIP-1β, or IFN-α nor block ENA-78 production. Addition of CBMCs did, however, increase IP-10 levels for HRV 35 and HRV 36 infection. The presence of an effect with PBMCs and no effect with CBMCs for some responses suggest differences between the two types of cells possibly because of the presence of HRV memory responses in PBMCs and not CBMCs or limited response capacity for the immature CBMCs relative to PBMCs. Thus, our results indicate that different HRV strains can induce different patterns of cytokines and chemokines; some of these differences may be due to differences in memory responses induced by past HRV infections, and other differences

  3. Human placenta-derived adherent cells induce tolerogenic immune responses

    Science.gov (United States)

    Liu, Wei; Morschauser, Andrew; Zhang, Xin; Lu, Xiaohua; Gleason, Joseph; He, Shuyang; Chen, Hong-Jung; Jankovic, Vladimir; Ye, Qian; Labazzo, Kristen; Herzberg, Uri; Albert, Vivian R; Abbot, Stewart E; Liang, Bitao; Hariri, Robert

    2014-01-01

    Human placenta-derived adherent cells (PDAC cells) are a culture expanded, undifferentiated mesenchymal-like population derived from full-term placental tissue, with immunomodulatory and anti-inflammatory properties. PDA-001 (cenplacel-L), an intravenous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and inflammatory diseases. To elucidate the mechanisms underlying the immunoregulatory properties of PDAC cells, we investigated their effects on immune cell populations, including T cells and dendritic cells (DC) in vitro and in vivo. PDAC cells suppressed T-cell proliferation in an OT-II T-cell adoptive transfer model, reduced the severity of myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis and ameliorated inflammation in a delayed type hypersensitivity response model. In vitro, PDAC cells suppressed T-cell proliferation and inhibited Th1 and Th17 differentiation. Analysis of tissues derived from PDAC cell-treated animals revealed diminished CD86 expression on splenic DC, suggesting that they can also modulate DC populations. Furthermore, PDAC cells modulate the differentiation and maturation of mouse bone marrow-derived DC. Similarly, human DC differentiated from CD14+ monocytes in the presence of PDAC cells acquired a tolerogenic phenotype. These tolerogenic DC failed to induce allogeneic T-cell proliferation and differentiation toward Th1, but skewed T-cell differentiation toward Th2. Inhibition of cyclo-oxygenase-2 activity resulted in a significant, but not complete, abrogation of PDAC cells' effects on DC phenotype and function, implying a role for prostaglandin E2 in PDAC-mediated immunomodulation. This study identifies modulation of DC differentiation toward immune tolerance as a key mechanism underlying the immunomodulatory activities of PDAC cells. PMID:25505962

  4. Lactic acid delays the inflammatory response of human monocytes.

    Science.gov (United States)

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Human Rights, Mineral Rights and Corporate Social Responsibility ...

    African Journals Online (AJOL)

    The Paper outlines the various human rights and mineral rights in Ghana and the effects of mining on human rights. It establishes that although the Constitution of Ghana guarantees social, economic, cultural and other human rights, mining operations continue to affect human rights as if these laws did not exist. The Paper ...

  6. The evolution of predictive adaptive responses in human life history.

    Science.gov (United States)

    Nettle, Daniel; Frankenhuis, Willem E; Rickard, Ian J

    2013-09-07

    Many studies in humans have shown that adverse experience in early life is associated with accelerated reproductive timing, and there is comparative evidence for similar effects in other animals. There are two different classes of adaptive explanation for associations between early-life adversity and accelerated reproduction, both based on the idea of predictive adaptive responses (PARs). According to external PAR hypotheses, early-life adversity provides a 'weather forecast' of the environmental conditions into which the individual will mature, and it is adaptive for the individual to develop an appropriate phenotype for this anticipated environment. In internal PAR hypotheses, early-life adversity has a lasting negative impact on the individual's somatic state, such that her health is likely to fail more rapidly as she gets older, and there is an advantage to adjusting her reproductive schedule accordingly. We use a model of fluctuating environments to derive evolveability conditions for acceleration of reproductive timing in response to early-life adversity in a long-lived organism. For acceleration to evolve via the external PAR process, early-life cues must have a high degree of validity and the level of annual autocorrelation in the individual's environment must be almost perfect. For acceleration to evolve via the internal PAR process requires that early-life experience must determine a significant fraction of the variance in survival prospects in adulthood. The two processes are not mutually exclusive, and mechanisms for calibrating reproductive timing on the basis of early experience could evolve through a combination of the predictive value of early-life adversity for the later environment and its negative impact on somatic state.

  7. Pharmacokinetics and leukocyte responses of recombinant human interleukin-10.

    Science.gov (United States)

    Radwanski, E; Chakraborty, A; Van Wart, S; Huhn, R D; Cutler, D L; Affrime, M B; Jusko, W J

    1998-12-01

    To study the pharmacokinetics and ex vivo leukocyte responses of recombinant human IL-10 (rHuIL-10) following single s.c. and i.v. dosing. A randomized two-way cross-over study was undertaken in 17 healthy volunteers in which rHuIL-10 was administered as 25 microg/kg s.c. and i.v. doses. Blood samples were collected for 48 hr after dosing to determine serum IL-10 concentrations. Inhibitory activity of IL-10 on ex vivo production of inflammatory cytokines (TNF-alpha and IL-1beta) by LPS-treated peripheral blood cells were measured over 96 hr. A physiologically-relevant modeling approach was developed to determine the pharmacokinetics for two routes of administration (s.c. and i.v.). The i.v. dose showed polyexponential disposition with CL of 65 mL/kg/hr, Vss of 70 mL/kg, and t1/2 of 1.94 hr. Absolute bioavailability averaged 42% for s.c. dosing which produced lower but sustained concentrations. Substantial and prolonged suppression of TNF-alpha and IL-1beta production was achieved during IL-10 treatment. The Hill Function was used to account for the joint concentration-dependent immunosuppressive action of rHuIL-10 after both i.v. and s.c. doses. The IC50 values were about 0.03 ng/ml and Imax values were about 0.85 for both TNF-alpha and IL-1beta suppression. The degree of change as well as the duration of leukocyte response was greater after s.c. administration than after i.v. administration. rHuIL-10 shows favorable PKPD characteristics especially by the s.c. route of administration which produced prolonged suppression of cytokine production (ex vivo) which may be applicable in various immune-related disorders.

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

    Directory of Open Access Journals (Sweden)

    Kandhasamy Sowndhararajan

    2016-11-01

    Full Text Available 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

  9. Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology.

    Science.gov (United States)

    Sharma, Anurag; Wu, Wenzhu; Sung, Biin; Huang, Jing; Tsao, Tiffany; Li, Xiangming; Gomi, Rika; Tsuji, Moriya; Worgall, Stefan

    2016-05-15

    Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4(+) T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1β (IL-1β) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. Infections with respiratory syncytial virus (RSV) are common and can cause severe lung disease in infants and the elderly. The lack of a suitable animal model with disease features similar to those in humans has hampered efforts to predict the efficacy of novel anti-RSV therapies and vaccines for use in

  10. Human mRNA response to exercise and temperature.

    Science.gov (United States)

    Slivka, D R; Dumke, C L; Tucker, T J; Cuddy, J S; Ruby, B

    2012-02-01

    The purpose of this research was to determine the mRNA response to exercise in different environmental temperatures. 9 recreationally active males (27±1 years, 77.4±2.7  kg, 13.5±1.5% fat, 4.49±0.15  L · min (-1) VO2 max) completed 3 trials consisting of 1 h cycling exercise at 60% Wmax followed by a 3 h recovery in the cold (7°C), room temperature (20°C), and hot (33°C) environments. Muscle biopsies were obtained pre, post, and 3 h post exercise for the analysis of glycogen and mRNA. Expired gases were collected to calculate substrate use. PGC-1α increased to a greater degree in the cold trial than in the room temperature trial (p=0.036) and the hot trial (p=0.006). PGC1-α mRNA was also higher after the room temperature trial than the hot trial (p=0.050). UCP3 and MFN2 mRNA increased with exercise (pcold than exercise in the heat. However, VO2 was higher during recovery in the cold trial than in the room temperature and hot trials (p<0.05). This study presents evidence of PGC-1α temperature sensitivity in human skeletal muscle. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS.

    Science.gov (United States)

    Hwang, Shen-An; Kruzel, Marian L; Actor, Jeffrey K

    2016-12-01

    Lactoferrin, an iron-binding glycoprotein found in mammalian mucosal secretions and granules of neutrophils, possesses several immune modulatory properties. Published reports indicate that lactoferrin enhances the efficacy of the tuberculosis vaccine, BCG (Bacillus Calmette Guerin), both by increasing macrophage and dendritic cell ability to stimulate receptive T cells and by modulating the inflammatory response. This report is the first to demonstrate the effects of a recombinant human lactoferrin (10 μg/mL) on human PBMC derived CD14+ and CD16+ macrophages stimulated with a strong (LPS, 10 ng/mL) or weaker (BCG, MOI 1:1) stimulator of inflammation. After 3 days culture, LPS and human lactoferrin treated CD14+ cells significantly increased production of IL-10, IL-6, and MCP-1 compared to the LPS only group. In contrast, similarly treated CD16+ macrophages increased production of IL-12p40 and IL-10 and decreased TNF-α. Limited changes were observed in BCG stimulated CD14+ and CD16+ macrophages with and without lactoferrin. Analysis of surface expression of antigen presentation and co-stimulatory molecules demonstrated that CD14+ macrophages, when stimulated with BCG or LPS and cultured with lactoferrin, increased expression of CD86. CD16+ macrophages treated with lactoferrin showed a similar trend of increase in CD86 expression, but only when stimulated with BCG. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  13. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.

    2011-01-01

    For the evaluation of impact scenarios with a substantial vertical component, the performance of current human surrogates - the RID 3D hardware dummy and two numerical human models - was evaluated. Volunteer tests with 10G and 6G pulses were compared to reconstructed tests with human surrogates.

  14. Reindeer and caribou (Rangifer tarandus response towards human activities

    Directory of Open Access Journals (Sweden)

    Eigil Reimers

    2009-01-01

    Full Text Available We address the question of how human activities and infrastructure influence reindeer/caribou’s (Rangifer tarandus behaviour and habitat use and review studies based on current methodologies. Anthropogenic activities have a direct affect on Rangifer behaviour through the senses hearing, sight and smell, and all of these are important tools for behavioural risk assessment. Short term indirect responses, such as habituation, sensitisation, avoidance, and displacement, develop through neutral, positive or negative associations towards stimulus in terms of Rangifer’s ability to experience, learn, and remember. Long term behavioural responses develop through interaction with predators and, for reindeer, also domestication. A survey of the literature dealing with behavioural studies reveals that although Rangifer in most cases retreat from anthropogenic activities, comfort distances (i.e. distances beyond which animal behaviour or activity are not influenced are relatively short. In most cases, energetic implications appear moderate and small compared to other natural, biotic influences such as disturbance (and death caused by insect and/or predator harassment. Unless obstructing access, physical constructions of various kinds apparently have limited effects on Rangifer behaviour or habitat use. On the other hand, constructions that do obstruct or limit access and recreational or other motorized and non-motorized activities appear to have stronger impacts on avoidance and redistribution of Rangifer. Behavioural effects that might decrease survival and reproduction include retreat from favourable habitat near disturbance sources and reduction of time spent feeding with resulting energy depletion over time. Rangifer habitat use, habitat avoidance, and feeding preferences are governed by a complexity of natural interacting factors. Domestication, habituation and sensitisation are essential in shaping Rangifer’s adaptability, and should be included

  15. Human Adaptation Genetic Response Suites: Toward New Interventions and Countermeasures for Spaceflight

    Science.gov (United States)

    Sundaresan, A.; Pellis, N. R.

    2005-01-01

    Genetic response suites in human lymphocytes in response to microgravity are important to identify and further study in order to augment human physiological adaptation to novel environments. Emerging technologies, such as DNA micro array profiling, have the potential to identify novel genes that are involved in mediating adaptation to these environments. These genes may prove to be therapeutically valuable as new targets for countermeasures, or as predictive biomarkers of response to these new environments. Human lymphocytes cultured in lg and microgravity analog culture were analyzed for their differential gene expression response. Different groups of genes related to the immune response, cardiovascular system and stress response were then analyzed. Analysis of cells from multiple donors reveals a small shared set that are likely to be essential to adaptation. These three groups focus on human adaptation to new environments. The shared set contains genes related to T cell activation, immune response and stress response to analog microgravity.

  16. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    Directory of Open Access Journals (Sweden)

    King Nicholas JC

    2006-05-01

    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  17. Predicting Metapopulation Responses To Conservation In Human-Dominated Landscapes

    Directory of Open Access Journals (Sweden)

    Zachary S. Ladin

    2016-10-01

    Full Text Available Loss of habitat to urbanization is a primary cause of population declines as human-dominated landscapes expand at increasing rates. Understanding how the relative effects of different conservation strategies is important to slow population declines for species in urban landscapes. We studied the wood thrush Hylocichla mustelina, a declining forest-breeding Neotropical migratory species, and umbrella species for forest-breeding songbirds, within the urbanized mid-Atlantic United States. We integrated 40 years of demographic data with contemporary metapopulation model simulations of breeding wood thrushes to predict population responses to differing conservation scenarios. We compared four conservation scenarios over a 30-year time period (2014–2044 representing A current observed state (Null, B replacing impervious surface with forest (Reforest, C reducing brown-headed cowbird Molothrus ater parasitism pressure (Cowbird removal, and D simultaneous reforesting and cowbird removal. Compared to the Null scenario, the Reforest scenario increased mean annual population trends by 54 % , the Remove cowbirds scenario increased mean annual population trends by 38 %, and the scenario combining reforestation and cowbird removal increased mean annual population trends by 98 %. Mean annual growth rates (λ per site were greater in the Reforest (λ = 0.94 and Remove cowbirds (λ = 0.92 compared to the Null (λ = 0.88 model scenarios. However, only by combining the positive effects of reforestation and cowbird removal did wood thrush populations stop declining (λ = 1.00. Our results suggest that independently replacing impervious surface with forest habitat around forest patches and removing cowbirds may slow current negative population trends. Furthermore, conservation efforts that combine reforestation and cowbird removal may potentially benefit populations of wood thrushes and other similarly forest-breeding songbird species within urbanized fragmented

  18. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun [Division of heavy ion clinical research, Korea University, Seoul (Korea, Republic of); Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2012-11-15

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy.

  19. Passive biaxial mechanical response of aged human iliac arteries.

    Science.gov (United States)

    Schulze-Bauer, Christian A J; Mörth, Christian; Holzapfel, Gerhard A

    2003-06-01

    Inflation and extension tests of arteries are essential for the understanding of arterial wall mechanics. Data for such tests of human arteries are rare. At autopsy we harvested 10 non-diseased external iliac arteries of aged subjects (52-87 yrs). Structural homogeneity was ensured by means of ultrasound imaging, and anamneses of patients were recorded. We measured the axial in situ stretches, load-free geometries and opening angles. Passive biaxial mechanical responses of preconditioned cylindrical specimens were studied in 37 degrees C calcium-free Tyrode solution under quasistatic loading conditions. Specimens were subjected to pressure cycles varying from 0 to 33.3 kPa (250 mmHg) at nine fixed axial loads, varying from 0 to 9.90N. For the description of the load-deformation behavior we employed five "two-dimensional" orthotropic strain-energy functions frequently used in arterial wall mechanics. The associated constitutive models were compared in regard to their ability of representing the experimental data. Histology showed that the arteries were of the muscular type. In contrast to animal arteries they exhibited intimal layers of considerable thickness. The average ratio of wall thickness to outer diameter was 7.7, which is much less than observed for common animal arteries. We found a clear correlation between age and the axial in situ stretch lambda is (r = -0.72, P = 0.03), and between age and distensibility of specimens, i.e. aged specimens are less distensible. Axial in situ stretches were clearly smaller (1.07 +/- 0.09, mean +/- SD) than in animal arteries. For one specimen lambda is was even smaller than 1.0, i.e. the vessel elongated axially upon excision. The nonlinear and anisotropic load-deformation behavior showed small hystereses. For the majority of specimens we observed axial stretches smaller than 1.3 and circumferential stretches smaller than 1.1 for the investigated loading range. Data from in situ inflation tests showed a significant

  20. Legal response to human rights challenges of multinational ...

    African Journals Online (AJOL)

    The duty to protect human rights is no longer the sole duty of states but also that of other parties like the multinational corporations, companies and business enterprises which are all part of the private sector. This is because it has been observed that this sector, particularly multinational corporations also violate human ...

  1. Human-ignited wildfire patterns and responses to policy shifts

    Science.gov (United States)

    M. L. Chas-Amil; J. P. Prestemon; C. J. McClean; J. Touza

    2015-01-01

    Development of efficient forest wildfire policies requires an understanding of the underlying reasons behind forest fire occurrences. Globally, there is a close relationship between forest wildfires and human activities; most wildfires are human events due to negligence (e.g., agricultural burning escapes) and deliberate actions (e.g., vandalism, pyromania, revenge,...

  2. Assessing the response of runoff to climate change and human ...

    Indian Academy of Sciences (India)

    34

    Hydrological cycle and water resources are commonly influenced by climate change and human activities (Vorosmarty et al., 2000; Beven, 2001; Kezer and Matsuyama, 2006;. IPCC, 2007; Zhang et al., 2007). Human activities such as Land Use/Cover Change. (LUCC), alters vegetation retention, soil water infiltration, and ...

  3. Modulation of human immune responses by bovine interleukin-10

    NARCIS (Netherlands)

    Hartog, den C.G.; Savelkoul, H.F.J.; Schoemaker, R.; Tijhaar, E.; Westphal, A.H.; Ruiter, de T.; Weg-Schrijver, van de Elise; Neerven, van R.J.J.

    2011-01-01

    Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood

  4. Worms under stress: C. elegans stress response and its relevance to complex human disease and aging

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.; Snoek, L.B.; Bono, de M.; Kammenga, J.E.

    2013-01-01

    Many organisms have stress response pathways, components of which share homology with players in complex human disease pathways. Research on stress response in the nematode worm Caenorhabditis elegans has provided detailed insights into the genetic and molecular mechanisms underlying complex human

  5. Human and rabbit eye responses to chemical insult.

    Science.gov (United States)

    Freeberg, F E; Nixon, G A; Reer, P J; Weaver, J E; Bruce, R D; Griffith, J F; Sanders, L W

    1986-11-01

    Groups of eight human volunteers and eight albino rabbits, under controlled laboratory conditions, were exposed in one eye without subsequent rinsing to the same concentrations and volumes of four prototype consumer products: fabric softener, shampoo, hand soap, and laundry detergent. Dose volume was 0.10 or 0.01 ml. The dose concentrations were selected to produce moderate effects with recovery within 24 to 48 hr. Two irritation scales were employed with both human and animal subjects: the Draize scale by a technician and a medical scale used with slit lamp examination by an ophthalmologist. Eyes were examined by both graders before and after dosing at specified intervals until recovery. Mean and maximum irritation scores are presented for each grading time, method, and exposure, as are the mean hours to recovery (clearing) for each exposure. Recovery times for human eyes were consistent with those reported previously for accidental human exposures to similar materials. Correlation coefficients for time to clear, comparing human vs rabbit for each dose volume-species combination across the four test products, were 0.72, 0.1 ml-human vs 0.01 ml-rabbit; 0.66, 0.01 ml-human vs 0.01 ml-rabbit; 0.40, 0.01 ml-human vs 0.1 ml-rabbit; 0.35, 0.1 ml-human vs 0.1 ml-rabbit. Thus, recovery time obtained under conditions of the "Low-Volume" test (0.01 ml-rabbit) better correlates with human eye recovery time (either dose volume) than does recovery time under Draize test conditions (0.10 ml-rabbit).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Single sodium channels from human skeletal muscle in planar lipid bilayers: characterization and response to pentobarbital

    NARCIS (Netherlands)

    Wartenberg, Hans C.; Urban, Bernd W.

    2004-01-01

    PURPOSE: To investigate the response to general anesthetics of different sodium-channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human skeletal muscle and compared them to existing data from human brain and human ventricular

  7. Modeling the Effect of Olivocochlear Efferents on the Subcortical Envelope Following Response in Humans

    Science.gov (United States)

    2016-11-28

    Title: Modeling the Effect of Olivocochlear Efferents on the Subcortical Envelope Following Response in Humans Christopher J. Smalt*, Michael G...added some of the dynamic characteristics of the MOCR with the more recent “ humanized ” version (Zilany, et al., 2014). This effect of the model is to...effectively reduce the outer hair cell gain, depending on the stimulus frequency, level, and timing. Human Envelope Following Responses (EFRs

  8. Gallbladder emptying response to sham feeding in humans

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, R.S.; Rock, E.; Malmud, L.S.

    1986-06-01

    Cholescintigraphy, using 99mTc-HIDA, was employed to determine the gallbladder emptying response to sham feeding of a steak and potato meal, and to compare it with the emptying responses to direct cholinergic stimulation by bethanechol and to ingestion of the test meal. The maximal cumulative gallbladder emptying response to sham feeding was 44.1% + 10.1%, which was not significantly different from the response to bethanechol. Cholinergic blockade with atropine eliminated the emptying response to sham feeding. Also, sham feeding did not stimulate gallbladder emptying in patients with vagotomy. This study suggests that intact vagus nerves and cholinergic pathways are required in order for the gallbladder to respond to sham feeding. The precise mechanism for this effect has not been elucidated.

  9. Innate Immune Responses to TLR2 and TLR4 Agonists Differ between Baboons, Chimpanzees and Humans

    Science.gov (United States)

    Brinkworth, Jessica F.; Pechenkina, Ekaterina A.; Silver, Jack; Goyert, Sanna M.

    2012-01-01

    Background African catarrhine primates differ in bacterial disease susceptibility. Methods Human, chimpanzee, and baboon blood was stimulated with TLR-detected bacterial agonists and cytokine/chemokine induction assessed by real-time pcr. Results Humans and chimpanzees shared similar cytokine/chemokine responses, while baboon cytokine/chemokine induction differed. Generally, responses were agonist-independent. Conclusions These primates tend to generate species rather than agonist–specific responses to bacterial agonists. PMID:22978822

  10. Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It: Incorporating Human Rights into the Sustainability Agenda

    Science.gov (United States)

    McPhail, Ken

    2013-01-01

    The Preamble to the Universal Declaration on Human Rights (UNDHR) calls on every organ of society to teach and educate for the promotion of the rights it contains. However, few if any business schools have any systematic or critical human rights content in their accounting and business curricula. This oversight is increasingly problematic as…

  11. Human Bronchial Epithelial Cell Response to Heavy Particle Exposure

    Science.gov (United States)

    Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Peyton, Michael; Larsen, Jill

    2012-07-01

    A battery of non-oncogenically immortalized human bronchial epithelial cells (HBECs) are being used to examine the molecular changes that lead to lung carcinogenesis after exposure to heavy particles found in the free space environment. The goal is to ultimately identify biomarkers of radioresponse that can be used for prediction of carcinogenic risk for fatal lung cancer. Our initial studies have focused on the cell line HBEC3 KT and the isogenic variant HBEC3 KTR53, which overexpresses the RASv12 mutant and where p53 has been knocked down by shRNA, and is considered to be a more oncogenically progressed variant. We have previously described the response of HBEC3 KT at the cellular and molecular level, however, the focus here is on the rate of cellular transformation after HZE radiation exposure and the molecular changes in transformed cells. When comparing the two cell lines we find that there is a maximum rate of cellular transformation at 0.25 Gy when cells are exposed to 1 GeV Fe particles, and, for the HBEC3 KTR53 there are multiple pathways upregulated that promote anchorage independent growth including the mTOR pathway, the TGF-1 pathway, RhoA signaling and the ERK/MAPK pathway as early as 2 weeks after radiation. This does not occur in the HBEC3 KT cell line. Transformed HBEC3 KT cells do not show any morphologic or phenotypic changes when grown as cell cultures. HBEC3 KTR53 cells on the other hand show substantial changes in morphology from a cobblestone epithelial appearance to a mesenchymal appearance with a lack of contact inhibition. This epithelial to mesenchymal change in morphology is accompanied by the expression of vimentin and a reduction in the expression of E-cadherin, which are hallmarks of epithelial to mesenchymal transition. Interestingly, for HBEC3 KT transformed cells there are no mutations in the p53 gene, 2 of 15 clones were found to be heterozygous for the RASV12 mutation, and 3 of 15 clones expressed high levels of BigH3, a TGFB-responsive

  12. Genetic Factors Modulating the Response to Stimulant Drugs in Humans

    OpenAIRE

    Hart, Amy B.; de Wit, Harriet; Palmer, Abraham A.

    2012-01-01

    Individuals vary in their responses to stimulant drugs, and several lines of evidence suggest that the basis for this variation is at least partially genetic in origin. Association studies have examined the effects of polymorphisms in specific genes on acute and chronic responses to stimulant drugs. Several of these genetic polymorphisms are also associated with other psychiatric dimensions and disorders. This chapter examines the evidence for genetic associations between the genes that have ...

  13. Effect of clothing material on thermal responses of the human body

    Science.gov (United States)

    Fengzhi, Li; Yi, Li

    2005-09-01

    The influence of clothing material on thermal responses of the human body are investigated by using an integrated model of a clothed thermoregulatory human body. A modified 25-nodes model considering the sweat accumulation on the skin surface is applied to simulate the human physiological regulatory responses. The heat and moisture coupled transfer mechanisms, including water vapour diffusion, the moisture evaporation/condensation, the moisture sorbtion/desorption by fibres, liquid sweat transfer under capillary pressure, and latent heat absorption/release due to phase change, are considered in the clothing model. On comparing prediction results with the experimental data in the literature, the proposed model seems able to predict dynamic heat and moisture transfer between the human body and the clothing system. The human body's thermal responses and clothing temperature and moisture variations are compared for different clothing materials during transient periods. We concluded that the hygroscopicity of clothing materials influences the human thermoregulation process significantly during environmental transients.

  14. Baroreflex Responses to Acute Changes in Blood Volume in Humans

    Science.gov (United States)

    Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

    1990-01-01

    To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro-reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationship, of the cardio-pulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venous Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). The results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

  15. The evolution of predictive adaptive responses in human life history

    NARCIS (Netherlands)

    Nettle, D.; Frankenhuis, W.E.; Rickard, I.J.

    2012-01-01

    Many studies in humans have shown that adverse experience in early life is associated with accelerated reproductive timing, and there is comparative evidence for similar effects in other animals. There are two different classes of adaptive explanation for associations between early-life adversity

  16. Hearing the Cries of the Poor: Healthcare as Human Response

    Science.gov (United States)

    Robinson, Adam M., Jr.

    2010-01-01

    The keynote address of Vice Admiral Adam Robinson, Surgeon General of the United States Navy, summarizes the integration of healthcare humanitarian assistance as central to the Navy's mission of defending and promoting world peace. Citing various examples of current programs and initiatives, the address explores the critical place of human hope as…

  17. Balance responses to lateral perturbations in human treadmill walking

    NARCIS (Netherlands)

    Hof, A. L.; Vermerris, S. M.; Gjaltema, W. A.

    2010-01-01

    During walking on a treadmill 10 human subjects (mean age 20 years) were perturbed by 100 ms pushes or pulls to the left or the right, of various magnitudes and in various phases of the gait cycle. Balance was maintained by (1) a stepping strategy (synergy), in which the foot at the next step is

  18. Equivalent refractive index of the human lens upon accommodative response

    NARCIS (Netherlands)

    Hermans, E.A.; Dubbelman, M.; van der Heijde, R.G.L.; Heethaar, R.M.

    2008-01-01

    PURPOSE.: To experimentally verify the suggestion of Gullstrand (1909), i.e., that the equivalent refractive index of the human lens increases with accommodation. METHODS.: The left eye of five subjects was focused on different accommodation stimuli, while the right eye was imaged with Scheimpflug

  19. Normal RNAi response in human fragile x fibroblasts

    DEFF Research Database (Denmark)

    Madsen, Charlotte; Grønskov, Karen; Brøndum-Nielsen, Karen

    2009-01-01

    BACKGROUND: Fragile x syndrome is caused by loss of expression of the FMRP protein involved in the control of a large number of mRNA targets. The Drosophila ortholog dFXR interacts with a protein complex that includes Argonaute2, an essential component of the RNA-induced silencing complex (RISC......). Furthermore dFXR associates with Dicer, another essential processing enzyme of the RNAi pathway. Both microRNA and microRNA precursors can co-immunoprecipitate with dFXR. Consequently it has been suggested that the Fragile x syndrome may be due to a defect in an RNAi-related apparatus. FINDINGS: We have...... investigated the RNAi response in Fragile x patient cells lacking FMRP compared with normal controls. RNAi responses were successfully detected, but no statistically significant difference between the response in normal cells compared to patients cells was found - neither one nor two days after transfection...

  20. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  1. Human antibody response to Lethocerus salivary antigens as a ...

    African Journals Online (AJOL)

    Interestingly in addition to a few immunogenic salivary proteins (85, 64, 37 and 33 kDa bands), a 28 kDa protein derived from salivary glands homogenate of aquatic insects was able to bind to Mycobacterium ulcerans and to be recognized by IgG antibodies of healthy subjects in endemic areas. The antibody responses to ...

  2. Cerebrovascular response to acute metabolic acidosis in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  3. Physiological responses to exposure to carbon dioxide and human bioeffluents

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2015-01-01

    Present paper describes physiological responses as a result of exposures to CO2 (between 500 ppm to 3,000 ppm) with and without bioeffluents. Twenty-five subjects participated. They were exposed in the climate chamber for 255 minutes in groups of five at a time. During exposure, they performed...

  4. Investigating Human Dendritic Cell Immune Responses to Borrelia burgdorferi

    NARCIS (Netherlands)

    Mason, Lauren M. K.; Hovius, Joppe W. R.

    2018-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells that recognize and phagocytose pathogens, and help to orchestrate adaptive immune responses to combat them. DCs are abundant in the skin where Borrelia burgdorferi first enters the body during a tick bite, and are thus critical in

  5. Extinction of aversive classically conditioned human sexual response

    NARCIS (Netherlands)

    Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Both, Stephanie

    2015-01-01

    Research has shown that acquired subjective likes and dislikes are quite resistant to extinction. Moreover, studies on female sexual response demonstrated that diminished genital arousal and positive affect toward erotic stimuli due to aversive classical conditioning did not extinguish during an

  6. Human cortical traveling waves: dynamical properties and correlations with responses.

    Directory of Open Access Journals (Sweden)

    Timothy M Patten

    Full Text Available The spatiotemporal behavior of human EEG oscillations is investigated. Traveling waves in the alpha and theta ranges are found to be common in both prestimulus and poststimulus EEG activity. The dynamical properties of these waves, including their speeds, directions, and durations, are systematically characterized for the first time, and the results show that there are significant changes of prestimulus spontaneous waves in the presence of an external stimulus. Furthermore, the functional relevance of these waves is examined by studying how they are correlated with reaction times on a single trial basis; prestimulus alpha waves traveling in the frontal-to-occipital direction are found to be most correlated to reaction speeds. These findings suggest that propagating waves of brain oscillations might be involved in mediating long-range interactions between widely distributed parts of human cortex.

  7. Measuring Human Performance within Computer Security Incident Response Teams

    Energy Technology Data Exchange (ETDEWEB)

    McClain, Jonathan T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Silva, Austin Ray [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Avina, Glory Emmanuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Forsythe, James C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-09-01

    Human performance has become a pertinen t issue within cyber security. However, this research has been stymied by the limited availability of expert cyber security professionals. This is partly attributable to the ongoing workload faced by cyber security professionals, which is compound ed by the limited number of qualified personnel and turnover of p ersonnel across organizations. Additionally, it is difficult to conduct research, and particularly, openly published research, due to the sensitivity inherent to cyber ope rations at most orga nizations. As an alternative, the current research has focused on data collection during cyb er security training exercises. These events draw individuals with a range of knowledge and experience extending from seasoned professionals to recent college gradu ates to college students. The current paper describes research involving data collection at two separate cyber security exercises. This data collection involved multiple measures which included behavioral performance based on human - machine transactions and questionnaire - based assessments of cyber security experience.

  8. Human Abuses of Coral Reefs- Adaptive Responses and Regime Transitions

    OpenAIRE

    Nordemar, Ingrid

    2004-01-01

    During the last few decades, coral reefs have become a disappearing feature of tropical marine environments, and those reefs that do remain are severely threatened. It is understood that humans have greately altered the environment under which these ecosystems previously have thrived and evoloved. Overharvesting of fish stocks, global warming and pollution are some of the most prominent threats, acting on coral reefs at several spatial and temporal scales. Presently, it is common that coral r...

  9. Human visual cortical responses to specular and matte motion flows

    Directory of Open Access Journals (Sweden)

    Tae-Eui eKam

    2015-10-01

    Full Text Available Determining the compositional properties of surfaces in the environment is an important visual capacity. One such property is specular reflectance, which encompasses the range from matte to shiny surfaces. Visual estimation of specular reflectance can be informed by characteristic motion profiles; a surface with a specular reflectance that is difficult to determine while static can be confidently disambiguated when set in motion. Here, we used fMRI to trace the sensitivity of human visual cortex to such motion cues, both with and without photometric cues to specular reflectance. Participants viewed rotating blob-like objects that were rendered as images (photometric or dots (kinematic with either matte-consistent or shiny-consistent specular reflectance profiles. We were unable to identify any areas in low and mid-level human visual cortex that responded preferentially to surface specular reflectance from motion. However, univariate and multivariate analyses identified several visual areas; V1, V2, V3, V3A/B, and hMT+, capable of differentiating shiny from matte surface flows. These results indicate that the machinery for extracting kinematic cues is present in human visual cortex, but the areas involved in integrating such information with the photometric cues necessary for surface specular reflectance remain unclear.

  10. Human-lamb bonding: oxytocin, cortisol and behavioural responses of lambs to human contacts and social separation.

    Science.gov (United States)

    Coulon, Marjorie; Nowak, Raymond; Andanson, Stéphane; Ravel, Christine; Marnet, Pierre Guy; Boissy, Alain; Boivin, Xavier

    2013-04-01

    Friendly interactions between humans and animals such as gentling or petting have been shown to have positive behavioural and physiological consequences in many species. In primates, rodents and dogs, oxytocin has been associated with tactile contact and anti-stress effects that may influence bonding and responses to stress situations. However the activation of the oxytocinergic system in other human-animal interactions such as with herbivores, had not yet been studied. Sixteen female lambs were reared by artificial feeding reinforced with 3× 30 s daily stroking sessions. At 6 weeks of age, the test consisted in measuring first plasma oxytocin and cortisol responses in lambs during a first 6-min phase in the home pen where the familiar caregiver gently stroked the lamb, and then physiological and behavioural responses in a test pen during a 20-min - phase of social isolation followed by a 20-min - phase of reunion with its familiar caregiver. The lambs expressed behavioural agitation during the whole period of isolation. A strong affiliative response towards the human and a sustained reduction of the agitation behaviour were observed during reunion. Lambs' behaviours when isolated and when in contact with the human were correlated suggesting a response to social separation from the familiar caregiver more than to social isolation from congeners. No significant changes in cortisol levels were observed during the test. Oxytocin levels did not vary during human contact, but increased when the familiar caregiver left the lamb alone in the test pen. In conclusion, lambs displayed affiliative responses towards their caregiver, and the lack of cortisol response during isolation while oxytocin was released suggest an anti-stress effect of oxytocin. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  12. Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

    Directory of Open Access Journals (Sweden)

    Claudia Palena

    2010-01-01

    Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

  13. Neural Markers of Responsiveness to the Environment in Human Sleep

    DEFF Research Database (Denmark)

    Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai

    2016-01-01

    Sleep is characterized by a loss of behavioral responsiveness. However, recent research has shown that the sleeping brain is not completely disconnected from its environment. How neural activity constrains the ability to process sensory information while asleep is yet unclear. Here, we instructed...... by Lempel-Ziv complexity (LZc), a measure shown to track arousal in sleep and anesthesia. Neural activity related to the semantic content of stimuli was conserved in light non-rapid eye movement (NREM) sleep. However, these processes were suppressed in deep NREM sleep and, importantly, also in REM sleep......, despite the recovery of wake-like neural activity in the latter. In NREM sleep, sensory activations were counterbalanced by evoked down states, which, when present, blocked further processing of external information. In addition, responsiveness markers correlated positively with baseline complexity, which...

  14. Cytokines and dysregulation of the immune response in human malaria

    Directory of Open Access Journals (Sweden)

    M. Fátima C. Alves

    1992-01-01

    Full Text Available The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-I (IL-1 in malaria are lacking. We found that only 2 out of 35 subjectswith acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T- lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 ñ 2,900 and P. vivax malaria (13,000 ñ 3,300, as compared to that of healthy individuals (27,000 ñ 3,000. Addition of IL-1 partially reserved depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2.

  15. Profile of the Engineer of 2001: The Engineer's Full Human Responsibility.

    Science.gov (United States)

    Kihlman, Tor

    1988-01-01

    Discusses a change in engineering education emphasizing human responsibility for environment, natural resources and reactions concerning technology. Describes the Swedish education system and a change in the curricula at Chalmers University of Technology in Sweden. (Author/YP)

  16. Predicting a Human Gut Microbiota's Response to Diet in Gnotobiotic Mice

    National Research Council Canada - National Science Library

    Jeremiah J. Faith; Nathan P. McNulty; Federico E. Rey; Jeffrey I. Gordon

    2011-01-01

    .... A model community of 10 sequenced human gut bacteria was introduced into gnotobiotic mice, and changes in species abundance and microbial gene expression were measured in response to randomized...

  17. Modeling the Biodynamical Response of the Human Thorax With Body Armor From a Bullet Impact

    National Research Council Canada - National Science Library

    Lobuono, John

    2001-01-01

    The objective of this study is to develop a finite element model of the human thorax with a protective body armor system so that the model can adequately determine the thorax's biodynamical response...

  18. Modeling the Biodynamical Response of the Human Thorax with Body Armor from a Bullet Impact

    National Research Council Canada - National Science Library

    Lobuono, John

    2001-01-01

    The objective of this study is to develop a finite element model of the human thorax with a protective body armor system so that the model can adequately determine the thorax's biodynamical response...

  19. Designing, developing, and deploying systems to support human-robot teams in disaster response

    NARCIS (Netherlands)

    Kruijff, G.J.M.; Kruijff-Korbayová, I.; Keshavdas, S.; Larochelle, B.; Janíček, M.; Colas, F.; Liu, M.; Pomerleau, F.; Siegwart, R.; Neerincx, M.A.; Looije, R.; Smets, N.J.J.M.; Mioch, T.; Diggelen, J. van; Pirri, F.; Gianni, M.; Ferri, F.; Menna, M.; Worst, R.; Linder, T.; Tretyakov, V.; Surmann, H.; Svoboda, T.; Reinštein, M.; Zimmermann, K.; Petříček, T.; Hlaváč, V.

    2014-01-01

    This paper describes our experience in designing, developing and deploying systems for supporting human-robot teams during disaster response. It is based on R&D performed in the EU-funded project NIFTi. NIFTi aimed at building intelligent, collaborative robots that could work together with humans in

  20. Response to "The Shaky Legal Foundations of the Global Human Rights Education Project"

    Science.gov (United States)

    Tibbitts, Felisa

    2015-01-01

    This article is a response to "The Shaky Legal Foundations of the Global Human Rights Education Project," an article written by Barend Vlaardingerbroek, in which Vlaardingerbroek characterizes current practices of human rights education (HRE) as having an overriding agenda of activism, one that can draw on an ideologically-driven…

  1. Diverting attention suppresses human amygdala responses to faces

    Directory of Open Access Journals (Sweden)

    Carmen eMorawetz

    2010-12-01

    Full Text Available Recent neuroimaging studies disagree as to whether the processing of emotion-laden visual stimuli is dependent upon the availability of attentional resources or entirely capacity-free. Two main factors have been proposed to be responsible for the discrepancies: the differences in the perceptual attentional demands of the tasks used to divert attentional resources from emotional stimuli and the spatial location of the affective stimuli in the visual field. To date, no neuroimaging report addressed these two issues in the same set of subjects. Therefore, the aim of the study was to investigate the effects of high and low attentional load as well as different stimulus locations on face processing in the amygdala using fMRI to provide further evidence for one of the two opposing theories. We were able for the first time to directly test the interaction of attentional load and spatial location. The results revealed a strong attenuation of amygdala activity when the attentional load was high. The eccentricity of the emotional stimuli did not affect responses in the amygdala and no interaction effect between attentional load and spatial location was found. We conclude that the processing of emotional stimuli in the amygdala is strongly dependent on the availability of attentional resources without a preferred processing of stimuli presented in the periphery and provide firm evidence for the concept of the attentional load theory of emotional processing in the amygdala.

  2. Human temporal-lobe response to vocal sounds.

    Science.gov (United States)

    Belin, Pascal; Zatorre, Robert J; Ahad, Pierre

    2002-02-01

    Voice is not only the vehicle of speech, it is also an 'auditory face' that conveys a wealth of information on a person's identity and affective state. In contrast to speech perception, little is known about the neural bases of our ability to perceive these various types of paralinguistic vocal information. Using functional magnetic resonance imaging (fMRI), we identified regions along the superior temporal sulcus (STS) that were not only sensitive, but also highly selective to vocal sounds. In the present study, we asked how neural activity in the voice areas was influenced by (i) the presence or not of linguistic information in the vocal input (speech vs. nonspeech) and (ii) frequency scrambling. Speech sounds were found to elicit greater responses than nonspeech vocalizations in most parts of auditory cortex, including primary auditory cortex (A1), on both sides of the brain. In contrast, response attenuation due to frequency scrambling was much more pronounced in anterior STS areas than at the level of A1. Importantly, only right anterior STS regions responded more strongly to nonspeech vocal sounds than to their scrambled version, suggesting that these regions could be specifically involved in paralinguistic aspects of voice perception.

  3. Human response to ductless personalized ventilation coupled with displacement ventilation

    DEFF Research Database (Denmark)

    Dalewski, Mariusz; Veselý, Michal; Melikov, Arsen K.

    2012-01-01

    A human subject experiment was carried out to investigate the extent to which ductless personalized ventilation (DPV) in conjunction with displacement ventilation can improve perceived air quality (PAQ) and thermal comfort at elevated room air temperature in comparison with displacement ventilation...... alone. The experimental conditions comprised displacement ventilation alone (room air temperature of 23 °C, 26 °C, 29 °C) and DPV with displacement ventilation (26 °C, 29 °C), both operating at supply air temperatures 3, 5 or 6K lower than room air temperature, as well as mixing ventilation (23 °C, 3 K......). During one hour exposure participants answered questionnaires regarding PAQ and thermal comfort. PAQ was significantly better with DPV than without DPV at the same background conditions. Thermal comfort improved when DPV was used. Combining DPV with displacement ventilation showed the potential...

  4. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways

    NARCIS (Netherlands)

    Baarlen, van P.; Troost, F.J.; Meer, van der C.; Hooiveld, G.J.E.J.; Boekschoten, M.V.; Brummer, R.J.; Kleerebezem, M.

    2011-01-01

    Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function through largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy

  5. Methods of Assessing Human Tendon Metabolism and Tissue Properties in Response to Changes in Mechanical Loading

    DEFF Research Database (Denmark)

    Heinemeier, Katja M; Kjaer, Michael; Magnusson, S Peter

    2016-01-01

    In recent years a number of methodological developments have improved the opportunities to study human tendon. Microdialysis enables sampling of interstitial fluid in the peritendon tissue, while sampling of human tendon biopsies allows direct analysis of tendon tissue for gene- and protein......)), and tendon mechanical properties (ultrasonography combined with force measurement during movement). Finally, 3D cell cultures of human tendon cells provide the opportunity to investigate cell-matrix interactions in response to various interventions....

  6. Proceedings of the Second Workshop on Numerical Analysis of Human and Surrogate Response to Accelerative Loading

    Science.gov (United States)

    2018-02-01

    induced load transfer to porcine and human head ARL 15:15 Keegan Yates Identifying TBI Thresholds using Animal and Human FEM...25 Tusit Weerasooriya Mechanical Response of Human and Animal Bones: Overview of ARL Experimental Research ARL 11:50 Wayne Chen...Distribution A • One question was raised in the end discussion. Are we building these ATDs only with current vehicles in mind , will they be robust enough

  7. DMPD: Differential responses of human monocytes and macrophages to IL-4 and IL-13. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534111 Differential responses of human monocytes and macrophages to IL-4 and IL-1...):575-8. (.png) (.svg) (.html) (.csml) Show Differential responses of human monocytes and macrophages to IL-...4 and IL-13. PubmedID 10534111 Title Differential responses of human monocytes an

  8. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

    2009-10-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

  9. Bystander T cells in human immune responses to dengue antigens

    Directory of Open Access Journals (Sweden)

    Suwannasaen Duangchan

    2010-09-01

    Full Text Available Abstract Background Previous studies of T cell activation in dengue infection have focused on restriction of specific T cell receptors (TCRs and classical MHC molecules. However, bystander T cell activation, which is TCR independent, occurs via cytokines in other viral infections, both in vitro and in vivo, and enables T cells to bypass certain control checkpoints. Moreover, clinical and pathological evidence has pointed to cytokines as the mediators of dengue disease severity. Therefore, we investigated bystander T cell induction by dengue viral antigen. Results Whole blood samples from 55 Thai schoolchildren aged 13-14 years were assayed for in vitro interferon-gamma (IFN-γ induction in response to inactivated dengue serotype 2 antigen (Den2. The contribution of TCR-dependent and independent pathways was tested by treatment with cyclosporin A (CsA, which inhibits TCR-dependent activation of T cells. ELISA results revealed that approximately 72% of IFN-γ production occurred via the TCR-dependent pathway. The major IFN-γ sources were natural killer (NK (mean ± SE = 55.2 ± 3.3, CD4+T (24.5 ± 3.3 and CD8+T cells (17.9 ± 1.5, respectively, as demonstrated by four-color flow cytometry. Interestingly, in addition to these cells, we found CsA-resistant IFN-γ producing T cells (CD4+T = 26.9 ± 3.6% and CD8+T = 20.3 ± 2.1% implying the existence of activated bystander T cells in response to dengue antigen in vitro. These bystander CD4+ and CD8+T cells had similar kinetics to NK cells, appeared after 12 h and were inhibited by anti-IL-12 neutralization indicating cytokine involvement. Conclusions This study described immune cell profiles and highlighted bystander T cell activation in response to dengue viral antigens of healthy people in an endemic area. Further studies on bystander T cell activation in dengue viral infection may reveal the immune mechanisms that protect or enhance pathogenesis of secondary dengue infection.

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

    Science.gov (United States)

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

    2009-10-01

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

  11. Humanity and Social Responsibility, Solidarity, and Social Rights.

    Science.gov (United States)

    Ahola-Launonen, Johanna

    2016-04-01

    This article discusses the suggestion of having the notion of solidarity as the foundational value for welfare scheme reforms. Solidarity is an emerging concept in bioethical deliberations emphasizing the need for value-oriented discussion in revising healthcare structures, and the notion has been contrasted with liberal justice and rights. I suggest that this contrast is unnecessary, flawed, and potentially counterproductive. As necessary as the sense of solidarity is in a society, it is an insufficient concept to secure the goals related to social responsibility. The discussion on solidarity is also based on a questionable sense of nostalgia. Furthermore, solidarity and liberal justice share essential objectives concerning welfare schemes; therefore, the question arises whether the proper comparison should in the first place be within justice and solidarity.

  12. Human response to vibroacoustic environments of space vehicles

    Science.gov (United States)

    Willshire, K. F.

    1984-01-01

    To insure efficient utilization of the system, space station design and operations will require special habitability considerations for the occupants and crew because of the relatively long duration missions. Of particular concern is the environment in which the personnel will live and work, and how it affects both the performance and comfort of the occupants. Current criteria do not consider possible effects of reduced gravity, long duration, and confinement. Preliminary to developing space station vibroacoustic habitability criteria, the adequacy of criteria for other space vehicles has been reviewed. In this paper, responses to the noise and vibration environments of both Skylab and Shuttle are discussed. Some astronauts have reported sleep interference, communication interference, distraction, and general annoyance as noise related complaints. In addition, information from the Russian Salyut missions, as well as similar based situtations (e.g., submarines), is reviewed.

  13. Hallucinogenic drugs attenuate the subjective response to alcohol in humans.

    Science.gov (United States)

    Barrett, Sean P; Archambault, Jennifer; Engelberg, Marla J; Pihl, Robert O

    2000-10-01

    This study investigated possible interactions between alcohol and hallucinogens in 22 lysergic acid diethylamide (LSD) and/or psilocybin users through retrospective structured interviews. Of those who had used LSD with alcohol, 86;7 per cent reported a complete blockade of subjective alcohol effects, while the remaining cases reported a diminished response. In addition, 60 per cent of respondents who had used alcohol and psilocybin together reported a partial antagonism of subjective alcohol effects.T-test analyses revealed that LSD's antagonism of alcohol effects were significantly greater than those associated with psilocybin. It is proposed that LSD's effect on alcohol intoxication may involve interactions with various serotonergic and/or dopaminergic receptor systems. Copyright 2000 John Wiley & Sons, Ltd.

  14. Human responses to the 1906 eruption of Vesuvius, southern Italy

    Science.gov (United States)

    Chester, David; Duncan, Angus; Kilburn, Christopher; Sangster, Heather; Solana, Carmen

    2015-04-01

    Cultural and political contexts are important in determining the ways in which communities respond to volcanic eruptions. Understanding the manner in which communities and the State apparatus have coped with historic eruptions can provide insights into how responses have influenced vulnerability and resilience. The 1906 eruption of Vesuvius is well suited for such a study as it was one of the first major eruptions in which there was a significant element of State control, and this worked alongside more traditional pre-industrial responses. This eruption was extensively reported in the regional, national and international press and in archives which include still photography. One feature is the rich archive of material published in English language newspapers of record which are analysed fully in the paper for the first time. Many of these data sources are now accessible on-line. The eruption started on April 4th with mild explosive activity and the eruption of lava from 5th to 7th April. On the night of the 7th/8th, activity intensified when a vigorous lava fountain inclined obliquely to the north east, deposited a thick layer of tephra on the towns of Ottaviano and San Giuseppe. This led to roof collapse and a large number of fatalities. There was increased lava emission and a flow progressed south through the outskirts of Boscotrecase cutting the Circumvesuviana railway line and almost reaching Torre Annunziata. Following April 8th the eruption declined and ended on April 21st. In the initial responses to the eruption pre-industrial features were prominent, with the local communities showing social cohesion, self-reliance and little panic. A more negative aspect was the traditional religious response that involved the use of liturgies of divine appeasement and which included the use of saintly relics and images. There is interesting evidence, however, that this coping strategy was driven by the populace rather than by the clergy. The inhabitants of San Giuseppe

  15. Physiological responses to exposure to carbon dioxide and human bioeffluents

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2015-01-01

    Present paper describes physiological responses as a result of exposures to CO2 (between 500 ppm to 3,000 ppm) with and without bioeffluents. Twenty-five subjects participated. They were exposed in the climate chamber for 255 minutes in groups of five at a time. During exposure, they performed...... different cognitive tasks and assessed their comfort and acute health symptoms. Besides, the following were determined: heart rate, blood pressure, oxygen saturation of blood, respiration rate, minute ventilation rate, nasal peak flow, forced expiratory volume, and the end-tidal CO2 pressure (ETCO2). Saliva...... samples were collected to analyze stress biomarkers. During exposure to CO2 with and without bioeffluents at 3,000 ppm, ETCO2 and minute ventilation rate were higher, while nasal peak flow decreased. These exposures caused also the increased heart rate during typing sessions. During exposures to CO2...

  16. On human dendritic cell subsets harnessing cytotoxic T-cell responses

    NARCIS (Netherlands)

    de Groot, R.

    2015-01-01

    In this work we explore the function of different dendritic cell (DC)-derived molecules in the induction of CTL responses. In chapter two we compare the capacity of two major human skin DC subsets to induce CTL responses, and we study which T-cell differentiating molecules are critical. In chapter

  17. Response stability and variability induced in humans by different feedback contingenies

    NARCIS (Netherlands)

    Maes, J.H.R.

    2003-01-01

    In two experiments, the behavioral effects of different response-feedback contingencies were examined with a task requiring human subjects to repeatedly type three-key sequences on a computer keyboard. In Experiment 1, the subjects first received positive feedback for response variability, followed

  18. Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Ravn, P; Demissie, A; Eguale, T

    1999-01-01

    Human T cell responses to ESAT-6 and eight synthetic overlapping peptides were investigated in tuberculosis (TB) patients and control subjects from regions of high and low endemicity for TB. ESAT-6 was recognized by 65% of all tuberculin purified protein derivative-responsive TB patients, whereas...

  19. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation

    NARCIS (Netherlands)

    Spronk, D.B.; De Bruijn, E.R.; van Wel, J.H.; Ramaekers, J.G.; Verkes, R.J.

    2016-01-01

    Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of

  20. Human Adolescent Phase Response Curves to Bright White Light.

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2017-08-01

    Older adolescents are particularly vulnerable to circadian misalignment and sleep restriction, primarily due to early school start times. Light can shift the circadian system and could help attenuate circadian misalignment; however, a phase response curve (PRC) to determine the optimal time for receiving light and avoiding light is not available for adolescents. We constructed light PRCs for late pubertal to postpubertal adolescents aged 14 to 17 years. Participants completed 2 counterbalanced 5-day laboratory sessions after 8 or 9 days of scheduled sleep at home. Each session included phase assessments to measure the dim light melatonin onset (DLMO) before and after 3 days of free-running through an ultradian light-dark (wake-sleep) cycle (2 h dim [~20 lux] light, 2 h dark). In one session, intermittent bright white light (~5000 lux; four 20-min exposures) was alternated with 10 min of dim room light once per day for 3 consecutive days. The time of light varied among participants to cover the 24-h day. For each individual, the phase shift to bright light was corrected for the free-run derived from the other laboratory session with no bright light. One PRC showed phase shifts in response to light start time relative to the DLMO and another relative to home sleep. Phase delay shifts occurred around the hours corresponding to home bedtime. Phase advances occurred during the hours surrounding wake time and later in the afternoon. The transition from delays to advances occurred at the midpoint of home sleep. The adolescent PRCs presented here provide a valuable tool to time bright light in adolescents.

  1. Global changes in biogeochemical cycles in response to human activities

    Science.gov (United States)

    Moore, Berrien, III; Melillo, Jerry

    1994-01-01

    The main objective of our research was to characterize biogeochemical cycles at continental and global scales in both terrestrial and aquatic ecosystems. This characterization applied to both natural ecosystems and those disturbed by human activity. The primary elements of interest were carbon and nitrogen and the analysis sought to quantify standing stocks and dynamic cycling processes. The translocation of major nutrients from the terrestrial landscape to the atmosphere (via trace gases) and to fluvial systems (via leaching, erosional losses, and point source pollution) were of particular importance to this study. Our aim was to develop the first generation of Earth System Models. Our research was organized around the construction and testing of component biogeochemical models which treated terrestrial ecosystem processes, aquatic nutrient transport through drainage basins, and trace gas exchanges at the continental and global scale. A suite of three complementary models were defined within this construct. The models were organized to operate at a 1/2 degree latitude by longitude level of spatial resolution and to execute at a monthly time step. This discretization afforded us the opportunity to understand the dynamics of the biosphere down to subregional scales, while simultaneously placing these dynamics into a global context.

  2. Asian monsoon extremes and humanity's response over the past millennium

    Science.gov (United States)

    Buckley, B. M.; Lieberman, V. B.; Zottoli, B.

    2012-12-01

    The first decade of the 21st century has seen significant development in the production of paleo proxies for the Asian monsoon, exemplified by the Monsoon Asian Drought Atlas that was comprised of more than 300 tree ring chronologies. Noteworthy among them is the Vietnamese cypress tree-ring record which reveals that the two worst droughts of the past 7 centuries, each more than a decade in length, coincided with the demise of the Khmer civilization at Angkor in the early 15th century CE. The 18th century was nearly as tumultuous a period across Southeast Asia, where several polities fell against a backdrop of epic decadal-scale droughts. At this time all of the region's charter states saw rapid realignment in the face of drought, famine, disease and a raft of related and unrelated social issues. Several other droughts, some more extreme but of lesser duration, punctuate the past millennium, but appear to have had little societal impact. Historical documentation is being used not only to provide corroborative evidence of tree-ring reconstructed climate extremes, but to attempt to understand the dynamics of the coupled human-natural systems involved, and to define what kinds of thresholds need to be reached before societies respond. This paleo perspective can assist our analyses of the role of climate extremes in the collapse or disruption of regional societies, a subject of increasing concern given the uncertainties surrounding projections for future climate across the highly populated areas of Asia.

  3. Response of human rheumatoid arthritis osteoblasts and osteoclasts to adiponectin.

    Science.gov (United States)

    Krumbholz, Grit; Junker, Susann; Meier, Florian M P; Rickert, Markus; Steinmeyer, Jürgen; Rehart, Stefan; Lange, Uwe; Frommer, Klaus W; Schett, Georg; Müller-Ladner, Ulf; Neumann, Elena

    2017-01-01

    Adiponectin is an effector molecule in the pathophysiology of rheumatoid arthritis, e.g. by inducing cytokines and matrix degrading enzymes in synovial fibroblasts. There is growing evidence that adiponectin affects osteoblasts and osteoclasts although the contribution to the aberrant bone metabolism in rheumatoid arthritis is unclear. Therefore, the adiponectin effects on rheumatoid arthritis-derived osteoblasts and osteoclasts were evaluated. Adiponectin and its receptors were examined in bone tissue. Primary human osteoblasts and osteoclasts were stimulated with adiponectin and analysed using realtime polymerase chain-reaction and immunoassays. Effects on matrix-production by osteoblasts and differentiation and resorptive activity of osteoclasts were examined. Immunohistochemistry of rheumatoid arthritis bone tissue showed adiponectin expression in key cells of bone remodelling. Adiponectin altered gene expression and cytokine release in osteoblasts and increased IL-8 secretion by osteoclasts. Adiponectin inhibited osterix and induced osteoprotegerin mRNA in osteoblasts. In osteoclasts, MMP-9 and tartrate resistant acid phosphatase expression was increased. Accordingly, mineralisation capacity of osteoblasts decreased whereas resorptive activity of osteoclasts increased. The results confirm the proinflammatory potential of adiponectin and support the idea that adiponectin influences rheumatoid arthritis bone remodelling through alterations in osteoblast and osteoclast.

  4. THE ROLE OF HUMAN RESOURCES IN PROMOTING THE CORPORATE SOCIAL RESPONSABILITY

    OpenAIRE

    IOAN PASTOR; CAMELIA-OLIVIA ILIES

    2011-01-01

    In a global economy, organizations have the responsibility to demonstrate and promote corporate social responsibility. Long-term sustainability demands that organizations rethink their business goals and objectives from focusing on making a profit to corporate citizenship. Human resource managers play a critical role – that of leading and educating their companies regarding the importance of corporate social responsability while at the same time strategically implementing healthy management p...

  5. Opponent melanopsin and S-cone signals in the human pupillary light response

    OpenAIRE

    Spitschan, Manuel; Jain, Sandeep; Brainard, David H.; Aguirre, Geoffrey K.

    2014-01-01

    Our eyes sense bright light using cones (L, M, and S) and recently discovered melanopsin-containing ganglion cells. Both S cones and melanopsin respond to blueish (short-wavelength) light. How does melanopsin interact with the cones in visual function? We measured the response of the human pupil to isolated stimulation of the different photoreceptors. Our work reveals a curious, opponent response to blue light in the otherwise familiar pupillary light response. Increased stimulation of S cone...

  6. What is human in humans? Responses from biology, anthropology, and philosophy.

    Science.gov (United States)

    Bibeau, Gilles

    2011-08-01

    Genomics has brought biology, medicine, agriculture, psychology, anthropology, and even philosophy to a new threshold. In this new context, the question about "what is human in humans" may end up being answered by geneticists, specialists of technoscience, and owners of biotech companies. The author defends, in this article, the idea that humanity is at risk in our age of genetic engineering, biotechnologies, and market-geared genetic research; he also argues that the values at the very core of our postgenomic era bring to its peak the science-based ideology that has developed since the time of Galileo, Newton, Descartes, and Harvey; finally, it shows that the bioindustry has invented a new genomythology that goes against the scientific evidence produced by the research in human sciences in which life is interpreted as a language.

  7. Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning.

    Science.gov (United States)

    Maxwell, Sean L; Venter, Oscar; Jones, Kendall R; Watson, James E M

    2015-10-01

    The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation. © 2015 New York Academy of Sciences.

  8. Electromyographic responses to imposed sinusoidal movement of the human thumb.

    Science.gov (United States)

    Brown, T I; Rack, P M; Ross, H F

    1982-11-01

    1. The interphalangeal joint of the thumb was driven through sinusoidal flexion-extension movements while electromyograms were recorded from over the flexor pollicis longus muscle. 2. When the subject relaxed his thumb the movement generated no detectable e.m.g. response. When, however, he exerted a voluntary flexing force electrical activity could be recorded from the flexor pollicis longus, the amplitude of which was modulated at the frequency of the movement. 3. As the driving frequency was increased, the maximal e.m.g. activity occurred progressively later in the cycle of movement; for frequencies above about 6 Hz the timing of the averaged e.m.g. was compatible with a reflex delay of 55-65 msec. 4. The frequency-phase plot was not, however, the perfect straight line that would arise from a simple and constant reflex delay. There were some consistent departures from linearity and some random variations. In either case, the timing of the e.m.g. and the timing of the reflex force (Brown, Rack & Ross, 1982a) changed together in ways that increased confidence in each of the measurements. 5. The amplitude of the e.m.g. signal was more deeply modulated by movements at 8-14 Hz than by higher or lower frequencies, and it was concluded that the stretch reflex responds particularly readily to signals in that frequency range.

  9. Human sensory response to acetone/air mixtures.

    Science.gov (United States)

    Salthammer, T; Schulz, N; Stolte, R; Uhde, E

    2016-10-01

    The release of organic compounds from building products may influence the perceived air quality in the indoor environment. Consequently, building products are assessed for chemical emissions and for the acceptability of emitted odors. A procedure for odor evaluations in test chambers is described by the standard ISO 16000-28. A panel of eight or more trained subjects directly determines the perceived intensity Π (unit pi) of an air sample via diffusers. For the training of the panelists, a comparative Π-scale is applied. The panelists can use acetone/air mixtures in a concentration range between 20 mg/m(3) (0 pi) and 320 mg/m(3) (15 pi) as reference. However, the training and calibration procedure itself can substantially contribute to the method uncertainty. This concerns the assumed odor threshold of acetone, the variability of panelist responses, and the analytical determination of acetone concentrations in air with online methods as well as the influence of the diffuser geometry and the airflow profile. © 2015 The Authors. Indoor Air published by John Wiley & Sons Ltd.

  10. Bridging the species divide: transgenic mice humanized for type-I interferon response.

    Directory of Open Access Journals (Sweden)

    Daniel Harari

    Full Text Available We have generated transgenic mice that harbor humanized type I interferon receptors (IFNARs enabling the study of type I human interferons (Hu-IFN-Is in mice. These "HyBNAR" (Hybrid IFNAR mice encode transgenic variants of IFNAR1 and IFNAR2 with the human extracellular domains being fused to transmembrane and cytoplasmic segments of mouse sequence. B16F1 mouse melanoma cells harboring the HyBNAR construct specifically bound Hu-IFN-Is and were rendered sensitive to Hu-IFN-I stimulated anti-proliferation, STAT1 activation and activation of a prototypical IFN-I response gene (MX2. HyBNAR mice were crossed with a transgenic strain expressing the luciferase reporter gene under the control of the IFN-responsive MX2 promoter (MX2-Luciferase. Both the HyBNAR and HyBNAR/MX2-Luciferase mice were responsive to all Hu-IFN-Is tested, inclusive of IFNα2A, IFNβ, and a human superagonist termed YNSα8. The mice displayed dose-dependent pharmacodynamic responses to Hu-IFN-I injection, as assessed by measuring the expression of IFN-responsive genes. Our studies also demonstrated a weak activation of endogenous mouse interferon response, especially after high dose administration of Hu-IFNs. In sharp contrast to data published for humans, our pharmacodynamic readouts demonstrate a very short-lived IFN-I response in mice, which is not enhanced by sub-cutaneous (SC injections in comparison to other administration routes. With algometric differences between humans and mice taken into account, the HyBNAR mice provides a convenient non-primate pre-clinical model to advance the study of human IFN-Is.

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

    Science.gov (United States)

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

    2010-07-21

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

  12. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    Science.gov (United States)

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  13. Fractional Diffusion Based Modelling and Prediction of Human Brain Response to External Stimuli

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2015-01-01

    Full Text Available Human brain response is the result of the overall ability of the brain in analyzing different internal and external stimuli and thus making the proper decisions. During the last decades scientists have discovered more about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research, there were fewer efforts which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling and prediction of the human EEG signal, as an alert state of overall human brain activity monitoring, upon receiving external stimuli, based on fractional diffusion equations. The results of this modeling show very good agreement with the real human EEG signal and thus this model can be used for many types of applications such as prediction of seizure onset in patient with epilepsy.

  14. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity.

    Science.gov (United States)

    Cole, Steven W; Levine, Morgan E; Arevalo, Jesusa M G; Ma, Jeffrey; Weir, David R; Crimmins, Eileen M

    2015-12-01

    Chronic social adversity activates a conserved transcriptional response to adversity (CTRA) marked by increased expression of pro-inflammatory genes and decreased expression of antiviral- and antibody-related genes. Recent findings suggest that some psychological resilience factors may help buffer CTRA activation, but the relative impact of resilience and adversity factors remains poorly understood. Here we examined the relative strength of CTRA association for the two best-established psychological correlates of CTRA gene expression-the risk factor of perceived social isolation (loneliness) and the resilience factor of eudaimonic well-being (purpose and meaning in life). Peripheral blood samples and validated measures of loneliness and eudaimonic well-being were analyzed in 108 community-dwelling older adults participating in the longitudinal US Health and Retirement Study (56% female, mean age 73). Mixed effect linear model analyses quantified the strength of association between CTRA gene expression and measures of loneliness and eudaimonic well-being in separate and joint analyses. As in previous studies, separate analyses found CTRA gene expression to be up-regulated in association with loneliness and down-regulated in association with eudaimonic well-being. In joint analyses, effects of loneliness were completely abrogated whereas eudaimonic well-being continued to associate with CTRA down-regulation. Similar eudaimonia-dominant effects were observed for positive and negative affect, optimism and pessimism, and anxiety symptoms. All results were independent of demographic and behavioral health risk factors. Eudaimonic well-being may have the potential to compensate for the adverse impact of loneliness on CTRA gene expression. Findings suggest a novel approach to targeting the health risks associated with social isolation by promoting purpose and meaning in life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Human in situ cytokine and leukocyte responses to acute smoking.

    Science.gov (United States)

    Kastelein, Tegan; Duffield, Rob; Marino, Frank

    2017-12-01

    This study examined immune/inflammatory parameters following an acute tobacco smoking episode in smokers with varying smoking histories. Twenty-eight male habitual smokers were categorized according to smoking history, e.g. younger smoker (YSM) or middle-aged smoker (MSM). Participants were matched for fitness and smoking habits and following baseline testing, undertook a smoking protocol involving consumption of two cigarettes within 15 min. Venous blood was collected pre- and immediately, 1 h, and 4 h post-protocol to permit analyses of circulating levels of interleukin (IL)-6, IL-1β, IL-1ra, monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP), and leukocytes. No baseline differences were observed between groups for IL-1ra, IL-1β, or leukocytes. MCP-1 and IL-6 levels were significantly (p < 0.05) elevated at baseline in YSM. Both groups showed an increase in MCP-1 levels from pre- to immediately post-cigarette consumption. The MSM also displayed an increase in IL-6 post-smoking, followed by a decline over the period from 1 to 4 h thereafter. A significant decline in circulating lymphocyte and eosinophil levels from immediately post-cigarette consumption to 1 h later was observed in both groups. Monocyte levels in the YSM followed a similar profile but no significant effects on this cell type were evident in the MSM. From these results, a 10-year difference in smoking history induces mild leukopenia. Altered responses due to smoking were also evident with respect to levels of circulating biomarkers, which may be indicative of an effect of differences in cumulative smoking history.

  16. Human cardiovascular dose-response to supplemental oxygen.

    Science.gov (United States)

    Bak, Z; Sjöberg, F; Rousseau, A; Steinvall, I; Janerot-Sjoberg, B

    2007-09-01

    The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree. Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23-48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol. Left ventricular stroke volume [86 +/- 13 to 75 +/- 9 mL (mean +/- SD)] and end-diastolic area (19.3 +/- 4.4 to 16.8 +/- 4.3 cm(2)) declined (P arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change. There is a linear dose-response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.

  17. Dynamic Edematous Response of the Human Heart to Myocardial Infarction

    Science.gov (United States)

    Fernández-Jiménez, Rodrigo; Barreiro-Pérez, Manuel; Martin-García, Ana; Sánchez-González, Javier; Agüero, Jaume; Galán-Arriola, Carlos; García-Prieto, Jaime; Díaz-Pelaez, Elena; Vara, Pedro; Martinez, Irene; Zamarro, Ivan; Garde, Beatriz; Sanz, Javier; Fuster, Valentin

    2017-01-01

    Background: Clinical protocols aimed to characterize the post–myocardial infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized to take account of dynamic biological phenomena evolving early after the index ischemic event. Here, we evaluated the time course of edema reaction in patients with ST-segment–elevation MI by CMR and assessed its implications for myocardium-at-risk (MaR) quantification both in patients and in a large-animal model. Methods: A total of 16 patients with anterior ST-segment–elevation MI successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR examinations were performed: patients with ST-segment–elevation MI were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were evaluated at all time points. In the experimental study, 20 pigs underwent 40-minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography during the index coronary occlusion. Generalized linear mixed models were used to take account of repeated measurements. Results: In humans, T2 relaxation time in the ischemic myocardium declines significantly from early after reperfusion to 24 hours, and then increases up to day 4, reaching a plateau from which it decreases from day 7. Consequently, edema extent measured by T2-weighted short-tau triple inversion-recovery (CMR-MaR) varied with the timing of the CMR examination. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were similar to values measured by reference contrast

  18. Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.

    Science.gov (United States)

    Hartmann, Boris M; Thakar, Juilee; Albrecht, Randy A; Avey, Stefan; Zaslavsky, Elena; Marjanovic, Nada; Chikina, Maria; Fribourg, Miguel; Hayot, Fernand; Schmolke, Mirco; Meng, Hailong; Wetmur, James; García-Sastre, Adolfo; Kleinstein, Steven H; Sealfon, Stuart C

    2015-10-01

    Influenza viruses continue to present global threats to human health. Antigenic drift and shift, genetic reassortment, and cross-species transmission generate new strains with differences in epidemiology and clinical severity. We compared the temporal transcriptional responses of human dendritic cells (DC) to infection with two pandemic (A/Brevig Mission/1/1918, A/California/4/2009) and two seasonal (A/New Caledonia/20/1999, A/Texas/36/1991) H1N1 influenza viruses. Strain-specific response differences included stronger activation of NF-κB following infection with A/New Caledonia/20/1999 and a unique cluster of genes expressed following infection with A/Brevig Mission/1/1918. A common antiviral program showing strain-specific timing was identified in the early DC response and found to correspond with reported transcript changes in blood during symptomatic human influenza virus infection. Comparison of the global responses to the seasonal and pandemic strains showed that a dramatic divergence occurred after 4 h, with only the seasonal strains inducing widespread mRNA loss. Continuously evolving influenza viruses present a global threat to human health; however, these host responses display strain-dependent differences that are incompletely understood. Thus, we conducted a detailed comparative study assessing the immune responses of human DC to infection with two pandemic and two seasonal H1N1 influenza strains. We identified in the immune response to viral infection both common and strain-specific features. Among the stain-specific elements were a time shift of the interferon-stimulated gene response, selective induction of NF-κB signaling by one of the seasonal strains, and massive RNA degradation as early as 4 h postinfection by the seasonal, but not the pandemic, viruses. These findings illuminate new aspects of the distinct differences in the immune responses to pandemic and seasonal influenza viruses. Copyright © 2015, American Society for Microbiology. All

  19. Response of human chondrocytes and mesenchymal stromal cells to a decellularized human dermis

    Directory of Open Access Journals (Sweden)

    Giavaresi Gianluca

    2013-01-01

    Full Text Available Abstract Background Although progress has been made in the treatment of articular cartilage lesions, they are still a major challenge because current techniques do not provide satisfactory long-term outcomes. Tissue engineering and the use of functional biomaterials might be an alternative regenerative strategy and fulfill clinical needs. Decellularized extracellular matrices have generated interest as functional biologic scaffolds, but there are few studies on cartilage regeneration. The aim of this study was to evaluate in vitro the biological influence of a newly developed decellularized human dermal extracellular matrix on two human primary cultures. Methods Normal human articular chondrocytes (NHAC-kn and human mesenchymal stromal cells (hMSC from healthy donors were seeded in polystyrene wells as controls (CTR, and on decellularized human dermis batches (HDM_derm for 7 and 14 days. Cellular proliferation and differentiation, and anabolic and catabolic synthetic activity were quantified at each experimental time. Histology and scanning electron microscopy were used to evaluate morphology and ultrastructure. Results Both cell cultures had a similar proliferation rate that increased significantly (p p p p p p p p Conclusions The results obtained showed that in in vitro conditions HDM_derm behaves as a suitable scaffold for the growth of both well-differentiated chondrocytes and undifferentiated mesenchymal cells, thus ensuring a biocompatible and bioactive substrate. Further studies are mandatory to test the use of HDM_derm with tissue engineering to assess its therapeutic and functional effectiveness in cartilage regeneration.

  20. Noninvasive Imaging of Human Immune Responses in a Human Xenograft Model of Graft-Versus-Host Disease.

    Science.gov (United States)

    Van Elssen, Catharina H M J; Rashidian, Mohammad; Vrbanac, Vladimir; Wucherpfennig, Kai W; Habre, Zeina El; Sticht, Jana; Freund, Christian; Jacobsen, Johanne T; Cragnolini, Juanjo; Ingram, Jessica; Plaisier, Loes; Spierings, Eric; Tager, Andrew M; Ploegh, Hidde L

    2017-06-01

    The immune system plays a crucial role in many diseases. Activation or suppression of immunity is often related to clinical outcome. Methods to explore the dynamics of immune responses are important to elucidate their role in conditions characterized by inflammation, such as infectious disease, cancer, or autoimmunity. Immuno-PET is a noninvasive method by which disease and immune cell infiltration can be explored simultaneously. Using radiolabeled antibodies or fragments derived from them, it is possible to image disease-specific antigens and immune cell subsets. Methods: We developed a method to noninvasively image human immune responses in a relevant humanized mouse model. We generated a camelid-derived single-domain antibody specific for human class II major histocompatibility complex products and used it to noninvasively image human immune cell reconstitution in nonobese diabetic severe combined immune deficiency γ-/- mice reconstituted with human fetal thymus, liver, and liver-derived hematopoietic stem cells (BLT mice). Results: We showed imaging of infiltrating immunocytes in BLT mice that spontaneously developed a graft-versus-host-like condition, characterized by alopecia and blepharitis. In diseased animals, we showed an increased PET signal in the liver, attributable to infiltration of activated class II major histocompatibility complex+ T cells. Conclusion: Noninvasive imaging of immune infiltration and activation could thus be of importance for diagnosis and evaluation of treatment of graft-versus-host disease and holds promise for other diseases characterized by inflammation. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  1. The influence of local effects on thermal sensation under non-uniform environmental conditions — Gender differences in thermophysiology, thermal comfort and productivity during convective and radiant cooling

    DEFF Research Database (Denmark)

    Schellen, L.; Loomans, M.G.L.C.; de Wit, M.H.

    2012-01-01

    , thermal comfort and productivity in response to thermal non-uniform environmental conditions. Twenty healthy subjects (10 males and 10 females, age 20–29years) were exposed to two different experimental conditions: a convective cooling situation (CC) and a radiant cooling situation (RC). During...... the experiments physiological responses, thermal comfort and productivity were measured. The results show that under both experimental conditions the actual mean thermal sensation votes significantly differ from the PMV-index; the subjects are feeling colder than predicted. Furthermore, the females are more...... uncomfortable and dissatisfied compared to the males. For females, the local sensations and skin temperatures of the extremities have a significant influence on whole body thermal sensation and are therefore important to consider under non-uniform environmental conditions....

  2. MCF-7 human mammary adenocarcinoma cells exhibit augmented responses to human insulin on a collagen IV surface

    DEFF Research Database (Denmark)

    Listov-Saabye, Nicolai; Jensen, Marianne Blirup; Kiehr, Benedicte

    2009-01-01

    was significantly more mitogenic than native insulin, validating the ability of the assay to identify hypermitogenic human insulin analogs. With MCF-7 cells on a collagen IV surface, the ranking of mitogens was maintained, but fold mitogenic responses and dynamic range and steepness of dose-response curves were...... increased. Also, PI3K pathway activation by insulin was enhanced on a collagen IV surface. This study provided the first determination and ranking of the mitogenic potencies of standard reference compounds in an optimized MCF-7 assay. The optimized MCF-7 assay described here is of relevance for in vitro...... toxicological testing and carcinogenicity safety assessment of new insulin compounds....

  3. Are drug companies living up to their human rights responsibilities? The Merck perspective.

    Directory of Open Access Journals (Sweden)

    Geralyn S Ritter

    2010-09-01

    Full Text Available BACKGROUND TO THE DEBATE: The human rights responsibilities of drug companies have been considered for years by nongovernmental organizations, but were most sharply defined in a report by the UN Special Rapporteur on the right to health, submitted to the United Nations General Assembly in August 2008. The "Human Rights Guidelines for Pharmaceutical Companies in relation to Access to Medicines" include responsibilities for transparency, management, monitoring and accountability, pricing, and ethical marketing, and against lobbying for more protection in intellectual property laws, applying for patents for trivial modifications of existing medicines, inappropriate drug promotion, and excessive pricing. Two years after the release of the Guidelines, the PLoS Medicine Debate asks whether drug companies are living up to their human rights responsibilities. Sofia Gruskin and Zyde Raad from the Harvard School of Public Health say more assessment is needed of such responsibilities; Geralyn Ritter, Vice President of Global Public Policy and Corporate Responsibility at Merck & Co. argues that multiple stakeholders could do more to help States deliver the right to health; and Paul Hunt and Rajat Khosla introduce Mr. Hunt's work as the UN Special Rapporteur on the right to the highest attainable standard of health, regarding the human rights responsibilities of pharmaceutical companies and access to medicines.

  4. Are drug companies living up to their human rights responsibilities? Moving toward assessment.

    Directory of Open Access Journals (Sweden)

    Sofia Gruskin

    2010-09-01

    Full Text Available BACKGROUND TO THE DEBATE: The human rights responsibilities of drug companies have been considered for years by nongovernmental organizations, but were most sharply defined in a report by the UN Special Rapporteur on the right to health, submitted to the United Nations General Assembly in August 2008. The "Human Rights Guidelines for Pharmaceutical Companies in relation to Access to Medicines" include responsibilities for transparency, management, monitoring and accountability, pricing, and ethical marketing, and against lobbying for more protection in intellectual property laws, applying for patents for trivial modifications of existing medicines, inappropriate drug promotion, and excessive pricing. Two years after the release of the Guidelines, the PLoS Medicine Debate asks whether drug companies are living up to their human rights responsibilities. Sofia Gruskin and Zyde Raad from the Harvard School of Public Health say more assessment is needed of such responsibilities; Geralyn Ritter, Vice President of Global Public Policy and Corporate Responsibility at Merck & Co. argues that multiple stakeholders could do more to help States deliver the right to health; and Paul Hunt and Rajat Khosla introduce Mr. Hunt's work as the UN Special Rapporteur on the right to the highest attainable standard of health, regarding the human rights responsibilities of pharmaceutical companies and access to medicines.

  5. Manipulating the content of dynamic natural scenes to characterize response in human MT/MST.

    Science.gov (United States)

    Durant, Szonya; Wall, Matthew B; Zanker, Johannes M

    2011-09-09

    Optic flow is one of the most important sources of information for enabling human navigation through the world. A striking finding from single-cell studies in monkeys is the rapid saturation of response of MT/MST areas with the density of optic flow type motion information. These results are reflected psychophysically in human perception in the saturation of motion aftereffects. We began by comparing responses to natural optic flow scenes in human visual brain areas to responses to the same scenes with inverted contrast (photo negative). This changes scene familiarity while preserving local motion signals. This manipulation had no effect; however, the response was only correlated with the density of local motion (calculated by a motion correlation model) in V1, not in MT/MST. To further investigate this, we manipulated the visible proportion of natural dynamic scenes and found that areas MT and MST did not increase in response over a 16-fold increase in the amount of information presented, i.e., response had saturated. This makes sense in light of the sparseness of motion information in natural scenes, suggesting that the human brain is well adapted to exploit a small amount of dynamic signal and extract information important for survival.

  6. A Return to the Human in Humanism: A Response to Hansen's Humanistic Vision

    Science.gov (United States)

    Lemberger, Matthew E.

    2012-01-01

    In his extension of the humanistic vision, Hansen (2012) recommends that counseling practitioners and scholars adopt operations that are consistent with his definition of a multiple-perspective philosophy. Alternatively, the author of this article believes that Hansen has reduced the capacity of the human to interpret meaning through quantitative…

  7. A Local Response to the Global Human Rights Standard: The "Ubuntu" Perspective on Human Dignity

    Science.gov (United States)

    Murithi, Tim

    2007-01-01

    Some African leaders have made the argument that the promotion of an international human rights standard is a strategy that is used and abused by hypocritical Western governments to justify their intervention into the affairs of African countries. The tacit objective behind this articulation is the desire to avoid an external evaluation or…

  8. Role of Acclimatization in Weather-Related Human Mortality During the Transition Seasons of Autumn and Spring in a Thermally Extreme Mid-Latitude Continental Climate.

    Science.gov (United States)

    de Freitas, Christopher R; Grigorieva, Elena A

    2015-11-26

    Human mortality is closely related to natural climate-determined levels of thermal environmental stress and the resulting thermophysiological strain. Most climate-mortality research has focused on seasonal extremes during winter and summer when mortality is the highest, while relatively little attention has been paid to mortality during the transitional seasons of autumn and spring. The body acclimatizes to heat in the summer and cold in winter and readjusts through acclimatization during the transitions between the two during which time the body experiences the thermophysiological strain of readjustment. To better understand the influences of weather on mortality through the acclimatization process, the aim here is to examine the periods that link very cold and very warms seasons. The study uses the Acclimatization Thermal Strain Index (ATSI), which is a comparative measure of short-term thermophysiological impact on the body. ATSI centers on heat exchange with the body’s core via the respiratory system, which cannot be protected. The analysis is based on data for a major city in the climatic region of the Russian Far East characterized by very hot summers and extremely cold winters. The results show that although mortality peaks in winter (January) and is at its lowest in summer (August), there is not a smooth rise through autumn nor a smooth decline through spring. A secondary peak occurs in autumn (October) with a smaller jump in May. This suggests the acclimatization from warm-to-cold produces more thermophysiological strain than the transition from cold-to-warm. The study shows that ATSI is a useful metric for quantifying the extent to which biophysical adaptation plays a role in increased strain on the body during re-acclimatization and for this reason is a more appropriate climatic indictor than air temperature alone. The work gives useful bioclimatic information on risks involved in transitional seasons in regions characterized by climatic extremes. This

  9. Role of Acclimatization in Weather-Related Human Mortality During the Transition Seasons of Autumn and Spring in a Thermally Extreme Mid-Latitude Continental Climate

    Directory of Open Access Journals (Sweden)

    Christopher R. de Freitas

    2015-11-01

    Full Text Available Human mortality is closely related to natural climate-determined levels of thermal environmental stress and the resulting thermophysiological strain. Most climate-mortality research has focused on seasonal extremes during winter and summer when mortality is the highest, while relatively little attention has been paid to mortality during the transitional seasons of autumn and spring. The body acclimatizes to heat in the summer and cold in winter and readjusts through acclimatization during the transitions between the two during which time the body experiences the thermophysiological strain of readjustment. To better understand the influences of weather on mortality through the acclimatization process, the aim here is to examine the periods that link very cold and very warms seasons. The study uses the Acclimatization Thermal Strain Index (ATSI, which is a comparative measure of short-term thermophysiological impact on the body. ATSI centers on heat exchange with the body’s core via the respiratory system, which cannot be protected. The analysis is based on data for a major city in the climatic region of the Russian Far East characterized by very hot summers and extremely cold winters. The results show that although mortality peaks in winter (January and is at its lowest in summer (August, there is not a smooth rise through autumn nor a smooth decline through spring. A secondary peak occurs in autumn (October with a smaller jump in May. This suggests the acclimatization from warm-to-cold produces more thermophysiological strain than the transition from cold-to-warm. The study shows that ATSI is a useful metric for quantifying the extent to which biophysical adaptation plays a role in increased strain on the body during re-acclimatization and for this reason is a more appropriate climatic indictor than air temperature alone. The work gives useful bioclimatic information on risks involved in transitional seasons in regions characterized by

  10. Measuring response saturation in human MT and MST as a function of motion density.

    Science.gov (United States)

    Durant, Szonya; Furlan, Michele

    2014-07-24

    The human brain areas MT and MST have been studied in great detail using fMRI with regards to their motion processing properties; however, to what extent this corresponds with single cell recordings remains to be fully described. Average response over human MT+ has been shown to increase linearly with motion coherence, similar to single cell responses. In response to motion density some single cell data however suggest a rapid saturation. We ask how the combination of these responses is reflected in the population response. We measured the blood oxygen level dependent (BOLD) response function of MT and MST using a motion density signal, comparing with area V1. We used spatially fixed apertures containing motion stimuli to manipulate the area covered by motion. We found that MT and MST responded above baseline to a very minimal amount of motion and showed a rather flat response to motion density, indicative of saturation. We discuss how this may be related to the size of the receptive fields and inhibitory interactions, although necessarily residual attention effects also need to be considered. We then compared different types of motion and found no difference between coherent and random motion at any motion density, suggesting that when combining response over several motion stimuli covering the visual field, a linear relationship of MT and MST population response as a function of motion coherence might not hold. © 2014 ARVO.

  11. Measuring stress responses in postpartum mothers: perspectives from studies in human and animal populations.

    Science.gov (United States)

    Tu, Mai Thanh; Lupien, Sonia J; Walker, Claire-Dominique

    2005-03-01

    Reduced hypothalamic-pituitary-adrenal (HPA) responses to stress during the last week of pregnancy and lactation have been consistently observed in rat studies. Several contributing factors have been proposed for this phenomenon in lactation, including the suckling stimulus from the pups, hormones (oxytocin and prolactin) and opioids, a decrease in the ability of noradrenaline to potentiate hypothalamic responses and changes in pituitary responsiveness to ACTH secretagogues (AVP and CRF). In contrast to this vast literature using the rat model, only few studies have addressed this issue in the human population. The consensus is that women engaging in breastfeeding activities exhibit reduced anxiety, although the reductions in neuroendocrine and autonomic responses to stressors are variable, in part because of the different nature of the stressors used. Further work is required to investigate how additional factors, such as maternal parity or emotional salience of the stressor can affect stress responsiveness in postpartum women. Here, we review first the findings regarding stress responsiveness during lactation in both rat and human studies, and then discuss potential research avenues and methodological issues that could be the lead to future research protocols in human subjects. Knowing the reciprocal relationship in the mother-infant dyad, it is clear that investigation of the mechanisms regulating stress responses and mental health in postpartum mothers can only be beneficial to the development of the infant.

  12. Tumour-Derived Interleukin-1 Beta Induces Pro-inflammatory Response in Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Alajez, Nehad M; Al-toub, Mashael; Almusa, Abdulaziz

    ’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. Background Over the past several years, significant amount of research has emerged......, the goal of this study was to assess the cellular and molecular changes in MSCs in response to secreted factors present in conditioned media (CM) from a panel of human tumor cell lines covering a spectrum of human cancers (Breast, Prostate, Lung, colon, and head and neck). Research Morphological changes...... with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (~80-99%, and 55...

  13. Comparison of human responses to prototype and standard uniforms using three different human simulation models: HSDA, Scenario_J and Simulink2NM

    National Research Council Canada - National Science Library

    Berglund, L. G; Yokota, M

    2005-01-01

    The human thermal physiological responses of Soldiers in three new prototype clothing systems under development were compared to responses in the current standard duty uniform (STDU) with body armor (BA...

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

    Directory of Open Access Journals (Sweden)

    Vincenzo Paolo Senese

    Full Text Available 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.

  15. Human evolution. Response to Comment on "Human-like hand use in Australopithecus africanus".

    Science.gov (United States)

    Skinner, Matthew M; Stephens, Nicholas B; Tsegai, Zewdi J; Foote, Alexandra C; Nguyen, N Huynh; Gross, Thomas; Pahr, Dieter H; Hublin, Jean-Jacques; Kivell, Tracy L

    2015-06-05

    Almécija and colleagues claim that we apply a simplified understanding of bone functional adaptation and that our results of human-like hand use in Australopithecus africanus are not novel. We argue that our results speak to actual behavior, rather than potential behaviors, and our functional interpretation is well supported by our methodological approach, comparative sample, and previous experimental data. Copyright © 2015, American Association for the Advancement of Science.

  16. Electrophysiological and hemodynamic mismatch responses in rats listening to human speech syllables.

    Science.gov (United States)

    Mahmoudzadeh, Mahdi; Dehaene-Lambertz, Ghislaine; Wallois, Fabrice

    2017-01-01

    Speech is a complex auditory stimulus which is processed according to several time-scales. Whereas consonant discrimination is required to resolve rapid acoustic events, voice perception relies on slower cues. Humans, right from preterm ages, are particularly efficient to encode temporal cues. To compare the capacities of preterms to those observed in other mammals, we tested anesthetized adult rats by using exactly the same paradigm as that used in preterm neonates. We simultaneously recorded neural (using ECoG) and hemodynamic responses (using fNIRS) to series of human speech syllables and investigated the brain response to a change of consonant (ba vs. ga) and to a change of voice (male vs. female). Both methods revealed concordant results, although ECoG measures were more sensitive than fNIRS. Responses to syllables were bilateral, but with marked right-hemispheric lateralization. Responses to voice changes were observed with both methods, while only ECoG was sensitive to consonant changes. These results suggest that rats more effectively processed the speech envelope than fine temporal cues in contrast with human preterm neonates, in whom the opposite effects were observed. Cross-species comparisons constitute a very valuable tool to define the singularities of the human brain and species-specific bias that may help human infants to learn their native language.

  17. Electrophysiological and hemodynamic mismatch responses in rats listening to human speech syllables.

    Directory of Open Access Journals (Sweden)

    Mahdi Mahmoudzadeh

    Full Text Available Speech is a complex auditory stimulus which is processed according to several time-scales. Whereas consonant discrimination is required to resolve rapid acoustic events, voice perception relies on slower cues. Humans, right from preterm ages, are particularly efficient to encode temporal cues. To compare the capacities of preterms to those observed in other mammals, we tested anesthetized adult rats by using exactly the same paradigm as that used in preterm neonates. We simultaneously recorded neural (using ECoG and hemodynamic responses (using fNIRS to series of human speech syllables and investigated the brain response to a change of consonant (ba vs. ga and to a change of voice (male vs. female. Both methods revealed concordant results, although ECoG measures were more sensitive than fNIRS. Responses to syllables were bilateral, but with marked right-hemispheric lateralization. Responses to voice changes were observed with both methods, while only ECoG was sensitive to consonant changes. These results suggest that rats more effectively processed the speech envelope than fine temporal cues in contrast with human preterm neonates, in whom the opposite effects were observed. Cross-species comparisons constitute a very valuable tool to define the singularities of the human brain and species-specific bias that may help human infants to learn their native language.

  18. Electrophysiological and hemodynamic mismatch responses in rats listening to human speech syllables

    Science.gov (United States)

    Dehaene-Lambertz, Ghislaine; Wallois, Fabrice

    2017-01-01

    Speech is a complex auditory stimulus which is processed according to several time-scales. Whereas consonant discrimination is required to resolve rapid acoustic events, voice perception relies on slower cues. Humans, right from preterm ages, are particularly efficient to encode temporal cues. To compare the capacities of preterms to those observed in other mammals, we tested anesthetized adult rats by using exactly the same paradigm as that used in preterm neonates. We simultaneously recorded neural (using ECoG) and hemodynamic responses (using fNIRS) to series of human speech syllables and investigated the brain response to a change of consonant (ba vs. ga) and to a change of voice (male vs. female). Both methods revealed concordant results, although ECoG measures were more sensitive than fNIRS. Responses to syllables were bilateral, but with marked right-hemispheric lateralization. Responses to voice changes were observed with both methods, while only ECoG was sensitive to consonant changes. These results suggest that rats more effectively processed the speech envelope than fine temporal cues in contrast with human preterm neonates, in whom the opposite effects were observed. Cross-species comparisons constitute a very valuable tool to define the singularities of the human brain and species-specific bias that may help human infants to learn their native language. PMID:28291832

  19. Dose-response model of Rocky Mountain spotted fever (RMSF) for human.

    Science.gov (United States)

    Tamrakar, Sushil B; Haas, Charles N

    2011-10-01

    Rickettsia rickettsii is the causative agent of Rocky Mountain spotted fever (RMSF) and is the prototype bacterium in the spotted fever group of rickettsiae, which is found in North, Central, and South America. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through tick bites; however, some cases of aerosol transmission also have been reported. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment, it can be fatal. This article develops dose-response models of different routes of exposure for RMSF in primates and humans. The beta-Poisson model provided the best fit to the dose-response data of aerosol-exposed rhesus monkeys, and intradermally inoculated humans (morbidity as end point of response). The average 50% infectious dose among (ID₅₀) exposed human population, N₅₀, is 23 organisms with 95% confidence limits of 1 to 89 organisms. Similarly, ID₁₀ and ID₂₀ are 2.2 and 5.0, respectively. Moreover, the data of aerosol-exposed rhesus monkeys and intradermally inoculated humans could be pooled. This indicates that the dose-response models fitted to different data sets are not significantly different and can be described by the same relationship. © 2011 Society for Risk Analysis.

  20. Histologic Evaluation of Human Pulp Response to Total Etch and Self Etch Adhesive Systems

    OpenAIRE

    Malekipour, Mohammad Reza; Razavi, Sayed Mohammad; Khazaei, Saber; Kazemi, Shantia; Behnamanesh, Maryam; Shirani, Farzaneh

    2013-01-01

    Background To investigate pulp response to the application of two types adhesive systems (total-etch and self-etch) in human premolar teeth. Materials and Methods Cavities limited to enamel walls in all margins with 2.5 mm depth were prepared on buccal surfaces of thirty three human premolars. The cavities were treated with the following adhesive. Single Bond (SB) and Prompt L-Pop (PLP). The teeth were extracted after 30 days and prepared due to histological technique. Results Pulp responses ...

  1. CORPORATE SOCIAL RESPONSIBILITY AS A COMPETITIVE STRATEGY: THE CASE OF HUMAN COMPANY

    Directory of Open Access Journals (Sweden)

    Daniela Castro Murillo

    2013-07-01

    Full Text Available Human Company, a 100% Costa Rican business, through its brand Eco Sunrise has achieved to produce biodegradable goods under a socially responsible approach. This paper is aimed at evaluating how these practices influence the Company’s competitiveness levels using the PRISMA method and the CINBAGE matrix. Therefore, the general objective is to determine whether Corporate Social Responsibility (CSR is a competitive strategy for Human Company, for which the Company must identify advantages and obstacles faced by SMEs in regards to CSR, evaluate each of the areas comprising the Company’s CSR, quantify the Company´s competitiveness, and determine how CSR influences competitiveness.

  2. A cholinergic contribution to the circulatory responses evoked at the onset of handgrip exercise in humans

    DEFF Research Database (Denmark)

    Vianna, Lauro C; Fadel, Paul J; Secher, Niels H

    2015-01-01

    A cholinergic (muscarinic) contribution to the initial circulatory response to exercise in humans remains controversial. Herein, we posit that this may be due to exercise mode with a cholinergic contribution being important during isometric handgrip exercise, where the hyperemic response of the m......A cholinergic (muscarinic) contribution to the initial circulatory response to exercise in humans remains controversial. Herein, we posit that this may be due to exercise mode with a cholinergic contribution being important during isometric handgrip exercise, where the hyperemic response...... of the muscle is relatively small compared with the onset of leg cycling, where a marked increase in muscle blood flow rapidly occurs as a consequence of multiple redundant mechanisms. We recorded blood pressure (BP; brachial artery), stroke volume (pulse contour analysis), cardiac output, and systemic vascular...

  3. Integrative genomic analysis of the human immune response to influenza vaccination.

    Science.gov (United States)

    Franco, Luis M; Bucasas, Kristine L; Wells, Janet M; Niño, Diane; Wang, Xueqing; Zapata, Gladys E; Arden, Nancy; Renwick, Alexander; Yu, Peng; Quarles, John M; Bray, Molly S; Couch, Robert B; Belmont, John W; Shaw, Chad A

    2013-07-16

    Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI:http://dx.doi.org/10.7554/eLife.00299.001.

  4. Review on modeling heat transfer and thermoregulatory responses in human body.

    Science.gov (United States)

    Fu, Ming; Weng, Wenguo; Chen, Weiwang; Luo, Na

    2016-12-01

    Several mathematical models of human thermoregulation have been developed, contributing to a deep understanding of thermal responses in different thermal conditions and applications. In these models, the human body is represented by two interacting systems of thermoregulation: the controlling active system and the controlled passive system. This paper reviews the recent research of human thermoregulation models. The accuracy and scope of the thermal models are improved, for the consideration of individual differences, integration to clothing models, exposure to cold and hot conditions, and the changes of physiological responses for the elders. The experimental validated methods for human subjects and manikin are compared. The coupled method is provided for the manikin, controlled by the thermal model as an active system. Computational Fluid Dynamics (CFD) is also used along with the manikin or/and the thermal model, to evaluate the thermal responses of human body in various applications, such as evaluation of thermal comfort to increase the energy efficiency, prediction of tolerance limits and thermal acceptability exposed to hostile environments, indoor air quality assessment in the car and aerospace industry, and design protective equipment to improve function of the human activities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Discrimination of human and dog faces and inversion responses in domestic dogs (Canis familiaris).

    Science.gov (United States)

    Racca, Anaïs; Amadei, Eleonora; Ligout, Séverine; Guo, Kun; Meints, Kerstin; Mills, Daniel

    2010-05-01

    Although domestic dogs can respond to many facial cues displayed by other dogs and humans, it remains unclear whether they can differentiate individual dogs or humans based on facial cues alone and, if so, whether they would demonstrate the face inversion effect, a behavioural hallmark commonly used in primates to differentiate face processing from object processing. In this study, we first established the applicability of the visual paired comparison (VPC or preferential looking) procedure for dogs using a simple object discrimination task with 2D pictures. The animals demonstrated a clear looking preference for novel objects when simultaneously presented with prior-exposed familiar objects. We then adopted this VPC procedure to assess their face discrimination and inversion responses. Dogs showed a deviation from random behaviour, indicating discrimination capability when inspecting upright dog faces, human faces and object images; but the pattern of viewing preference was dependent upon image category. They directed longer viewing time at novel (vs. familiar) human faces and objects, but not at dog faces, instead, a longer viewing time at familiar (vs. novel) dog faces was observed. No significant looking preference was detected for inverted images regardless of image category. Our results indicate that domestic dogs can use facial cues alone to differentiate individual dogs and humans and that they exhibit a non-specific inversion response. In addition, the discrimination response by dogs of human and dog faces appears to differ with the type of face involved.

  6. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  7. Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers.

    Directory of Open Access Journals (Sweden)

    Jen-Tsan Chi

    2006-03-01

    Full Text Available Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases.We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use.The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer.

  8. Strategic human resource management and corporate social responsibility: Evidence from Emerging Markets

    OpenAIRE

    Rosolen, Talita; MacLennan, Maria Laura Ferranty

    2016-01-01

    Corporate social responsibility practices are increasingly being adopted and legitimized in business and they impact the strategic and operational levels in various areas. The integration of these criteria and practices in the strategic management involves many factors, and human resource management is an essential aspect for the accomplishment of such initiative. Thus, this paper associates the relationship among corporate social responsibility (CSR) various dimensions (strategic, ethical, s...

  9. Inter- and intra-individual covariations of hemodynamic and oscillatory gamma responses in the human cortex

    Directory of Open Access Journals (Sweden)

    Tino Zaehle

    2009-06-01

    Full Text Available The time course of local field potentials displaying typical discharge frequencies in the gamma frequency range highly correlates with the BOLD signal in response to rotating checkerboard stimuli in animals. In humans, oscillatory gamma-band responses (GBRs show strong inter-individual variations in frequency and amplitude but considerable intra-individual reliability indicating that individual gamma activity reflects a personal trait. While the functional role of these GBRs is still debated, investigations combining EEG–fMRI measurements provide a tool to obtain further insights into the underlying functional architecture of the human brain and will shed light onto the understanding of the dynamic relation between the BOLD signal and the properties of the electrical activity recorded on the scalp. We investigated the relation between the hemodynamic response and evoked gamma-band response (eGBR to visual stimulation. We tested the hypothesis that the amplitude of human eGBRs and BOLD responses covary intra-individually as a function of stimulation as well as inter-individually as a function of gamma-trait. 17 participants performed visual discrimination tasks during separate EEG and fMRI recordings. Results revealed that visual stimuli that evoked high GBRs also elicited strong BOLD responses in the human V1/V2 complex. Furthermore, inter-individual variations of BOLD responses to visual stimuli in the bilateral primary (Area 17 and secondary (Area V5/MT visual cortex and the right hippocampal formation were correlated with the individual gamma-trait of the subjects. The present study further supports the notion that neural oscillations in the gamma frequency range are involved in the cascade of neural processes that underlie the hemodynamic responses measured with fMRI.

  10. Multifactorial analysis of human blood cell responses to clinical total body irradiation

    Science.gov (United States)

    Yuhas, J. M.; Stokes, T. R.; Lushbaugh, C. C.

    1972-01-01

    Multiple regression analysis techniques are used to study the effects of therapeutic radiation exposure, number of fractions, and time on such quantal responses as tumor control and skin injury. The potential of these methods for the analysis of human blood cell responses is demonstrated and estimates are given of the effects of total amount of exposure and time of protraction in determining the minimum white blood cell concentration observed after exposure of patients from four disease groups.

  11. Analysis of DNA-damage response to ionizing radiation in serum-shock synchronized human fibroblasts

    OpenAIRE

    Corra', Samantha; Salvadori, Riccardo; Bee, Leonardo; Barbieri, Vito; Mognato, Maddalena

    2017-01-01

    Many aspects of cellular physiology, including cellular response to genotoxic stress, are related to the circadian rhythmicity induced by the molecular clock. The current study investigated if the cellular response to DNA damage is in relation to endogenous expression levels of the PER2 protein, a key component of the molecular regulatory system that confers rhythmicity in mammalian cells. Human normal fibroblasts (CCD-34Lu) were subjected to serum shock to induce circadian oscillations of th...

  12. Human non-visual responses to simultaneous presentation of blue and red monochromatic light.

    OpenAIRE

    Papamichael, C.; Skene, DJ; Revell, VL

    2012-01-01

    Blue light sensitivity of melatonin suppression and subjective mood and alertness responses in humans is recognised as being melanopsin based. Observations that long wavelength (red) light can potentiate responses to subsequent short wavelength (blue) light have been attributed to the bistable nature of melanopsin whereby it forms stable associations with both 11-cis and alltrans isoforms of retinaldehyde and uses light to transition between these states. The current study examined the effect...

  13. Chemokine Secretion of Human Cells in Response to Toxoplasma gondii Infection

    OpenAIRE

    Denney, Carolyn F.; Eckmann, Lars; Reed, Sharon L.

    1999-01-01

    The ubiquitous protozoan parasite Toxoplasma gondii is a major cause of morbidity and mortality in neonates and immunocompromised hosts. Both acute invasion and reactivation of latent infection result in an inflammatory reaction with lymphocytes, macrophages, and neutrophils. The mechanisms responsible for triggering the local host response to toxoplasmosis are not fully understood. Infection of monolayers of human HeLa epithelial cells and fibroblasts with T. gondii resulted in a marked incr...

  14. Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Rocke, David [Univ. of California, Davis, CA (United States)

    2016-08-01

    In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

  15. Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology.

    Science.gov (United States)

    Wanner, Samuel Penna; Prímola-Gomes, Thales Nicolau; Pires, Washington; Guimarães, Juliana Bohnen; Hudson, Alexandre Sérvulo Ribeiro; Kunstetter, Ana Cançado; Fonseca, Cletiana Gonçalves; Drummond, Lucas Rios; Damasceno, William Coutinho; Teixeira-Coelho, Francisco

    2015-01-01

    Rats are used worldwide in experiments that aim to investigate the physiological responses induced by a physical exercise session. Changes in body temperature regulation, which may affect both the performance and the health of exercising rats, are evident among these physiological responses. Despite the universal use of rats in biomedical research involving exercise, investigators often overlook important methodological issues that hamper the accurate measurement of clear thermoregulatory responses. Moreover, much debate exists regarding whether the outcome of rat experiments can be extrapolated to human physiology, including thermal physiology. Herein, we described the impact of different exercise intensities, durations and protocols and environmental conditions on running-induced thermoregulatory changes. We focused on treadmill running because this type of exercise allows for precise control of the exercise intensity and the measurement of autonomic thermoeffectors associated with heat production and loss. Some methodological issues regarding rat experiments, such as the sites for body temperature measurements and the time of day at which experiments are performed, were also discussed. In addition, we analyzed the influence of a high body surface area-to-mass ratio and limited evaporative cooling on the exercise-induced thermoregulatory responses of running rats and then compared these responses in rats to those observed in humans. Collectively, the data presented in this review represent a reference source for investigators interested in studying exercise thermoregulation in rats. In addition, the present data indicate that the thermoregulatory responses of exercising rats can be extrapolated, with some important limitations, to human thermal physiology.

  16. Regulating corporate social and human rights responsibilities at the UN plane

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2009-01-01

    businesses' impact on human rights. The pattern of using these forms suggests an institutionalisation of reflexive regulation as a regulatory process drawing on public-private regulation, and of an emerging UN based 'Global Administrative Law' in order to meet regulatory challenges in living up to the human......Globalisation's unprecedented growth and transborder activities of business coupled with increasing awareness of the impact of business on societies and human rights has resulted in demands for the international society to regulate corporate social and human rights responsibilities. This not only...... challenges traditional notions of duty bearers under international law, but also calls for novel approaches for the United Nations (UN) to implement central parts of the Charter's human rights aims and to address corporate behaviour in a state-centred international law-making order that lacks the willingness...

  17. Inverted Encoding Models of Human Population Response Conflate Noise and Neural Tuning Width.

    Science.gov (United States)

    Liu, Taosheng; Cable, Dylan; Gardner, Justin L

    2018-01-10

    Channel-encoding models offer the ability to bridge different scales of neuronal measurement by interpreting population responses, typically measured with BOLD imaging in humans, as linear sums of groups of neurons (channels) tuned for visual stimulus properties. Inverting these models to form predicted channel responses from population measurements in humans seemingly offers the potential to infer neuronal tuning properties. Here, we test the ability to make inferences about neural tuning width from inverted encoding models. We examined contrast invariance of orientation selectivity in human V1 (both sexes) and found that inverting the encoding model resulted in channel response functions that became broader with lower contrast, thus apparently violating contrast invariance. Simulations showed that this broadening could be explained by contrast-invariant single-unit tuning with the measured decrease in response amplitude at lower contrast. The decrease in response lowers the signal-to-noise ratio of population responses that results in poorer population representation of orientation. Simulations further showed that increasing signal to noise makes channel response functions less sensitive to underlying neural tuning width, and in the limit of zero noise will reconstruct the channel function assumed by the model regardless of the bandwidth of single units. We conclude that our data are consistent with contrast-invariant orientation tuning in human V1. More generally, our results demonstrate that population selectivity measures obtained by encoding models can deviate substantially from the behavior of single units because they conflate neural tuning width and noise and are therefore better used to estimate the uncertainty of decoded stimulus properties.SIGNIFICANCE STATEMENT It is widely recognized that perceptual experience arises from large populations of neurons, rather than a few single units. Yet, much theory and experiment have examined links between single

  18. Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.

    Science.gov (United States)

    Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Łukjanow, Magdalena

    2017-04-01

    Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non‑homologous end‑joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC‑based clinical protocols.

  19. Human CD4+ T Helper Cell Responses after Tick-Borne Encephalitis Vaccination and Infection.

    Directory of Open Access Journals (Sweden)

    Judith H Aberle

    Full Text Available Tick-borne encephalitis virus (TBEV is a human-pathogenic flavivirus that is endemic in large parts of Europe and Asia and causes severe neuroinvasive illness. A formalin-inactivated vaccine induces strong neutralizing antibody responses and confers protection from TBE disease. CD4+ T cell responses are essential for neutralizing antibody production, but data on the functionalities of TBEV-specific CD4+ T cells in response to vaccination or infection are lacking. This study provides a comprehensive analysis of the cytokine patterns of CD4+ T cell responses in 20 humans after TBE vaccination in comparison to those in 18 patients with TBEV infection. Specifically, Th1-specific cytokines (IFN-γ, IL-2, TNF-α, CD40 ligand and the Th1 lineage-specifying transcription factor Tbet were determined upon stimulation with peptides covering the TBEV structural proteins contained in the vaccine (C-capsid, prM/M-membrane and E-envelope. We show that TBEV-specific CD4+ T cell responses are polyfunctional, but the cytokine patterns after vaccination differed from those after infection. TBE vaccine responses were characterized by lower IFN-γ responses and high proportions of TNF-α+IL-2+ cells. In vaccine-induced responses-consistent with the reduced IFN-γ expression patterns-less than 50% of TBEV peptides were detected by IFN-γ+ cells as compared to 96% detected by IL-2+ cells, indicating that the single use of IFN-γ as a read-out strongly underestimates the magnitude and breadth of such responses. The results provide important insights into the functionalities of CD4+ T cells that coordinate vaccine responses and have direct implications for future studies that address epitope specificity and breadth of these responses.

  20. Brain Response to a Humanoid Robot in Areas Implicated in the Perception of Human Emotional Gestures

    Science.gov (United States)

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

    2010-01-01

    Background The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. Methodology Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. Principal Findings Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. Conclusions Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. Significance Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions. PMID:20657777

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

    Directory of Open Access Journals (Sweden)

    Thierry Chaminade

    2010-07-01

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

  2. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.

    Science.gov (United States)

    Abegglen, Lisa M; Caulin, Aleah F; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S; Kiso, Wendy K; Schmitt, Dennis L; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T; Maley, Carlo C; Schiffman, Joshua D

    2015-11-03

    Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis

  3. Brain Imaging of Human Sexual Response : Recent Developments and Future Directions

    NARCIS (Netherlands)

    Ruesink, Gerben B; Georgiadis, Janniko R

    2017-01-01

    Purpose of Review: The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Recent Findings: Stable patterns of brain activation have been established for

  4. Immunomodulatory effects of streptococcus suis capsule type on human dendritic cell responses, phagocytosis and intracellular survival.

    NARCIS (Netherlands)

    Meijerink, M.; Ferrando, M.L.; Lammers, G.; Taverne, N.; Smith, H.E.; Wells, J.

    2012-01-01

    Streptococcus suis is a major porcine pathogen of significant commercial importance worldwide and an emerging zoonotic pathogen of humans. Given the important sentinel role of mucosal dendritic cells and their importance in induction of T cell responses we investigated the effect of different S.

  5. Acinar injury and early cytokine response in human acute biliary pancreatitis.

    Science.gov (United States)

    Jakkampudi, Aparna; Jangala, Ramaiah; Reddy, Ratnakar; Mitnala, Sasikala; Rao, G Venkat; Pradeep, Rebala; Reddy, D Nageshwar; Talukdar, Rupjyoti

    2017-11-10

    Clinical acute pancreatitis (AP) is marked by an early phase of systemic inflammatory response syndrome (SIRS) with multiorgan dysfunction (MODS), and a late phase characterized by sepsis with MODS. However, the mechanisms of acinar injury in human AP and the associated systemic inflammation are not clearly understood. This study, for the first time, evaluated the early interactions of bile acid induced human pancreatic acinar injury and the resulting cytokine response. We exposed freshly procured resected human pancreata to taurolithocolic acid (TLCS) and evaluated for acinar injury, cytokine release and interaction with peripheral blood mononuclear cells (PBMCs). We observed autophagy in acinar cells in response to TLCS exposure. There was also time-dependent release of IL-6, IL-8 and TNF-α from the injured acini that resulted in activation of PBMCs. We also observed that cytokines secreted by activated PBMCs resulted in acinar cell apoptosis and further cytokine release from them. Our data suggests that the earliest immune response in human AP originates within the acinar cell itself, which subsequently activates circulating PBMCs leading to SIRS. These findings need further detailed evaluation so that specific therapeutic targets to curb SIRS and resulting early adverse outcomes could be identified and tested.

  6. A System Dynamics Model to Predict the Human Monocyte Response to Endotoxins

    Directory of Open Access Journals (Sweden)

    Enrique Álvarez

    2017-08-01

    Full Text Available System dynamics is a powerful tool that allows modeling of complex and highly networked systems such as those found in the human immune system. We have developed a model that reproduces how the exposure of human monocytes to lipopolysaccharides (LPSs induces an inflammatory state characterized by high production of tumor necrosis factor alpha (TNFα, which is rapidly modulated to enter into a tolerant state, known as endotoxin tolerance (ET. The model contains two subsystems with a total of six states, seven flows, two auxiliary variables, and 14 parameters that interact through six differential and nine algebraic equations. The parameters were estimated and optimized to obtain a model that fits the experimental data obtained from human monocytes treated with various LPS doses. In contrast to publications on other animal models, stimulation of human monocytes with super-low-dose LPSs did not alter the response to a second LPSs challenge, neither inducing ET, nor enhancing the inflammatory response. Moreover, the model confirms the low production of TNFα and increased levels of C–C motif ligand 2 when monocytes exhibit a tolerant state similar to that of patients with sepsis. At present, the model can help us better understand the ET response and might offer new insights on sepsis diagnostics and prognosis by examining the monocyte response to endotoxins in patients with sepsis.

  7. Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Hansen, Adam E; Pedersen, Simon

    2011-01-01

    To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how...... pharmacological agents may modulate cerebral hemodynamic and thereby possibly the BOLD signal....

  8. Different pharmacological responses of atrium and ventricle: Studies with human cardiac tissue

    NARCIS (Netherlands)

    X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); E. Bos (Egbert); P.R. Saxena (Pramod Ranjan)

    1994-01-01

    textabstractIt has been recently reported that 5-hydroxytryptamine (5-HT) increases force of contraction in atrial tissue but not in ventricular tissue. In the present study with trabeculae obtained from non-diseased human hearts, we investigated whether this difference in the contractile response

  9. Convergence in probiotic Lactobacillus gut-adaptive responses in humans and mice

    NARCIS (Netherlands)

    Marco, M.; Vries, de M.C.; Wels, M.W.W.; Molenaar, D.; Mangell, P.; Ahrne, S.; Vos, de W.M.; Vaughan, E.E.; Kleerebezem, M.

    2010-01-01

    Probiotic bacteria provide unique opportunities to study the global responses and molecular mechanisms underlying the effects of gut-associated microorganisms in the human digestive tract. In this study, we show by comparative transcriptome analysis using DNA microarrays that the established

  10. CargoVibes: human response to vibration due to freight rail traffic

    NARCIS (Netherlands)

    Waddington, D.; Woodcock, J.; Smith, M.G.; Janssen, S.A.; Persson Waye, K.

    2015-01-01

    The aim of this paper is to present an overview of the research concerning human response to vibration conducted in the EU FP7 CargoVibes project. The European Union-funded project CargoVibes involved 10 partners from 8 nations and ran from April 2011 to April 2014. The project was concerned with

  11. Grassroots Responsiveness to Human Rights Abuse: History of the Washtenaw Interfaith Coalition for Immigrant Rights

    Science.gov (United States)

    Sanders, Laura; Martinez, Ramiro; Harner, Margaret; Harner, Melanie; Horner, Pilar; Delva, Jorge

    2013-01-01

    The purpose of this article is to discuss how a community agency based in Washtenaw County, the Washtenaw Interfaith Coalition for Immigration Rights (WICIR), emerged in response to increasing punitive immigration practices and human rights abuses toward the Latino community. The article discusses how WICIR is engaged in advocacy, community…

  12. Lack of effort or lack of ability? Robot failures and human perception of agency and responsibility

    NARCIS (Netherlands)

    Woerdt, S. van der; Haselager, W.F.G.

    2017-01-01

    Research on human interaction has shown that considering an agent's actions related to either effort or ability can have important consequences for attributions of responsibility. In this study, these findings have been applied in a HRI context, investigating how participants' interpretation of a

  13. Alveolar recruitment of ficolin-3 in response to acute pulmonary inflammation in humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Munthe-Fog, Lea

    2016-01-01

    acute lung and systemic inflammation induce recruitment of lectins in humans. METHODS: Fifteen healthy volunteers received LPS intravenously (IV) or in a lung subsegment on two different occasions. Volunteers were evaluated by consecutive blood samples and by bronchoalveolar lavage 2, 4, 6, 8, or 24h...... acute phase response with an increase in CRP (precruitment...

  14. Ingested human insulin inhibits the mosquito NF-¿B-dependent immune response to Plasmodium falciparum

    Science.gov (United States)

    We showed previously that ingested human insulin activates the insulin/IGF-1 signaling pathway in Anopheles stephensi and increases the susceptibility of these mosquitoes to Plasmodium falciparum. In other organisms insulin can alter immune responsiveness through regulation of NF-kB transcription fa...

  15. Barcoding heat shock proteins to human diseases : looking beyond the heat shock response

    NARCIS (Netherlands)

    Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H.

    There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR) - and thus generally restoring the disturbed protein homeostasis associated with such diseases - has often been suggested as a

  16. Proteomic Assessment of Biochemical Pathways That Are Critical to Nickel-Induced Toxicity Responses in Human Epithelial Cells

    Science.gov (United States)

    Understanding the mechanisms underlying toxicity initiated by nickel, a ubiquitous environmental contaminant and known human carcinogen is necessary for proper assessment of its risks to human and environment. Among a variety of toxic mechanisms, disruption of protein responses a...

  17. [Affective behavioural responses by dogs to tactile human-dog interactions].

    Science.gov (United States)

    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

  18. Human thermal sensation: frequency response to sinusoidal stimuli at the surface of the skin

    DEFF Research Database (Denmark)

    Ring, J.W.; de Dear, Richard; Melikov, Arsen Krikor

    1993-01-01

    . A psychosensory intensity (PSI) model has been developed to relate experimentally derived sensation data to simulated cutaneous thermoreceptor responses to the temperature ramp-plateaux and step stimuli applied to the skin surface by thermodes. From the point of view of signal processing, a natural extension...... function. This function is then compared with the functional form found in two experiments where the stimuli were pulsating airflows of differing frequency. The PSI model seems to simulate well the form of the response of the human skin system to varying temperature changes of a whole range of frequencies...... of this approach is to ask what the response would be to sinusoidally varying stimuli of differing frequencies, or, in other words, what would be the frequency response of this skin system? The purpose of this paper is to extend the PSI model and apply these sinusoids to it and hence find the frequency response...

  19. Influence of Pause Duration and Nod Response Timing in Dialogue between Human and Communication Robot

    Science.gov (United States)

    Takasugi, Shoji; Yoshida, Shohei; Okitsu, Kengo; Yokoyama, Masanori; Yamamoto, Tomohito; Miyake, Yoshihiro

    The purpose of this study is to clarify the influence from timing of utterance and body motion in dialogue between human and robot. We controlled pause duration and nod response timing in robot-side, and analyzed impression of communication in human-side by using Scheffe's Paired Comparison method. The results revealed that the impression of communication significantly modified by changing the pause duration and nod response timing. And, timing pattern of the impression altered diversely in elderly people than in younger, indicating that elderly generation uses various timing control mechanisms. From these results, it was suggested that timing control and impression of communication are mutually influenced, and this mechanism is thought to be useful to realize human-robot communication system for elderly generation.

  20. Identification of genes responsive to solar simulated UV radiation in human monocyte-derived dendritic cells.

    Directory of Open Access Journals (Sweden)

    Hortensia de la Fuente

    Full Text Available Ultraviolet (UV irradiation has profound effects on the skin and the systemic immune system. Several effects of UV radiation on Dendritic cells (DCs functions have been described. However, gene expression changes induced by UV radiation in DCs have not been addressed before. In this report, we irradiated human monocyte-derived DCs with solar-simulated UVA/UVB and analyzed regulated genes on human whole genome arrays. Results were validated by RT-PCR and further analyzed by Gene Set Enrichment Analysis (GSEA. Solar-simulated UV radiation up-regulated expression of genes involved in cellular stress and inflammation, and down-regulated genes involved in chemotaxis, vesicular transport and RNA processing. Twenty four genes were selected for comparison by RT-PCR with similarly treated human primary keratinocytes and human melanocytes. Several genes involved in the regulation of the immune response were differentially regulated in UVA/UVB irradiated human monocyte-derived DCs, such as protein tyrosine phosphatase, receptor type E (PTPRE, thrombospondin-1 (THBS1, inducible costimulator ligand (ICOSL, galectins, Src-like adapter protein (SLA, IL-10 and CCR7. These results indicate that UV-exposure triggers the regulation of a complex gene repertoire involved in human-DC-mediated immune responses.

  1. Statistical Analysis of Human Body Movement and Group Interactions in Response to Music

    Science.gov (United States)

    Desmet, Frank; Leman, Marc; Lesaffre, Micheline; de Bruyn, Leen

    Quantification of time series that relate to physiological data is challenging for empirical music research. Up to now, most studies have focused on time-dependent responses of individual subjects in controlled environments. However, little is known about time-dependent responses of between-subject interactions in an ecological context. This paper provides new findings on the statistical analysis of group synchronicity in response to musical stimuli. Different statistical techniques were applied to time-dependent data obtained from an experiment on embodied listening in individual and group settings. Analysis of inter group synchronicity are described. Dynamic Time Warping (DTW) and Cross Correlation Function (CCF) were found to be valid methods to estimate group coherence of the resulting movements. It was found that synchronicity of movements between individuals (human-human interactions) increases significantly in the social context. Moreover, Analysis of Variance (ANOVA) revealed that the type of music is the predominant factor in both the individual and the social context.

  2. The effect of feeding frequency on insulin and ghrelin responses in human subjects

    DEFF Research Database (Denmark)

    Solomon, Thomas; Chambers, Edward S; Jeukendrup, Asker E

    2008-01-01

    Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin...... and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2)years, body mass 75.7 (SEM 3.2) kg and BMI 23.8 (SEM 0.8) kg/m(2). Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency(two) meal ingestion (LOFREQ......(MEAL)); high-frequency (twelve) meal ingestion (HIFREQ(MEAL)). Meals were equi-energetic within trials,consisting of 64% carbohydrate, 23% fat and 13% protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between...

  3. Could be the swine responsible of transmission to the humans of Dientamoeba fragilis infection?

    Directory of Open Access Journals (Sweden)

    Daniele Crotti

    2011-03-01

    Full Text Available Dientamoeba fragilis, atypical protozoon because “flagellate without flagella” but amoeba-like, of whom we know only the trophozoitic stage (an so its brittleness outside intestinal tract, is a frequent responsible of intestinal human infections, worldwide, and some authors relate that D. fragilis is the most frequent protozoon and parasite that can infects humans. Actually we don’t know a sure potential “reservoir” in animals who are strictly in contact with humans, and it is difficult to understand its epidemiological chain, otherwise the transmissions to humans and from humans to humans. For all these reasons we performed another study on subjects of swine breedings, and among people who work in these breedings, that are in direct contact or not with pigs. Using standardized methodologies, we analyzed 224 faecal specimens of swine and 15 human specimens.We use for identification of D. fragilis the Giemsa stain.These were the results: D. fragilis was observed in 50.9% of pigs and 20% among humans (30% in workers strictly in contact with breedings and pigs, 0% in familiars or other without a closed contact with swines. Other commensal protozoa were observed with variable associations, but in this article we want to analyze the possible transmission from this pigs to humans (and for us this protozoon is undoubtedly a “reservoir” of D. fragilis for humans, and underline two aspects: for the research of this protozoon, standard procedures area mandatory, with a permanent stain, as Giemsa stain, is necessary, and in all humans with various intestinal infections or troubles, particularly “irritable bowel syndrome” (or similar ones, the specimens must be analyzed for D. fragilis. At least we think that in the near future molecular studies are important for confirming this our observations, and for verifying eventual and probable differences inside genotypes of this very suggestive protozoon, that until now present not rarely

  4. Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices.

    Science.gov (United States)

    Switalla, S; Lauenstein, L; Prenzler, F; Knothe, S; Förster, C; Fieguth, H-G; Pfennig, O; Schaumann, F; Martin, C; Guzman, C A; Ebensen, T; Müller, M; Hohlfeld, J M; Krug, N; Braun, A; Sewald, K

    2010-08-01

    Prediction of lung innate immune responses is critical for developing new drugs. Well-established immune modulators like lipopolysaccharides (LPS) can elicit a wide range of immunological effects. They are involved in acute lung diseases such as infections or chronic airway diseases such as COPD. LPS has a strong adjuvant activity, but its pyrogenicity has precluded therapeutic use. The bacterial lipopeptide MALP-2 and its synthetic derivative BPPcysMPEG are better tolerated. We have compared the effects of LPS and BPPcysMPEG on the innate immune response in human precision-cut lung slices. Cytokine responses were quantified by ELISA, Luminex, and Meso Scale Discovery technology. The initial response to LPS and BPPcysMPEG was marked by coordinated and significant release of the mediators IL-1β, MIP-1β, and IL-10 in viable PCLS. Stimulation of lung tissue with BPPcysMPEG, however, induced a differential response. While LPS upregulated IFN-γ, BPPcysMPEG did not. This traces back to their signaling pathways via TLR4 and TLR2/6. The calculated exposure doses selected for LPS covered ranges occurring in clinical studies with human beings. Correlation of obtained data with data from human BAL fluid after segmental provocation with endotoxin showed highly comparable effects, resulting in a coefficient of correlation >0.9. Furthermore, we were interested in modulating the response to LPS. Using dexamethasone as an immunosuppressive drug for anti-inflammatory therapy, we found a significant reduction of GM-CSF, IL-1β, and IFN-γ. The PCLS-model offers the unique opportunity to test the efficacy and toxicity of biological agents intended for use by inhalation in a complex setting in humans. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, Mykyta V., E-mail: sokolovm@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Irina V., E-mail: ipanyutinv@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Igor G., E-mail: igorp@helix.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Neumann, Ronald D., E-mail: rneumann@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States)

    2011-05-10

    One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

  6. The behaviour of satellite cells in response to exercise: what have we learned from human studies?

    DEFF Research Database (Denmark)

    Kadi, Fawzi; Olsen, Steen Schytte

    2005-01-01

    Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards...... the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei...... and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation...

  7. In vivo optical imaging of physiological responses to photostimulation in human photoreceptors

    CERN Document Server

    Hillmann, Dierck; Pfäffle, Clara; Sudkamp, Helge; Franke, Gesa; Hüttmann, Gereon

    2016-01-01

    Non-invasive functional imaging of molecular and cellular processes of vision is expected to have immense impact on research and clinical diagnostics. Although suitable intrinsic optical signals (IOS) have been observed ex vivo and in immobilized animals in vivo, it was so far not possible to obtain convincing IOS of photoreceptor activity in humans in vivo. Here, we observed spatially and temporally clearly resolved changes in the optical path length of the photoreceptor outer segment as response to an optical stimulus in living human. To obtain these changes, we evaluated phase data of a parallelized and computationally aberration-corrected optical coherence tomography (OCT) system. The non-invasive detection of optical path length changes shows the neuronal photoreceptor activity of single cones in living human retina, and, more importantly, it provides a new diagnostic option in ophthalmology and neurology and could give new insights into visual phototransduction in humans.

  8. Timing of single-neuron and local field potential responses in the human medial temporal lobe.

    Science.gov (United States)

    Rey, Hernan Gonzalo; Fried, Itzhak; Quian Quiroga, Rodrigo

    2014-02-03

    The relationship between the firing of single cells and local field potentials (LFPs) has received increasing attention, with studies in animals [1-11] and humans [12-14]. Recordings in the human medial temporal lobe (MTL) have demonstrated the existence of neurons with selective and invariant responses [15], with a relatively late but precise response onset around 300 ms after stimulus presentation [16-18] and firing only upon conscious recognition of the stimulus [19]. This represents a much later onset than expected from direct projections from inferotemporal cortex [16, 18]. The neural mechanisms underlying this onset remain unclear. To address this issue, we performed a joint analysis of single-cell and LFP responses during a visual recognition task. Single-neuron responses were preceded by a global LFP deflection in the theta range. In addition, there was a local and stimulus-specific increase in the single-trial gamma power. These LFP responses correlated with conscious recognition. The timing of the neurons' firing was phase locked to these LFP responses. We propose that whereas the gamma phase locking reflects the activation of local networks encoding particular recognized stimuli, the theta phase locking reflects a global activation that provides a temporal window for processing consciously perceived stimuli in the MTL. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Intestinal organoids model human responses to infection by commensal and Shiga toxin producing Escherichia coli.

    Science.gov (United States)

    Karve, Sayali S; Pradhan, Suman; Ward, Doyle V; Weiss, Alison A

    2017-01-01

    Infection with Shiga toxin (Stx) producing Escherichia coli O157:H7 can cause the potentially fatal complication hemolytic uremic syndrome, and currently only supportive therapy is available. Lack of suitable animal models has hindered study of this disease. Induced human intestinal organoids (iHIOs), generated by in vitro differentiation of pluripotent stem cells, represent differentiated human intestinal tissue. We show that iHIOs with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses. Commensal and O157:H7 introduced into the iHIO lumen replicated rapidly achieving high numbers. Commensal E. coli did not cause damage, and were completely contained within the lumen, suggesting defenses, such as mucus production, can constrain non-pathogenic strains. Some O157:H7 initially co-localized with cellular actin. Loss of actin and epithelial integrity was observed after 4 hours. O157:H7 grew as filaments, consistent with activation of the bacterial SOS stress response. SOS is induced by reactive oxygen species (ROS), and O157:H7 infection increased ROS production. Transcriptional profiling (RNAseq) demonstrated that both commensal and O157:H7 upregulated genes associated with gastrointestinal maturation, while infection with O157:H7 upregulated inflammatory responses, including interleukin 8 (IL-8). IL-8 is associated with neutrophil recruitment, and infection with O157:H7 resulted in recruitment of human neutrophils into the iHIO tissue.

  10. Glycolipid-peptide conjugate vaccines enhance CD8+ T cell responses against human viral proteins.

    Science.gov (United States)

    Speir, M; Authier-Hall, A; Brooks, C R; Farrand, K J; Compton, B J; Anderson, R J; Heiser, A; Osmond, T L; Tang, C W; Berzofsky, J A; Terabe, M; Painter, G F; Hermans, I F; Weinkove, R

    2017-10-27

    An important goal of vaccination against viruses and virus-driven cancers is to elicit cytotoxic CD8+ T cells specific for virus-derived peptides. CD8+ T cell responses can be enhanced by engaging help from natural killer T (NKT) cells. We have produced synthetic vaccines that induce strong peptide-specific CD8+ T cell responses in vivo by incorporating an NKT cell-activating glycolipid. Here we examine the effect of a glycolipid-peptide conjugate vaccine incorporating an NKT cell-activating glycolipid linked to an MHC class I-restricted peptide from a viral antigen in human peripheral blood mononuclear cells. The vaccine induces CD1d-dependent activation of human NKT cells following enzymatic cleavage, activates human dendritic cells in an NKT-cell dependent manner, and generates a pool of activated antigen-specific CD8+ T cells with cytotoxic potential. Compared to unconjugated peptide, the vaccine upregulates expression of genes encoding interferon-γ, CD137 and granzyme B. A similar vaccine incorporating a peptide from the clinically-relevant human papilloma virus (HPV) 16 E7 oncoprotein induces cytotoxicity against peptide-expressing targets in vivo, and elicits a better antitumor response in a model of E7-expressing lung cancer than its unconjugated components. Glycolipid-peptide conjugate vaccines may prove useful for the prevention or treatment of viral infections and tumors that express viral antigens.

  11. Orienting asymmetries in dogs' responses to different communicatory components of human speech.

    Science.gov (United States)

    Ratcliffe, Victoria F; Reby, David

    2014-12-15

    It is well established that in human speech perception the left hemisphere (LH) of the brain is specialized for processing intelligible phonemic (segmental) content (e.g., [1-3]), whereas the right hemisphere (RH) is more sensitive to prosodic (suprasegmental) cues. Despite evidence that a range of mammal species show LH specialization when processing conspecific vocalizations, the presence of hemispheric biases in domesticated animals' responses to the communicative components of human speech has never been investigated. Human speech is familiar and relevant to domestic dogs (Canis familiaris), who are known to perceive both segmental phonemic cues and suprasegmental speaker-related and emotional prosodic cues. Using the head-orienting paradigm, we presented dogs with manipulated speech and tones differing in segmental or suprasegmental content and recorded their orienting responses. We found that dogs showed a significant LH bias when presented with a familiar spoken command in which the salience of meaningful phonemic (segmental) cues was artificially increased but a significant RH bias in response to commands in which the salience of intonational or speaker-related (suprasegmental) vocal cues was increased. Our results provide insights into mechanisms of interspecific vocal perception in a domesticated mammal and suggest that dogs may share ancestral or convergent hemispheric specializations for processing the different functional communicative components of speech with human listeners. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Adaptive allocation of decisionmaking responsibility between human and computer in multitask situations

    Science.gov (United States)

    Chu, Y.-Y.; Rouse, W. B.

    1979-01-01

    As human and computer come to have overlapping decisionmaking abilities, a dynamic or adaptive allocation of responsibilities may be the best mode of human-computer interaction. It is suggested that the computer serve as a backup decisionmaker, accepting responsibility when human workload becomes excessive and relinquishing responsibility when workload becomes acceptable. A queueing theory formulation of multitask decisionmaking is used and a threshold policy for turning the computer on/off is proposed. This policy minimizes event-waiting cost subject to human workload constraints. An experiment was conducted with a balanced design of several subject runs within a computer-aided multitask flight management situation with different task demand levels. It was found that computer aiding enhanced subsystem performance as well as subjective ratings. The queueing model appears to be an adequate representation of the multitask decisionmaking situation, and to be capable of predicting system performance in terms of average waiting time and server occupancy. Server occupancy was further found to correlate highly with the subjective effort ratings.

  13. Review of evoked and event-related delta responses in the human brain.

    Science.gov (United States)

    Güntekin, Bahar; Başar, Erol

    2016-05-01

    In the last decade, the brain's oscillatory responses have invaded the literature. The studies on delta (0.5-3.5Hz) oscillatory responses in humans upon application of cognitive paradigms showed that delta oscillations are related to cognitive processes, mainly in decision making and attentional processes. The present manuscript comprehensively reviews the studies on delta oscillatory responses upon cognitive stimulation in healthy subjects and in different pathologies, namely Alzheimer's disease, Mild Cognitive Impairment (MCI), bipolar disorder, schizophrenia and alcoholism. Further delta oscillatory response upon presentation of faces, facial expressions, and affective pictures are reviewed. The relationship between pre-stimulus delta activity and post-stimulus evoked and event-related responses and/or oscillations is discussed. Cross-frequency couplings of delta oscillations with higher frequency windows are also included in the review. The conclusion of this review includes several important remarks, including that delta oscillatory responses are involved in cognitive and emotional processes. A decrease of delta oscillatory responses could be a general electrophysiological marker for cognitive dysfunction (Alzheimer's disease, MCI, bipolar disorder, schizophrenia and alcoholism). The pre-stimulus activity (phase or amplitude changes in delta activity) has an effect on post-stimulus EEG responses. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Human T-cell responses to the glucosyltransferases of Streptococcus mutans.

    Science.gov (United States)

    Chia, J S; You, C M; Hu, C Y; Chiang, B L; Chen, J Y

    2001-03-01

    We previously reported differential humoral responses to glucosyltransferases (GTFs), with significantly higher saliva and serum antibody levels to GtfD than to GtfB or GtfC. To test the hypothesis that cellular immune responses to these molecules also may differ, peripheral blood mononuclear cell (PBMC) and T-cell proliferative responses in young adults and children with distinct genetic backgrounds were determined using purified recombinant GtfC and GtfD. PBMCs from all of the volunteers responded to GtfC and -D, but responses were directed predominantly towards GtfD and were major histocompatibility class II antigen dependent. A predominant T-cell response to GtfD, over GtfC, was detectable at various antigen concentrations ranging from 1 to 20 microg/ml and correlated with the differential serum immunoglobulin G (IgG) and salivary IgA antibody responses to the GTFs. Therefore, in naturally sensitized humans, Streptococcus mutans GTFs stimulate differential humoral and cellular immune responses, with the secreted form of GtfD eliciting a stronger response than the cell wall-associated form of GtfC.

  15. Perceptual and neural responses to sweet taste in humans and rodents.

    Science.gov (United States)

    Lemon, Christian H

    2015-08-01

    This mini-review discusses some of the parallels between rodent neurophysiological and human psychophysical data concerning temperature effects on sweet taste. "Sweet" is an innately rewarding taste sensation that is associated in part with foods that contain calories in the form of sugars. Humans and other mammals can show unconditioned preference for select sweet stimuli. Such preference is poised to influence diet selection and, in turn, nutritional status, which underscores the importance of delineating the physiological mechanisms for sweet taste with respect to their influence on human health. Advances in our knowledge of the biology of sweet taste in humans have arisen in part through studies on mechanisms of gustatory processing in rodent models. Along this line, recent work has revealed there are operational parallels in neural systems for sweet taste between mice and humans, as indexed by similarities in the effects of temperature on central neurophysiological and psychophysical responses to sucrose in these species. Such association strengthens the postulate that rodents can serve as effective models of particular mechanisms of appetitive taste processing. Data supporting this link are discussed here, as are rodent and human data that shed light on relationships between mechanisms for sweet taste and ingestive disorders, such as alcohol abuse. Rodent models have utility for understanding mechanisms of taste processing that may pertain to human flavor perception. Importantly, there are limitations to generalizing data from rodents, albeit parallels across species do exist.

  16. Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays

    Directory of Open Access Journals (Sweden)

    Y. Lusiyanti

    2013-12-01

    Full Text Available Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + αD + βD2. The result showed that α and β values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validated.

  17. Molecular signatures of antibody responses derived from a systems biology study of five human vaccines.

    Science.gov (United States)

    Li, Shuzhao; Rouphael, Nadine; Duraisingham, Sai; Romero-Steiner, Sandra; Presnell, Scott; Davis, Carl; Schmidt, Daniel S; Johnson, Scott E; Milton, Andrea; Rajam, Gowrisankar; Kasturi, Sudhir; Carlone, George M; Quinn, Charlie; Chaussabel, Damien; Palucka, A Karolina; Mulligan, Mark J; Ahmed, Rafi; Stephens, David S; Nakaya, Helder I; Pulendran, Bali

    2014-02-01

    Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus. To achieve this, we did a large-scale network integration of publicly available human blood transcriptomes and systems-scale databases in specific biological contexts and deduced a set of transcription modules in blood. Those modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines, which provided key insights into primary viral, protein recall and anti-polysaccharide responses. Our results elucidate the early transcriptional programs that orchestrate vaccine immunity in humans and demonstrate the power of integrative network modeling.

  18. Norovirus-specific memory T cell responses in adult human donors

    Directory of Open Access Journals (Sweden)

    Maria Malm

    2016-10-01

    Full Text Available Norovirus (NoV is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV specific serum antibodies which block the binding of NoV virus-like particles (VLPs to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney, and GI.3, and IFN-g production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539 amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-g in response to the peptides and five subjects produced IFN-g in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151 was identified in two subjects, both having human leukocyte antigen (HLA-A*02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.

  19. [Neurobiological determinism: questionable inferences on human freedom of choice and forensic criminal responsibility].

    Science.gov (United States)

    Urbaniok, F; Hardegger, J; Rossegger, A; Endrass, J

    2006-08-01

    Several authors argue that criminal behavior is generally caused by neurobiological deficits. Based on this neurobiological perspective of assumed causality, the concept of free will is questioned, and the theory of neurobiological determinism of all human behavior is put forward, thus maintaining that human beings are not responsible for their actions, and consequently the principle of guilt should be given up in criminal law. In this context the controversial debate on determinism and indeterminism, which has been held for centuries, has flared up anew, especially within the science of criminal law. When critically examining the current state of research, it becomes apparent that the results do not support the existence of a universally valid neurobiological causality of criminal behavior, nor a theory of an absolute neurobiological determinism. Neither is complete determination of all phenomena in the universe--as maintained--the logical conclusion of the principle of causality, nor is it empirically confirmed. Analyzed methodically, it cannot be falsified, and thus, as a theory which cannot be empirically tested, it represents a dogma against which plausible objections can be made. The criticism of the concept of free will, and even more so of human accountability and criminal responsibility, is not put forward in a valid way. The principle of relative determinism--the evaluation of the degree of determinism of personality factors potentially reducing criminal responsibility, which includes concrete observations and analysis of behavior--thus remains a central and cogent approach to the assessment of criminal responsibility. To sum up, the theories proposed by some authors on the complete neurobiological determinism of human behavior, and the subsequent impossibility of individual responsibility and guilt, reveal both methodical misconception and a lack of empirical foundation.

  20. Human Novelty Response to Emotional Animal Vocalizations: Effects of Phylogeny and Familiarity

    Directory of Open Access Journals (Sweden)

    Marina Scheumann

    2017-10-01

    Full Text Available Darwin (1872 postulated that emotional expressions contain universals that are retained across species. We recently showed that human rating responses were strongly affected by a listener's familiarity with vocalization types, whereas evidence for universal cross-taxa emotion recognition was limited. To disentangle the impact of evolutionarily retained mechanisms (phylogeny and experience-driven cognitive processes (familiarity, we compared the temporal unfolding of event-related potentials (ERPs in response to agonistic and affiliative vocalizations expressed by humans and three animal species. Using an auditory oddball novelty paradigm, ERPs were recorded in response to task-irrelevant novel sounds, comprising vocalizations varying in their degree of phylogenetic relationship and familiarity to humans. Vocalizations were recorded in affiliative and agonistic contexts. Offline, participants rated the vocalizations for valence, arousal, and familiarity. Correlation analyses revealed a significant correlation between a posteriorly distributed early negativity and arousal ratings. More specifically, a contextual category effect of this negativity was observed for human infant and chimpanzee vocalizations but absent for other species vocalizations. Further, a significant correlation between the later and more posteriorly P3a and P3b responses and familiarity ratings indicates a link between familiarity and attentional processing. A contextual category effect of the P3b was observed for the less familiar chimpanzee and tree shrew vocalizations. Taken together, these findings suggest that early negative ERP responses to agonistic and affiliative vocalizations may be influenced by evolutionary retained mechanisms, whereas the later orienting of attention (positive ERPs may mainly be modulated by the prior experience.

  1. Species-specific responses of Late Quaternary megafauna to climate and humans

    Science.gov (United States)

    Lorenzen, Eline D.; Nogués-Bravo, David; Orlando, Ludovic; Weinstock, Jaco; Binladen, Jonas; Marske, Katharine A.; Ugan, Andrew; Borregaard, Michael K.; Gilbert, M. Thomas P.; Nielsen, Rasmus; Ho, Simon Y. W.; Goebel, Ted; Graf, Kelly E.; Byers, David; Stenderup, Jesper T.; Rasmussen, Morten; Campos, Paula F.; Leonard, Jennifer A.; Koepfli, Klaus-Peter; Froese, Duane; Zazula, Grant; Stafford, Thomas W.; Aaris-Sørensen, Kim; Batra, Persaram; Haywood, Alan M.; Singarayer, Joy S.; Valdes, Paul J.; Boeskorov, Gennady; Burns, James A.; Davydov, Sergey P.; Haile, James; Jenkins, Dennis L.; Kosintsev, Pavel; Kuznetsova, Tatyana; Lai, Xulong; Martin, Larry D.; McDonald, H. Gregory; Mol, Dick; Meldgaard, Morten; Munch, Kasper; Stephan, Elisabeth; Sablin, Mikhail; Sommer, Robert S.; Sipko, Taras; Scott, Eric; Suchard, Marc A.; Tikhonov, Alexei; Willerslev, Rane; Wayne, Robert K.; Cooper, Alan; Hofreiter, Michael; Sher, Andrei; Shapiro, Beth; Rahbek, Carsten; Willerslev, Eske

    2014-01-01

    Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary remain contentious. We use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, underscoring the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change. PMID:22048313

  2. Ownership and human tissue - the legal conundrum: A response to Jordaan's critique.

    Science.gov (United States)

    Mahomed, S; Nöthling-Slabbert, M; Pepper, M S

    2017-02-27

    The debate over whether there should be a property or non-property approach with regard to human tissue is only the tip of the iceberg, because the issues involved are very complex, reflecting profound considerations on the nature of the self and the structuring of society; the balance of power between the citizen, the government and commercial interests; and human beings' perceptions of themselves and their bodies. This article responds to a publication by Donrich Jordaan titled 'Social justice and research using human biological material: A response to Mahomed, Nöthling-Slabbert and Pepper' in the July 2016 SAMJ. The original article to which Jordaan's critique refers and that provides the source for his response appeared in the South African Journal of Bioethics and Law in 2013, titled 'The legal position on the classification of human tissue in South Africa: Can tissues be owned?'. It is our contention that Jordaan's critique is based on a misinterpretation of the issues raised relating to the ownership of human tissue, an issue extensively debated in the academic sphere for many years. Jordaan's critique focuses on selected aspects of the original article and draws unjustifiable inferences from these. The purpose of this article is to contextualise Jordaan's critique and reaffirm the validity of the arguments made in the original article in 2013. There are, however, certain aspects of Jordaan's critique that we as authors of the original article acknowledge and appreciate in the spirit of academic discourse.

  3. Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure

    Science.gov (United States)

    Mesaros, Clementina; Worth, Andrew J; Snyder, Nathaniel W; Christofidou-Solomidou, Melpo; Vachani, Anil; Albelda, Steven M; Blair, Ian A

    2015-01-01

    Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses. PMID:26039812

  4. Ebolaviruses Associated with Differential Pathogenicity Induce Distinct Host Responses in Human Macrophages.

    Science.gov (United States)

    Olejnik, Judith; Forero, Adriana; Deflubé, Laure R; Hume, Adam J; Manhart, Whitney A; Nishida, Andrew; Marzi, Andrea; Katze, Michael G; Ebihara, Hideki; Rasmussen, Angela L; Mühlberger, Elke

    2017-06-01

    Ebola virus (EBOV) and Reston virus (RESTV) are members of the Ebolavirus genus which greatly differ in their pathogenicity. While EBOV causes a severe disease in humans characterized by a dysregulated inflammatory response and elevated cytokine and chemokine production, there are no reported disease-associated human cases of RESTV infection, suggesting that RESTV is nonpathogenic for humans. The underlying mechanisms determining the pathogenicity of different ebolavirus species are not yet known. In this study, we dissected the host response to EBOV and RESTV infection in primary human monocyte-derived macrophages (MDMs). As expected, EBOV infection led to a profound proinflammatory response, including strong induction of type I and type III interferons (IFNs). In contrast, RESTV-infected macrophages remained surprisingly silent. Early activation of IFN regulatory factor 3 (IRF3) and NF-κB was observed in EBOV-infected, but not in RESTV-infected, MDMs. In concordance with previous results, MDMs treated with inactivated EBOV and Ebola virus-like particles (VLPs) induced NF-κB activation mediated by Toll-like receptor 4 (TLR4) in a glycoprotein (GP)-dependent manner. This was not the case in cells exposed to live RESTV, inactivated RESTV, or VLPs containing RESTV GP, indicating that RESTV GP does not trigger TLR4 signaling. Our results suggest that the lack of immune activation in RESTV-infected MDMs contributes to lower pathogenicity by preventing the cytokine storm observed in EBOV infection. We further demonstrate that inhibition of TLR4 signaling abolishes EBOV GP-mediated NF-κB activation. This finding indicates that limiting the excessive TLR4-mediated proinflammatory response in EBOV infection should be considered as a potential supportive treatment option for EBOV disease.IMPORTANCE Emerging infectious diseases are a major public health concern, as exemplified by the recent devastating Ebola virus (EBOV) outbreak. Different ebolavirus species are

  5. Biomechanical response of the human body inside a military vehicle exposed to mine explosion

    OpenAIRE

    Lee, KyuSang

    1998-01-01

    Biomechanical response of the human body inside a military vehicle exposed to AP mine explosion was studied using the finite element method. The main focus was placed on evaluation of the injury potential of the human body, particularly the brain, neck (cervical spine), and legs. Injury criteria used to evaluate the injury potential were HIC, IARV's, and some others. The military vehicle used in this research was M 1097A2, the basic model of HUMVEE. In addition to the evaluation of the injury...

  6. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

    Directory of Open Access Journals (Sweden)

    Xu Dong

    2010-02-01

    Full Text Available Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions.An agent-based modeling (ABM framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (noninfectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades.The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would

  7. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

    Science.gov (United States)

    Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

    2010-02-18

    Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve

  8. The genomic analysis of lactic acidosis and acidosis response in human cancers.

    Directory of Open Access Journals (Sweden)

    Julia Ling-Yu Chen

    2008-12-01

    Full Text Available The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This "inhibition of glycolysis" phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.

  9. Identification of enzymes responsible for nitrazepam metabolism and toxicity in human.

    Science.gov (United States)

    Konishi, Keigo; Fukami, Tatsuki; Gotoh, Saki; Nakajima, Miki

    2017-09-15

    Nitrazepam (NZP) is a hypnotic agent that rarely causes liver injuries in humans and teratogenicity in rodents. In humans, NZP is primarily metabolized to 7-aminonitrazepam (ANZP) by reduction and subsequently to 7-acetylamino nitrazepam (AANZP) by acetylation. ANZP can be regenerated from AANZP by hydrolysis in rodents, but it is still unclear whether this reaction occurs in humans. In rodents, AANZP may be associated with teratogenicity, while in humans, it is known that drug-induced liver injuries may be caused by NZP reactive metabolite(s). In this study, we attempted to identify the enzymes responsible for NZP metabolism to obtain a basic understanding of this process and the associated metabolite toxicities. We found that the NZP reductase activity in human liver cytosol (HLC) was higher than that in human liver microsomes (HLM). We purified the responsible enzyme(s) from HLC and found that the NZP reductase was aldehyde oxidase 1 (AOX1). The role of AOX1 was confirmed by an observed increase in the NZP reductase activity upon addition of N1-methylnicotinamide, an electron donor of AOX1, as well as inhibition of this activity in HLC in the presence of AOX1 inhibitors. ANZP was acetylated to form AANZP by N-acetyltransferase (NAT) 2. An experiment using recombinant esterases in an inhibition study using HLM revealed that AANZP is hydrolyzed by arylacetamide deacetylase (AADAC) in the human liver. N-Hydroxylamino NZP, which is suspected to be a reactive metabolite, was detected as a conjugate with N-acetyl-l-cysteine through NZP reduction and ANZP hydroxylation reactions. In the latter reaction, the conjugate was readily formed by recombinant CYP3A4 among the various P450 isoforms tested. In sum, we found that AOX1, NAT2, AADAC, and CYP3A4 are the determinants for the pharmacokinetics of NZP and that they confer interindividual variability in sensitivity to NZP side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

    Science.gov (United States)

    Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC. PMID:22291031

  11. HCV-induced immune responses influence the development of operational tolerance after liver transplantation in humans.

    Science.gov (United States)

    Bohne, Felix; Londoño, María-Carlota; Benítez, Carlos; Miquel, Rosa; Martínez-Llordella, Marc; Russo, Carolina; Ortiz, Cecilia; Bonaccorsi-Riani, Eliano; Brander, Christian; Bauer, Tanja; Protzer, Ulrike; Jaeckel, Elmar; Taubert, Richard; Forns, Xavier; Navasa, Miquel; Berenguer, Marina; Rimola, Antoni; Lozano, Juan-José; Sánchez-Fueyo, Alberto

    2014-06-25

    Pathogen-induced immune responses prevent the establishment of transplantation tolerance in experimental animal models. Whether this occurs in humans as well remains unclear. The development of operational tolerance in liver transplant recipients with chronic hepatitis C virus (HCV) infection allows us to address this question. We conducted a clinical trial of immunosuppression withdrawal in HCV-infected adult liver recipients to elucidate (i) the mechanisms through which allograft tolerance can be established in the presence of an ongoing inflammatory response and (ii) whether anti-HCV heterologous immune responses influence this phenomenon. Of 34 enrolled liver recipients, drug withdrawal was successful in 17 patients (50%). Tolerance was associated with intrahepatic overexpression of type I interferon and immunoregulatory genes and with an expansion of exhausted PD1/CTLA4/2B4-positive HCV-specific circulating CD8(+) T cells. These findings were already present before immunosuppression was discontinued and were specific for HCV infection. In contrast, the magnitude of HCV-induced proinflammatory gene expression and the breadth of anti-HCV effector T cell responses did not influence drug withdrawal outcome. Our data suggest that in humans, persistent viral infections exert immunoregulatory effects that could contribute to the restraining of alloimmune responses, and do not necessarily preclude the development of allograft tolerance. Copyright © 2014, American Association for the Advancement of Science.

  12. Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages.

    Directory of Open Access Journals (Sweden)

    Henrik Andersson

    Full Text Available Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response contributing to the early control of Mtb infection.

  13. Nystagmus responses in a group of normal humans during earth-horizontal axis rotation

    Science.gov (United States)

    Wall, Conrad, III; Furman, Joseph M. R.

    1989-01-01

    Horizontal eye movement responses to earth-horizontal yaw axis rotation were evaluated in 50 normal human subjects who were uniformly distributed in age (20-69 years) and each age group was then divided by gender. Subjects were rotated with eyes open in the dark, using clockwise and counter-clockwise 60 deg velocity trapezoids. The nystagmus slow component velocity is analyzed. It is shown that, despite large intersubject variability, parameters which describe earth-horizontal yaw axis responses are loosely interrelated, and some of them vary significantly with gender and age.

  14. Influence of ventilation and hypocapnia on sympathetic nerve responses to hypoxia in normal humans.

    Science.gov (United States)

    Somers, V K; Mark, A L; Zavala, D C; Abboud, F M

    1989-11-01

    The sympathetic response to hypoxia depends on the interaction between chemoreceptor stimulation (CRS) and the associated hyperventilation. We studied this interaction by measuring sympathetic nerve activity (SNA) to muscle in 13 normal subjects, while breathing room air, 14% O2, 10% O2, and 10% O2 with added CO2 to maintain isocapnia. Minute ventilation (VE) and blood pressure (BP) increased significantly more during isocapnic hypoxia (IHO) than hypocapnic hypoxia (HHO). In contrast, SNA increased more during HHO [40 +/- 10% (SE)] than during IHO (25 +/- 19%, P less than 0.05). To determine the reason for the lesser increase in SNA with IHO, 11 subjects underwent voluntary apnea during HHO and IHO. Apnea potentiated the SNA responses to IHO more than to HHO. SNA responses to IHO were 17 +/- 7% during breathing and 173 +/- 47% during apnea whereas SNA responses to HHO were 35 +/- 8% during breathing and 126 +/- 28% during apnea. During ventilation, the sympathoexcitation of IHO (compared with HHO) is suppressed, possibly for two reasons: 1) because of the inhibitory influence of activation of pulmonary afferents as a result of a greater increase in VE, and 2) because of the inhibitory influence of baroreceptor activation due to a greater rise in BP. Thus in humans, the ventilatory response to chemoreceptor stimulation predominates and restrains the sympathetic response. The SNA response to chemoreceptor stimulation represents the net effect of the excitatory influence of the chemoreflex and the inhibitory influence of pulmonary afferents and baroreceptor afferents.

  15. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus.

    Directory of Open Access Journals (Sweden)

    Cyril Le Nouën

    2011-06-01

    Full Text Available Human respiratory syncytial virus (HRSV and, to a lesser extent, human metapneumovirus (HMPV and human parainfluenza virus type 3 (HPIV3, can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV-stimulated DC to

  16. Plantar flexor stretch reflex responses to whole body loading/unloading during human walking

    DEFF Research Database (Denmark)

    Grey, Michael James; van Doornik, Johannes; Sinkjær, Thomas

    2002-01-01

    perturbation during human walking. Three body load conditions were investigated: normal body load, a 30% increase in body load, and a 30% decrease in body load. Healthy subjects walked on a treadmill at approximately 3.6 km/h with the left ankle attached to a portable stretching device. Dorsiflexion......Numerous animal and human studies have shown that afferent information from the periphery contributes to the control of walking. In particular, recent studies have consistently shown that load receptor input is an important element of the locomotion control mechanism. The objective of this study...... electrodes. Stretch reflex responses were observed in the soleus and gastrocnemius muscles for all of the body load conditions; however, increasing or decreasing the body load did not affect the timing and magnitude of the responses. This study provides evidence that load receptor input does not contribute...

  17. Simplified data access on human skeletal muscle transcriptome responses to differentiated exercise

    DEFF Research Database (Denmark)

    Vissing, Kristian; Schjerling, Peter

    2014-01-01

    and interpret by individuals that are inexperienced with bioinformatics procedures. In a comparative study, we therefore; (1) investigated the human skeletal muscle transcriptome responses to differentiated exercise and non-exercise control intervention, and; (2) set out to develop a straightforward search tool......Few studies have investigated exercise-induced global gene expression responses in human skeletal muscle and these have typically focused at one specific mode of exercise and not implemented non-exercise control models. However, interpretation on effects of differentiated exercise necessitate...... direct comparison between essentially different modes of exercise and the ability to identify true exercise effect, necessitate implementation of independent non-exercise control subjects. Furthermore, muscle transcriptome data made available through previous exercise studies can be difficult to extract...

  18. Species-specific responses of Late Quaternary megafauna to climate and humans

    DEFF Research Database (Denmark)

    Lorenzen, Eline D; Nogués-Bravo, David; Orlando, Ludovic

    2011-01-01

    the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human...... encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic...... signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change....

  19. Distal promoter regions are responsible for differential regulation of human orosomucoid-1 and -2 gene expression and acute phase responses.

    Science.gov (United States)

    Sai, Kimie; Kurose, Kouichi; Koizumi, Tomoko; Katori, Noriko; Sawada, Jun-ichi; Matsumura, Yasuhiro; Saijo, Nagahiro; Yamamoto, Noboru; Tamura, Tomohide; Okuda, Haruhiro; Saito, Yoshiro

    2014-01-01

    Human orosomucoid (ORM) is a major acute-phase plasma protein, encoded by 2 highly homologous genes, ORM1 and ORM2. Human ORM induction is assumed to be regulated by each proximal promoter region, where putative glucocorticoid responsive elements and CCAAT/enhancer binding protein (C/EBP)β binding sites are located. However, the details of the differential regulation of these genes remain unknown. To explore this, we assessed the role of the distal promoter region of each ORM in HeLa cells. Luciferase-reporter activities of full constructs, containing approximately 1.1 kbp (FULL), and those of deletion constructs, containing up to 188 bp region (DEL) upstream of the transcription start sites of ORM1 and ORM2 were compared under both basal and inducer-treated conditions. For ORM1 and ORM2 DEL constructs, significantly increased activities after dexamethasone (DEX) treatments (alone and combined with interleukin (IL)-1β) were observed. Significantly higher FULL construct activities than DEL construct activities were observed for ORM1 after IL-1β treatment, while those for ORM2 were significantly lower at basal level and after DEX treatments. Upon C/EBPβ overexpression, FULL construct activities were significantly higher than those of DEL constructs at basal level and after IL-1β treatment for ORM1, and at basal level and after inducer-treatments for ORM2. Higher transcription-induction activity in the distal promoter region was evident for ORM1 in the absence of C/EBPβ overexpression, and for ORM2 under C/EBPβ overexpression conditions. These findings suggest that the ORM distal promoter region differentially regulates expression of ORM genes at basal level and in acute phase responses.

  20. Optimal Fluxes, Reaction Replaceability, and Response to Enzymopathies in the Human Red Blood Cell

    OpenAIRE

    De Martino, A.; Granata, D.; Marinari, E; Martelli, C.; Van Kerrebroeck, V.

    2010-01-01

    Characterizing the capabilities, key dependencies, and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful reaction knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cel...

  1. Human Plasmacytoid Dendritic Cells Elicited Different Responses after Infection with Pathogenic and Nonpathogenic Junin Virus Strains

    OpenAIRE

    Negrotto, Soledad; Mena, Hebe A.; Ure, Agustin E.; Jaquenod De Giusti, Carolina; Bollati-Fogolín, Mariela; Vermeulen, Elba M.; Schattner, Mirta; Gómez, Ricardo M.

    2015-01-01

    The arenavirus Junin virus (JUNV) is the etiologic agent of Argentine hemorrhagic fever. We characterized the JUNV infection of human peripheral blood-derived plasmacytoid dendritic cells (hpDC), demonstrating that hpDC are susceptible to infection with the C#1 strain (attenuated) and even more susceptible to infection with the P (virulent) JUNV strain. However, hpDC elicited different responses in terms of viability, activation, maturation, and cytokine expression after infection with both J...

  2. Negatively-charged air conditions and responses of the human psycho-neuro-endocrino-immune network.

    Science.gov (United States)

    Takahashi, Kazuaki; Otsuki, Takemi; Mase, Akinori; Kawado, Takashi; Kotani, Muneo; Ami, Kazuhisa; Matsushima, Hiroki; Nishimura, Yasumitsu; Miura, Yoshie; Murakami, Shuko; Maeda, Megumi; Hayashi, Hiroaki; Kumagai, Naoko; Shirahama, Takashi; Yoshimatsu, Michiharu; Morimoto, Kanehisa

    2008-08-01

    Against increasing environmental adverse effects on human health such as those associated with water and ground pollution, as well as out- and indoor air conditions, trials were conducted to support and promote human health by improving the indoor air atmosphere. This study was performed to estimate the effect of negatively-charged air conditions on human biological markers related to the psycho-neuro-endocrino-immune (PNEI) network. After construction of negatively-charged experimental rooms (NCRs), healthy volunteers were admitted to these rooms and control rooms (CTRs) and various biological responses were analyzed. NCRs were constructed using a fine charcoal coating and applying an electric voltage (72 V) between the backside of walls and the ground. Various biological markers were monitored that related to general conditions, autonomic nervous systems, stress markers, immunological parameters and blood flow. Regarding the indoor environment, only negatively-charged air resulted in the difference between the CTR and NCR groups. The well-controlled experimental model-room to examine the biological effects of negatively-charged air was therefore established. Among the various parameters, IL-2, IL-4, the mean RR interval of the heart rate, and blood viscosity differed significantly between the CTR and NCR groups. In addition, the following formula was used to detect NCR-biological responses: Biological Response Value (BRV)=0.498+0.0005 [salivary cortisol]+0.072 [IL-2]+0.003 [HRM-SD]-0.013 [blood viscosity]-0.009 [blood sugar]+0.017 [pulse rate]. Negatively-charged air conditions activated the immune system slightly, smoothened blood flow and stabilized the autonomic nervous system. Although this is the first report to analyze negatively-charged air conditions on human biological responses, the long-term effects should be analyzed for the general use of these artificial atmospheres.

  3. Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

    Directory of Open Access Journals (Sweden)

    Cheng-Yuk Lee

    Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

  4. Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

    Science.gov (United States)

    Bai, Jianwu; Smock, Steven L; Jackson, George R; MacIsaac, Kenzie D; Huang, Yongsheng; Mankus, Courtney; Oldach, Jonathan; Roberts, Brian; Ma, Yu-Lu; Klappenbach, Joel A; Crackower, Michael A; Alves, Stephen E; Hayden, Patrick J

    2015-01-01

    Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively. ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3), and novel ones that were identified for the first time in this study (e.g. CCRL1). ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.

  5. Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

    Directory of Open Access Journals (Sweden)

    Jianwu Bai

    Full Text Available Human airway epithelial cells are the principal target of human rhinovirus (HRV, a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1 to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2 to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model.Air-liquid interface (ALI human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively.ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3, and novel ones that were identified for the first time in this study (e.g. CCRL1.ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.

  6. Animal models and their importance to human physiological responses in microgravity

    Science.gov (United States)

    Tipton, C. M.

    1996-01-01

    Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

  7. From responsible robotics towards a human rights regime oriented to the challenges of robotics and artificial intelligence

    DEFF Research Database (Denmark)

    Liu, Hin-Yan; Zawieska, Karolina

    2017-01-01

    impulse by proposing a complementary set of human rights directed specifically against the harms arising from robotic and artificial intelligence (AI) technologies. The relationship between responsibilities of the agent and the rights of the patient suggest that a rights regime is the other side...... to act responsibly. This subsists within a larger phenomenon where the difference between humans and non-humans, be it animals or artificial systems, appears to be increasingly blurred, thereby disrupting orthodox understandings of responsibility. This paper seeks to supplement the responsible robotics...

  8. Identification and Characterization of Cyclic AMP Response Element-Binding Protein H Response Element in the Human Apolipoprotein A5 Gene Promoter

    Directory of Open Access Journals (Sweden)

    Kwang Hoon Song

    2013-01-01

    Full Text Available The cyclic AMP response element-binding protein H (CREBH plays important roles in hepatic lipogenesis, fatty acid oxidation, and lipolysis under metabolic stress. Here, we report CREBH as a novel regulator of human APOA5. Knockdown of endogenous CREBH expression via small interfering RNA resulted in the downregulation of human APOA5 mRNA expression in human hepatoma cells, HepG2. Sequence analysis suggested that putative CREBH response element (CREBHRE is located in the human APOA5 promoter region and is highly conserved in both human and rodent. To clarify whether the human APOA5 promoter is regulated by CREBH, we analyzed the human APOA5 promoter region using a transient transfection assay and determined that transfection of CREBH induced human APOA5 promoter activity. Moreover, it was shown that CREBH directly regulated human APOA5 gene expression by binding to a unique CREBHRE located in the proximal human APOA5 promoter region, using 5′-deletion and mutagenesis of human APOA5 promoter analysis and chromatin immunoprecipitation assay. Taken together, our results demonstrated that human APOA5 is directly regulated by CREBH via CREBHRE and provided a new insight into the role of this liver-specific bZIP transcription factor in lipoprotein metabolism and triglyceride homeostasis.

  9. Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.

    Directory of Open Access Journals (Sweden)

    Anne C Teirlinck

    2011-12-01

    Full Text Available Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz and asexual blood-stage (PfRBC malaria parasites in naïve human volunteers undergoing single (n = 5 or multiple (n = 10 experimental P. falciparum infections under highly controlled conditions. IFNγ and interleukin-2 (IL-2 responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only 'adaptive' but also 'innate' lymphocyte subsets contribute to the increased IFNγ response, including αβT cells, γδT cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the αβT cells and γδT compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO(+ CD62L(- effector memory (EM phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFNγ(+IL-2(+ EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P

  10. Genetic selection for modulators of a retinoic-acid-responsive reporter in human cells.

    Science.gov (United States)

    Richards, Burt; Karpilow, Jon; Dunn, Christine; Peterson, Isaac; Maxfield, Andrew; Zharkikh, Ludmilla; Abedi, Majid; Hurlburt, Anthony; Hardman, Joshua; Hsu, Forrest; Li, Wenhua; Rebentisch, Matthew; Sandrock, Robert; Sandrock, Tanya; Kamb, Alexander; Teng, David H-F

    2003-03-01

    We used a genetic screening methodology, a human cell line bearing a retinoic-acid-responsive enhanced GFP reporter, and a flow sorter to recover dominant modulators of reporter expression. Four inducers and three suppressors that were fused to the C terminus of a protein scaffold for stability were isolated and their mechanisms of action studied. Mutagenesis experiments indicated that six of these dominant agents exerted their effects at the protein level. The single cDNA coding fragment that was isolated comprised the central 64-amino-acid section of human cyclophilin B, which contained its peptidyl-prolyl isomerase domain; this cyclophilin fragment repressed expression of the retinoic-acid-responsive reporter. The remaining clones encoded peptides shorter than 30 amino acids unrelated to known gene open reading frames. Genetic epistasis studies between the strongest inducer, R3, and a dominant-negative mutant of RARalpha suggest that the two factors function in the same pathway. Transcript microarray analyses suggest that R3 induced a subset of the retinoid-responsive genes in melanoma cells. Finally, yeast two-hybrid assays and co-immunoprecipitation studies of human cell extracts identified PAT1 as a protein that interacts with R3.

  11. RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses

    Science.gov (United States)

    Akirav, Eitan M.; Preston-Hurlburt, Paula; Garyu, Justin; Henegariu, Octavian; Clynes, Raphael; Schmidt, Ann Marie; Herold, Kevan C.

    2012-01-01

    The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE− cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses. PMID:22509345

  12. Mapping the central neurocircuitry that integrates the cardiovascular response to exercise in humans.

    Science.gov (United States)

    Basnayake, Shanika D; Green, Alexander L; Paterson, David J

    2012-01-01

    There are abundant animal data attempting to identify the neural circuitry involved in cardiovascular control. Translating this research into humans has been made possible using functional neurosurgery during which deep brain stimulating electrodes are implanted into various brain nuclei for the treatment of chronic pain and movement disorders. This not only allows stimulation of the human brain, but also presents the opportunity to record neural activity from various brain regions. This symposium review highlights key experiments from the past decade that have endeavoured to identify the neurocircuitry responsible for integrating the cardiovascular response to exercise in humans. Two areas of particular interest are highlighted: the periaqueductal grey and the subthalamic nucleus. Our studies have shown that the periaqueductal grey (particularly the dorsal column) is a key part of the neurocircuitry involved in mediating autonomic changes adapted to ongoing behaviours. Emerging evidence also suggests that the subthalamic nucleus is not only involved in the control of movement, but also in the mediation of cardiovascular responses. Although these sites are unlikely to be the 'command' areas themselves, we have demonstrated that the two nuclei have the properties of being key integrating sites between the feedback signals from exercising muscle and the feedforward signals from higher cortical centres.

  13. Antibody responses in humans infected with newly emerging strains of West Nile Virus in Europe.

    Directory of Open Access Journals (Sweden)

    Stefan Chabierski

    Full Text Available Infection with West Nile Virus (WNV affects an increasing number of countries worldwide. Although most human infections result in no or mild flu-like symptoms, the elderly and those with a weakened immune system are at higher risk for developing severe neurological disease. Since its introduction into North America in 1999, WNV has spread across the continental United States and caused annual outbreaks with a total of 36,000 documented clinical cases and ∼1,500 deaths. In recent years, outbreaks of neuroinvasive disease also have been reported in Europe. The WNV strains isolated during these outbreaks differ from those in North America, as sequencing has revealed that distinct phylogenetic lineages of WNV concurrently circulate in Europe, which has potential implications for the development of vaccines, therapeutics, and diagnostic tests. Here, we studied the human antibody response to European WNV strains responsible for outbreaks in Italy and Greece in 2010, caused by lineage 1 and 2 strains, respectively. The WNV structural proteins were expressed as a series of overlapping fragments fused to a carrier-protein, and binding of IgG in sera from infected persons was analyzed. The results demonstrate that, although the humoral immune response to WNV in humans is heterogeneous, several dominant peptides are recognized.

  14. Antibody responses in humans infected with newly emerging strains of West Nile Virus in Europe.

    Science.gov (United States)

    Chabierski, Stefan; Makert, Gustavo R; Kerzhner, Alexandra; Barzon, Luisa; Fiebig, Petra; Liebert, Uwe G; Papa, Anna; Richner, Justin M; Niedrig, Matthias; Diamond, Michael S; Palù, Giorgio; Ulbert, Sebastian

    2013-01-01

    Infection with West Nile Virus (WNV) affects an increasing number of countries worldwide. Although most human infections result in no or mild flu-like symptoms, the elderly and those with a weakened immune system are at higher risk for developing severe neurological disease. Since its introduction into North America in 1999, WNV has spread across the continental United States and caused annual outbreaks with a total of 36,000 documented clinical cases and ∼1,500 deaths. In recent years, outbreaks of neuroinvasive disease also have been reported in Europe. The WNV strains isolated during these outbreaks differ from those in North America, as sequencing has revealed that distinct phylogenetic lineages of WNV concurrently circulate in Europe, which has potential implications for the development of vaccines, therapeutics, and diagnostic tests. Here, we studied the human antibody response to European WNV strains responsible for outbreaks in Italy and Greece in 2010, caused by lineage 1 and 2 strains, respectively. The WNV structural proteins were expressed as a series of overlapping fragments fused to a carrier-protein, and binding of IgG in sera from infected persons was analyzed. The results demonstrate that, although the humoral immune response to WNV in humans is heterogeneous, several dominant peptides are recognized.

  15. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

    Science.gov (United States)

    Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

    2016-01-01

    IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain

  16. Responses to the Assurance game in monkeys, apes, and humans using equivalent procedures

    DEFF Research Database (Denmark)

    Brosnan, Sarah F; Parrish, Audrey; Beran, Michael J

    2011-01-01

    from the games themselves; however, in the typical experiment, procedures and conditions differ widely, particularly between humans and other species. Thus, in the current study, we investigated how three primate species, capuchin monkeys, chimpanzees, and humans, played the Assurance (or Stag Hunt...... phylogenetic lines, which we found. However, the species were more similar than might be expected. In particular, humans who played using "nonhuman primate-friendly" rules did not behave as is typical. Thus, we find evidence for similarity in decision-making processes across the order Primates. These results......There is great interest in the evolution of economic behavior. In typical studies, species are asked to play one of a series of economic games, derived from game theory, and their responses are compared. The advantage of this approach is the relative level of consistency and control that emerges...

  17. Short-latency crossed responses in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew J T; Kamavuako, Ernest N; Geertsen, Svend Sparre

    2015-01-01

    Interlimb reflexes contribute to the central neural coordination between different limbs in both humans and animals. Although commissural interneurons have only been directly identified in animals, spinally mediated interlimb reflexes have been discovered in a number of human lower limb muscles......, indicating their existence in humans. The aim of the present study was to investigate whether short-latency crossed-spinal reflexes are present in the contralateral biceps femoris (cBF) muscle following ipsilateral knee (iKnee) joint rotations during a sitting task, where participants maintained a slight pre...... fast for a transcortical pathway to contribute. The cBF inhibitory and facilitatory reflexes followed the automatic gain control principle, with the size of the response increasing as the level of background pre-contraction in the cBF muscle increased. In addition to the surface EMG, both short...

  18. A novel human polycomb binding site acts as a functional polycomb response element in Drosophila.

    Directory of Open Access Journals (Sweden)

    Suresh Cuddapah

    Full Text Available Polycomb group (PcG proteins are key chromatin regulators implicated in multiple processes including embryonic development, tissue homeostasis, genomic imprinting, X-chromosome inactivation, and germ cell differentiation. The PcG proteins recognize target genomic loci through cis DNA sequences known as Polycomb Response Elements (PREs, which are well characterized in Drosophila. However, mammalian PREs have been elusive until two groups reported putative mammalian PREs recently. Consistent with the existence of mammalian PREs, here we report the identification and characterization of a potential PRE from human T cells. The putative human PRE has enriched binding of PcG proteins, and such binding is dependent on a key PcG component SUZ12. We demonstrate that the putative human PRE carries both genetic and molecular features of Drosophila PRE in transgenic flies, implying that not only the trans PcG proteins but also certain features of the cis PREs are conserved between mammals and Drosophila.

  19. Aggregated responses of human mobility to severe winter storms: An empirical study.

    Science.gov (United States)

    Wang, Yan; Wang, Qi; Taylor, John E

    2017-01-01

    Increasing frequency of extreme winter storms has resulted in costly damages and a disruptive impact on the northeastern United States. It is important to understand human mobility patterns during such storms for disaster preparation and relief operations. We investigated the effects of severe winter storms on human mobility during a 2015 blizzard using 2.69 million Twitter geolocations. We found that displacements of different trip distances and radii of gyration of individuals' mobility were perturbed significantly. We further explored the characteristics of perturbed mobility during the storm, and demonstrated that individuals' recurrent mobility does not have a higher degree of similarity with their perturbed mobility, when comparing with its similarity to non-perturbed mobility. These empirical findings on human mobility impacted by severe winter storms have potential long-term implications on emergency response planning and the development of strategies to improve resilience in severe winter storms.

  20. Learning of anticipatory responses in single neurons of the human medial temporal lobe.

    Science.gov (United States)

    Reddy, Leila; Poncet, Marlene; Self, Matthew W; Peters, Judith C; Douw, Linda; van Dellen, Edwin; Claus, Steven; Reijneveld, Jaap C; Baayen, Johannes C; Roelfsema, Pieter R

    2015-10-09

    Neuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL.

  1. Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

    Science.gov (United States)

    Galor, Anat; Garg, Nisha; Nanji, Afshan; Joag, Madhura; Nuovo, Gerard; Palioura, Sotiria; Wang, Gaofeng; Karp, Carol L

    2015-11-01

    To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. Retrospective case series. Twenty-seven patients with OSSN. Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. Clinical characteristics of OSSN by HPV status. Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy. Copyright © 2015 American Academy of Ophthalmology. All rights reserved.

  2. Construction of predictive promoter models on the example of antibacterial response of human epithelial cells

    Directory of Open Access Journals (Sweden)

    Wingender Edgar

    2005-01-01

    Full Text Available Abstract Background Binding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and between both cells. P. aeruginosa is a pathogen that causes acute and chronic lung infections by interacting with the pulmonary epithelial cells. We use this example for examining the ways of triggering the response of the eukaryotic cell(s, leading us to a better understanding of the details of the inflammatory process in general. Results Considering a set of genes co-expressed during the antibacterial response of human lung epithelial cells, we constructed a promoter model for the search of additional target genes potentially involved in the same cell response. The model construction is based on the consideration of pair-wise combinations of transcription factor binding sites (TFBS. It has been shown that the antibacterial response of human epithelial cells is triggered by at least two distinct pathways. We therefore supposed that there are two subsets of promoters activated by each of them. Optimally, they should be "complementary" in the sense of appearing in complementary subsets of the (+-training set. We developed the concept of complementary pairs, i.e., two mutually exclusive pairs of TFBS, each of which should be found in one of the two complementary subsets. Conclusions We suggest a simple, but exhaustive method for searching for TFBS pairs which characterize the whole (+-training set, as well as for complementary pairs. Applying this method, we came up with a promoter model of antibacterial response genes that consists of one TFBS pair which should be found in the whole training set and four complementary pairs. We applied this model to screening of 13,000 upstream regions of human genes and identified 430 new target genes which are potentially involved in antibacterial defense mechanisms.

  3. Evolutionary conservation of an atypical glucocorticoid-responsive element in the human tyrosine hydroxylase gene.

    Science.gov (United States)

    Sheela Rani, C S; Soto-Pina, Alexandra; Iacovitti, Lorraine; Strong, Randy

    2013-07-01

    The human tyrosine hydroxylase (hTH) gene has a 42 bp evolutionarily conserved region designated (CR) II at -7.24 kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7 bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines. Dexamethasone (Dex) stimulated Luc activity of hTH-CRII in HeLa cells, while mifepristone, a glucocorticoid receptor (GR) antagonist, prevented Dex stimulation. Deletion of the 7 bp 5'-TGACTAA at -7243 bp completely abolished the Dex-stimulated Luc activity of hTH-CRII construct. The AP-1 agonist, tetradeconoyl-12,13-phorbol acetate (TPA), also stimulated hTH promoter activity, and Dex and TPA together further accentuated this response. Chromatin immunoprecipitation assays revealed the presence of both GR and AP-1 proteins, especially Jun family members, at this hTH promoter site. Dex did not stimulate hTH promoter activity in a catecholaminergic cell line, which had low endogenous GR levels, but did activate the response when GR was expressed exogenously. Thus, our studies have clearly identified a glucocorticoid-responsive element in a 7 bp AP-1-like motif in the promoter region at -7.24 kb of the human TH gene. © 2013 International Society for Neurochemistry.

  4. Attributing Agency to Automated Systems: Reflections on Human-Robot Collaborations and Responsibility-Loci.

    Science.gov (United States)

    Nyholm, Sven

    2017-07-18

    Many ethicists writing about automated systems (e.g. self-driving cars and autonomous weapons systems) attribute agency to these systems. Not only that; they seemingly attribute an autonomous or independent form of agency to these machines. This leads some ethicists to worry about responsibility-gaps and retribution-gaps in cases where automated systems harm or kill human beings. In this paper, I consider what sorts of agency it makes sense to attribute to most current forms of automated systems, in particular automated cars and military robots. I argue that whereas it indeed makes sense to attribute different forms of fairly sophisticated agency to these machines, we ought not to regard them as acting on their own, independently of any human beings. Rather, the right way to understand the agency exercised by these machines is in terms of human-robot collaborations, where the humans involved initiate, supervise, and manage the agency of their robotic collaborators. This means, I argue, that there is much less room for justified worries about responsibility-gaps and retribution-gaps than many ethicists think.

  5. Specific responses of human hippocampal neurons are associated with better memory.

    Science.gov (United States)

    Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak

    2015-08-18

    A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.

  6. Minimal changes in heart rate of incubating American Oystercatchers (Haematopus palliatus) in response to human activity

    Science.gov (United States)

    Borneman, Tracy E.; Rose, Eli T.; Simons, Theodore R.

    2014-01-01

    An organism's heart rate is commonly used as an indicator of physiological stress due to environmental stimuli. We used heart rate to monitor the physiological response of American Oystercatchers (Haematopus palliatus) to human activity in their nesting environment. We placed artificial eggs with embedded microphones in 42 oystercatcher nests to record the heart rate of incubating oystercatchers continuously for up to 27 days. We used continuous video and audio recordings collected simultaneously at the nests to relate physiological response of birds (heart rate) to various types of human activity. We observed military and civilian aircraft, off-road vehicles, and pedestrians around nests. With the exception of high-speed, low-altitude military overflights, we found little evidence that oystercatcher heart rates were influenced by most types of human activity. The low-altitude flights were the only human activity to significantly increase average heart rates of incubating oystercatchers (12% above baseline). Although statistically significant, we do not consider the increase in heart rate during high-speed, low-altitude military overflights to be of biological significance. This noninvasive technique may be appropriate for other studies of stress in nesting birds.

  7. Species-Specific Responses of Carnivores to Human-Induced Landscape Changes in Central Argentina.

    Science.gov (United States)

    Caruso, Nicolás; Lucherini, Mauro; Fortin, Daniel; Casanave, Emma B

    2016-01-01

    The role that mammalian carnivores play in ecosystems can be deeply altered by human-driven habitat disturbance. While most carnivore species are negatively affected, the impact of habitat changes is expected to depend on their ecological flexibility. We aimed to identify key factors affecting the habitat use by four sympatric carnivore species in landscapes of central Argentina. Camera trapping surveys were carried out at 49 sites from 2011 to 2013. Each site was characterized by 12 habitat attributes, including human disturbance and fragmentation. Four landscape gradients were created from Principal Component Analysis and their influence on species-specific habitat use was studied using Generalized Linear Models. We recorded 74 events of Conepatus chinga, 546 of Pseudalopex gymnocercus, 193 of Leopardus geoffroyi and 45 of Puma concolor. We found that the gradient describing sites away from urban settlements and with low levels of disturbance had the strongest influence. L. geoffroyi was the only species responding significantly to the four gradients and showing a positive response to modified habitats, which could be favored by the low level of persecution by humans. P. concolor made stronger use of most preserved sites with low proportion of cropland, even though the species also used sites with an intermediate level of fragmentation. A more flexible use of space was found for C. chinga and P. gymnocercus. Our results demonstrate that the impact of human activities spans across this guild of carnivores and that species-specific responses appear to be mediated by ecological and behavioral attributes.

  8. Species-Specific Responses of Carnivores to Human-Induced Landscape Changes in Central Argentina.

    Directory of Open Access Journals (Sweden)

    Nicolás Caruso

    Full Text Available The role that mammalian carnivores play in ecosystems can be deeply altered by human-driven habitat disturbance. While most carnivore species are negatively affected, the impact of habitat changes is expected to depend on their ecological flexibility. We aimed to identify key factors affecting the habitat use by four sympatric carnivore species in landscapes of central Argentina. Camera trapping surveys were carried out at 49 sites from 2011 to 2013. Each site was characterized by 12 habitat attributes, including human disturbance and fragmentation. Four landscape gradients were created from Principal Component Analysis and their influence on species-specific habitat use was studied using Generalized Linear Models. We recorded 74 events of Conepatus chinga, 546 of Pseudalopex gymnocercus, 193 of Leopardus geoffroyi and 45 of Puma concolor. We found that the gradient describing sites away from urban settlements and with low levels of disturbance had the strongest influence. L. geoffroyi was the only species responding significantly to the four gradients and showing a positive response to modified habitats, which could be favored by the low level of persecution by humans. P. concolor made stronger use of most preserved sites with low proportion of cropland, even though the species also used sites with an intermediate level of fragmentation. A more flexible use of space was found for C. chinga and P. gymnocercus. Our results demonstrate that the impact of human activities spans across this guild of carnivores and that species-specific responses appear to be mediated by ecological and behavioral attributes.

  9. Autocrine abscisic acid mediates the UV-B-induced inflammatory response in human granulocytes and keratinocytes.

    Science.gov (United States)

    Bruzzone, Santina; Basile, Giovanna; Mannino, Elena; Sturla, Laura; Magnone, Mirko; Grozio, Alessia; Salis, Annalisa; Fresia, Chiara; Vigliarolo, Tiziana; Guida, Lucrezia; De Flora, Antonio; Tossi, Vanesa; Cassia, Raul; Lamattina, Lorenzo; Zocchi, Elena

    2012-06-01

    UV-B is an abiotic environmental stress in both plants and animals. Abscisic acid (ABA) is a phytohormone regulating fundamental physiological functions in plants, including response to abiotic stress. We previously demonstrated that ABA is an endogenous stress hormone also in animal cells. Here, we investigated whether autocrine ABA regulates the response to UV-B of human granulocytes and keratinocytes, the cells involved in UV-triggered skin inflammation. The intracellular ABA concentration increased in UV-B-exposed granulocytes and keratinocytes and ABA was released into the supernatant. The UV-B-induced production of NO and of reactive oxygen species (ROS), phagocytosis, and cell migration were strongly inhibited in granulocytes irradiated in the presence of a monoclonal antibody against ABA. Moreover, presence of the same antibody strongly inhibited release of NO, prostaglandin E2 (PGE(2)), and tumor necrosis factor-α (TNF-α) by UV-B irradiated keratinocytes. Lanthionine synthetase C-like protein 2 (LANCL2) is required for the activation of the ABA signaling pathway in human granulocytes. Silencing of LANCL2 in human keratinocytes by siRNA was accompanied by abrogation of the UV-B-triggered release of PGE(2), TNF-α, and NO and ROS production. These results indicate that UV-B irradiation induces ABA release from human granulocytes and keratinocytes and that autocrine ABA stimulates cell functions involved in skin inflammation. Copyright © 2011 Wiley Periodicals, Inc.

  10. Cow's milk challenge through human milk evokes immune responses in infants with cow's milk allergy.

    Science.gov (United States)

    Järvinen, K M; Mäkinen-Kiljunen, S; Suomalainen, H

    1999-10-01

    In order to measure the immune response evoked in breast-fed infants with cow's milk allergy (CMA) by cow's milk challenge through human milk, mothers were given increasing doses of cow's milk after they had been on a cow's milk elimination diet. Another objective was to study the secretion of beta-lactoglobulin (BLG) into human milk before and during milk challenge in relation to the appearance of symptoms in infants. Seventeen asymptomatic mothers who had infants with challenge-proven CMA and 10 asymptomatic mothers who had healthy infants were recruited. Infants ranged in age from 1.8 to 9.4 months. A solid-phase enzyme-linked immunoassay (ELISPOT) was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells. Flow cytometry was used to enumerate different lymphocyte subpopulations among peripheral blood lymphocytes primed during provocation by cow's milk antigens. BLG levels were assessed in human milk before the challenge and 1, 2, 3, and 4 hours after the commencement of the challenge. All but one of the infants with CMA showed symptoms of CMA during cow's milk challenge through human milk. There was a significant rise in the total number of immunoglobulin-secreting cells in the IgA and IgG classes associated with a positive cow's milk challenge response, but the proportions of peripheral blood B cells bearing CD19, CD23, CD19 and 23, CD5, or CD19 and CD5 were comparable. BLG levels were comparable in both study groups. Most of the infants with CMA reacted to cow's milk challenge through human milk. Hypersensitivity reactions to food antigens through human milk may be more common than previously thought.

  11. Human adaptation responses to a rapidly changing Arctic: A research context for building system resilience

    Science.gov (United States)

    Chapin, T.; Brinkman, T. J.

    2016-12-01

    Although human behavior accounts for more uncertainty in future trajectories in climate change than do biophysical processes, most climate-change research fails to include human actions in research design and implementation. This is well-illustrated in the Arctic. At the global scale, arctic processes strongly influence the strength of biophysical feedbacks between global human emissions and the rate of climate warming. However, most human actions in the arctic have little effect on these feedbacks, so research can contribute most effectively to reduction in arctic warming through improved understanding of the strength of arctic-global biophysical feedbacks, as in NASA's ABoVE program, and its effective communication to policy makers and the public. In contrast, at the local to regional scale within the arctic, human actions may influence the ecological and societal consequences of arctic warming, so research benefits from active stakeholder engagement in research design and implementation. Human communities and other stakeholders (government and NGOs) respond heterogeneously to socioeconomic and environmental change, so research that documents the range of historical and current adaptive responses to change provides insights on the resilience (flexibility of future options) of social-ecological processes in the arctic. Alaskan communities have attempted a range of adaptive responses to coastal erosion (e.g., seasonal migration, protection in place, relocation), wildfire (fire suppression to use of fire to manage wildlife habitat or landscape heterogeneity), declining sea ice (e.g., new hunting technology, sea ice observations and predictions), and changes in wildlife and fish availability (e.g., switch to harvest of alternative species, harvest times, or harvest locations). Research that draws on both traditional and western knowledge facilitates adaptation and predictions of the likely societal consequences of climate change in the Arctic. Effective inclusion of

  12. The validity of wireless iButtons and thermistors for human skin temperature measurement.

    Science.gov (United States)

    Smith, A D Harper; Crabtree, D R; Bilzon, J L J; Walsh, N P

    2010-01-01

    Skin temperature is a fundamental variable in human thermo-physiology, and yet skin temperature measurement remains impractical in most free-living, exercise and clinical settings, using currently available hard-wired methods. The purpose of this study was to compare wireless iButtons and hard-wired thermistors for human skin temperature measurement. In the first of two investigations, iButtons and thermistors monitored temperature in a controlled water bath (range: 10-40 degrees C) and were referenced against a certified, mercury thermometer. In the second investigation, eight healthy males completed three randomized trials (ambient temperature = 10 degrees C, 20 degrees C and 30 degrees C) while both devices recorded skin temperature at rest (in low and high wind velocities) and during cycle-ergometry exercise. The results are as follows. Investigation 1: both devices displayed very high validity correlation with the reference thermometer (r > 0.999). Prior to correction, the mean bias was +0.121 degrees C for iButtons and +0.045 degrees C for thermistors. Upon calibration correction the mean bias for iButtons and thermistors was not significantly different from zero bias. Interestingly, a typical error of the estimate of iButtons (0.043 degrees C) was 1.5 times less than that of thermistors (0.062 degrees C), demonstrating iButtons' lower random error. Investigation 2: the offset between iButton and thermistor readings was generally consistent across conditions; however, thermistor responses gave readings that were always closer to ambient temperature than those given by iButtons, suggesting potential thermistor drift towards environmental conditions. Mean temperature differences between iButtons and thermistors during resting trials ranged from 0.261 degrees C to 1.356 degrees C. Mean temperature differences between iButtons and thermistors during exercise were 0.989 degrees C (ambient temperature = 10 degrees C), 0.415 degrees C (ambient temperature = 20

  13. TLR-dependent human mucosal epithelial cell responses to microbial pathogens.

    Directory of Open Access Journals (Sweden)

    Paola eMassari

    2014-08-01

    Full Text Available AbstractToll-Like Receptor (TLR signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in humans as well as in animals. TLRs respond to specific microbial ligands and to danger signals produced by the host during infection, and initiate downstream cascades that activate both innate and adaptive immunity. TLRs are expressed by professional immune cells and by the large majority of non-hematopoietic cells, including epithelial cells. In epithelial tissues, TLR functions are particularly important because these sites are constantly exposed to microorganisms, due to their location at the host interface with the environment. While at these sites, specific defense mechanisms and inflammatory responses are initiated via TLR signaling against pathogens, suppression or lack of TLR activation is also observed in response to the commensal microbiota. The mechanisms by which TLR signaling is regulated in mucosal epithelial cells include differential expression and levels of TLRs (and their signaling partners, their cellular localization and positioning within the tissue in a fashion that favors responses to pathogens while dampening responses to commensals and maintaining tissue homeostasis in physiologic conditions. In this review, the expression and activation of TLRs in mucosal epithelial cells of several sites of the human body are examined. Specifically, the oral cavity, the ear canal and eye, the airways, the gut and the reproductive tract are discussed, along with how site-specific host defense mechanisms are implemented via TLR signaling.

  14. Mathematical modeling provides kinetic details of the human immune response to vaccination

    Directory of Open Access Journals (Sweden)

    Dustin eLe

    2015-01-01

    Full Text Available With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combine mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response is determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increases slowly, the slow increase can still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model describes well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization are derived from the population of circulating antibody-secreting cells. Taken together, our analysis provides novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlight challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  15. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    Science.gov (United States)

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

  16. Evaluation of human antibody responses to keyhole limpet hemocyanin (KLH) on a carbohydrate microarray

    Science.gov (United States)

    Oyelaran, Oyindasola; Gildersleeve, Jeffrey C.

    2012-01-01

    Purpose Keyhole limpet hemocyanin (KLH) is used as a vaccine adjuvant, as a carrier protein for small haptens, and as a treatment for bladder cancer. Immunization with KLH produces antibodies to tumor-associated carbohydrate antigens in animals, and these antibodies have been postulated as the basis of efficacy for bladder cancer treatment. The purpose of this study was to evaluate antibody responses to KLH in humans. Experimental Design A carbohydrate microarray was used to profile antibody responses in 14 individuals immunized with KLH plus alum adjuvant. Results 8/14 individuals produced antibodies to at least one tumor-associated carbohydrate antigen. Increases to Lewis X, Lewis Y, GA1di, GM3, and sialyl Lewis A were observed in certain individuals, but, in general, antibody profiles were highly variable. Pre-immunization antibody levels to a subset of array antigens had a statistically significant correlation with the magnitude of the antibody response to KLH. Conclusions and Clinical Relevance Antibodies to tumor-associated carbohydrate antigens can be produced in humans, but antibody profiles differ considerably from person to person, which may contribute to variable clinical responses with KLH. Pre-treatment antibody levels to certain antigens may be useful for predicting which patients will respond favorably to KLH. PMID:21137049

  17. Human physiological benefits of viewing nature: EEG responses to exact and statistical fractal patterns.

    Science.gov (United States)

    Hagerhall, C M; Laike, T; Küller, M; Marcheschi, E; Boydston, C; Taylor, R P

    2015-01-01

    Psychological and physiological benefits of viewing nature have been extensively studied for some time. More recently it has been suggested that some of these positive effects can be explained by nature's fractal properties. Virtually all studies on human responses to fractals have used stimuli that represent the specific form of fractal geometry found in nature, i.e. statistical fractals, as opposed to fractal patterns which repeat exactly at different scales. This raises the question of whether human responses like preference and relaxation are being driven by fractal geometry in general or by the specific form of fractal geometry found in nature. In this study we consider both types of fractals (statistical and exact) and morph one type into the other. Based on the Koch curve, nine visual stimuli were produced in which curves of three different fractal dimensions evolve gradually from an exact to a statistical fractal. The patterns were shown for one minute each to thirty-five subjects while qEEG was continuously recorded. The results showed that the responses to statistical and exact fractals differ, and that the natural form of the fractal is important for inducing alpha responses, an indicator of a wakefully relaxed state and internalized attention.

  18. Investigating the functionality of an OCT4-short response element in human induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Agustin Vega-Crespo

    2016-01-01

    Full Text Available Pluripotent stem cells offer great therapeutic promise for personalized treatment platforms for numerous injuries, disorders, and diseases. Octamer-binding transcription factor 4 (OCT4 is a key regulatory gene maintaining pluripotency and self-renewal of mammalian cells. With site-specific integration for gene correction in cellular therapeutics, use of the OCT4 promoter may have advantages when expressing a suicide gene if pluripotency remains. However, the human OCT4 promoter region is 4 kb in size, limiting the capacity of therapeutic genes and other regulatory components for viral vectors, and decreasing the efficiency of homologous recombination. The purpose of this investigation was to characterize the functionality of a novel 967bp OCT4-short response element during pluripotency and to examine the OCT4 titer-dependent response during differentiation to human derivatives not expressing OCT4. Our findings demonstrate that the OCT4-short response element is active in pluripotency and this activity is in high correlation with transgene expression in vitro, and the OCT4-short response element is inactivated when pluripotent cells differentiate. These studies demonstrate that this shortened OCT4 regulatory element is functional and may be useful as part of an optimized safety component in a site-specific gene transferring system that could be used as an efficient and clinically applicable safety platform for gene transfer in cellular therapeutics.

  19. Mathematical modeling provides kinetic details of the human immune response to vaccination.

    Science.gov (United States)

    Le, Dustin; Miller, Joseph D; Ganusov, Vitaly V

    2014-01-01

    With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response was determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increased slowly, the slow increase could still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model described well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization were derived from the population of circulating antibody-secreting cells. Taken together, our analysis provided novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlighted challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

  20. Unusual Volumetric Response of Human Red Blood Cells under Low Ionic Strength Conditions

    Directory of Open Access Journals (Sweden)

    Sergey V. Rudenko, PhD¹

    2013-06-01

    Full Text Available Human red blood cells (RBCs when suspended in a Low Ionic Strength medium (LIS demonstrate characteristic triphasic shape changes (morphological response, MR and become reduced in volume. Tahitian Tabari Noni juice (Tb, after being given during the terminal phase of MR, was shown to initiate an unusual cell response. This response can be described as a volumetric four-phasic response including first a shrinking phase, attributed to the initial sucrose-induced shrinkage during typical MR, a rapid first swelling phase, induced by application of the juice, followed spontaneously by the occurrence of a more prolonged second shrinking phase, which culminated in the swelling and hemolysis of the cells. All the phases of volumetric response can be independently regulated by chloride, DIDS, cations Ca2+, Ag+, Hg2+ or plasma. The second shrinking phase is not inhibited by clotrimazole, a known inhibitor of Gardos channels, and can be replicated by a mixture of two ionophores (valinomycin and CCCP, suggesting the involvement of the putative K+/H+ exchanger as a mechanism of this phase. We suggest that the erythrocyte membrane is equipped with additional molecular systems, poorly characterized at present, that regulate the cell shape and volume. The cell should, therefore, be considered as an “active” responsive system instead of a “passive” osmometer-like structure.

  1. Pupil size directly modulates the feedforward response in human primary visual cortex independently of attention.

    Science.gov (United States)

    Bombeke, Klaas; Duthoo, Wout; Mueller, Sven C; Hopf, Jens-Max; Boehler, C Nico

    2016-02-15

    Controversy revolves around the question of whether psychological factors like attention and emotion can influence the initial feedforward response in primary visual cortex (V1). Although traditionally, the electrophysiological correlate of this response in humans (the C1 component) has been found to be unaltered by psychological influences, a number of recent studies have described attentional and emotional modulations. Yet, research into psychological effects on the feedforward V1 response has neglected possible direct contributions of concomitant pupil-size modulations, which are known to also occur under various conditions of attentional load and emotional state. Here we tested the hypothesis that such pupil-size differences themselves directly affect the feedforward V1 response. We report data from two complementary experiments, in which we used procedures that modulate pupil size without differences in attentional load or emotion while simultaneously recording pupil-size and EEG data. Our results confirm that pupil size indeed directly influences the feedforward V1 response, showing an inverse relationship between pupil size and early V1 activity. While it is unclear in how far this effect represents a functionally-relevant adaptation, it identifies pupil-size differences as an important modulating factor of the feedforward response of V1 and could hence represent a confounding variable in research investigating the neural influence of psychological factors on early visual processing. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Engaging Human Rights in the Response to the Evolving Zika Virus Epidemic.

    Science.gov (United States)

    Rasanathan, Jennifer J K; MacCarthy, Sarah; Diniz, Debora; Torreele, Els; Gruskin, Sofia

    2017-04-01

    In late 2015, an increase in the number of infants born with microcephaly in poor communities in northeast Brazil prompted investigation of antenatal Zika infection as the cause. Zika now circulates in 69 countries, and has affected pregnancies of women in 29 countries. Public health officials, policymakers, and international organizations are considering interventions to address health consequences of the Zika epidemic. To date, public health responses have focused on mosquito vector eradication, sexual and reproductive health services, knowledge and technology including diagnostic test and vaccine development, and health system preparedness. We summarize responses to date and apply human rights and related principles including nondiscrimination, participation, the legal and policy context, and accountability to identify shortcomings and to offer suggestions for more equitable, effective, and sustainable Zika responses.

  3. No inflammatory gene-expression response to acute exercise in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Fredberg, Ulrich; Mikkelsen, Lone Ramer

    2013-01-01

    Although histology data favour the view of a degenerative nature of tendinopathy, indirect support for inflammatory reactions to loading in affected tendons exists. The purpose of the present study was to elucidate whether inflammatory signalling responses after acute mechanical loading were more....... All ultrasonographic outcomes were unchanged in response to acute exercise and not influenced by NSAID. The signalling for collagen and TGF-beta was upregulated after acute loading in tendinopathic tendon. In contrast to the hypothesis, inflammatory signalling was not exaggerated in tendinopathic...... pronounced in tendinopathic versus healthy regions of human tendon and if treatment with non-steroidal anti-inflammatory medications (NSAID's) reduces this response. Twenty-seven tendinopathy patients (>6 months) were randomly assigned to a placebo (n = 14) or NSAID (Ibumetin NYCOMED GmbH Plant Oranienburg...

  4. Local modulation of human brain responses by circadian rhythmicity and sleep debt.

    Science.gov (United States)

    Muto, Vincenzo; Jaspar, Mathieu; Meyer, Christelle; Kussé, Caroline; Chellappa, Sarah L; Degueldre, Christian; Balteau, Evelyne; Shaffii-Le Bourdiec, Anahita; Luxen, André; Middleton, Benita; Archer, Simon N; Phillips, Christophe; Collette, Fabienne; Vandewalle, Gilles; Dijk, Derk-Jan; Maquet, Pierre

    2016-08-12

    Human performance is modulated by circadian rhythmicity and homeostatic sleep pressure. Whether and how this interaction is represented at the regional brain level has not been established. We quantified changes in brain responses to a sustained-attention task during 13 functional magnetic resonance imaging sessions scheduled across the circadian cycle, during 42 hours of wakefulness and after recovery sleep, in 33 healthy participants. Cortical responses showed significant circadian rhythmicity, the phase of which varied across brain regions. Cortical responses also significantly decreased with accrued sleep debt. Subcortical areas exhibited primarily a circadian modulation that closely followed the melatonin profile. These findings expand our understanding of the mechanisms involved in maintaining cognition during the day and its deterioration during sleep deprivation and circadian misalignment. Copyright © 2016, American Association for the Advancement of Science.

  5. Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans

    DEFF Research Database (Denmark)

    Laker, R C; Garde, C; Camera, D M

    2017-01-01

    High fat feeding impairs skeletal muscle metabolic flexibility and induces insulin resistance, whereas exercise training exerts positive effects on substrate handling and improves insulin sensitivity. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects...... of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation. HFD markedly induced...... association between DNA methylation and gene expression changes were PYGM, which was epigenetically regulated in both groups, and ANGPTL4, which was regulated only following Ex. In conclusion, while short-term Ex did not prevent a HFD-induced inflammatory response, it provoked a genomic response that may...

  6. Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Ravn, P; Demissie, A; Eguale, T

    1999-01-01

    Human T cell responses to ESAT-6 and eight synthetic overlapping peptides were investigated in tuberculosis (TB) patients and control subjects from regions of high and low endemicity for TB. ESAT-6 was recognized by 65% of all tuberculin purified protein derivative-responsive TB patients, whereas...... only 2 of 29 bacille Calmette-Guérin-vaccinated Danish healthy donors recognized this molecule. In Ethiopia, a high frequency (58%) of healthy contacts of TB patients recognized ESAT-6. All of the peptides were recognized by some donors, indicating that the molecule holds multiple epitopes. Danish...... and Ethiopian patients differed in the fine specificity of their peptide responses. Recognition of the C-terminal region (aa 72-95) was predominant in Danish patients, whereas recognition of aa 42-75 was predominant in Ethiopia. The relationship of these differences to the distribution of HLA types in the two...

  7. Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics.

    Science.gov (United States)

    Sarkar, Rajiv; Ajjampur, Sitara S; Ward, Honorine D; Kang, Gagandeep; Naumova, Elena N

    2012-01-03

    Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking. In this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots. We provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection. The use of traditional

  8. Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics

    Directory of Open Access Journals (Sweden)

    Sarkar Rajiv

    2012-01-01

    Full Text Available Abstract Background Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking. Methods In this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre and after (post an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots. Results We provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age

  9. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    Energy Technology Data Exchange (ETDEWEB)

    Jetten, Marlon J.A.; Gaj, Stan [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Ruiz-Aracama, Ainhoa [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Kok, Theo M. de [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Delft, Joost H.M. van, E-mail: j.vandelft@maastrichtuniversity.nl [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Lommen, Arjen [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Someren, Eugene P. van [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Jennen, Danyel G.J.; Claessen, Sandra M. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Peijnenburg, Ad A.C.M. [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Stierum, Rob H. [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Kleinjans, Jos C.S. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands)

    2012-03-15

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques

  10. Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

    Science.gov (United States)

    Brown, Aisling F.; Leech, John M.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2014-01-01

    In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity. PMID:24409186

  11. Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2015-01-01

    Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to

  12. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Aguirre

    2007-06-01

    Full Text Available RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA. Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA.RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3. Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06% and volume (8.2 +/- 0.8 cm(3 of activation within the lateral gyrus (p < 0.005 for both. Cortical recovery occurred rapidly (within a month of treatment and was persistent (as long as 2.5 y after treatment. Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm was within the normal range (3.2 +/- 0.3 mm, and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005. Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 +/- 1.2 cm(3 compared to controls

  13. Human Norovirus and Its Surrogates Induce Plant Immune Response in Arabidopsis thaliana and Lactuca sativa.

    Science.gov (United States)

    Markland, Sarah M; Bais, Harsh; Kniel, Kalmia E

    2017-08-01

    Human norovirus is the leading cause of foodborne illness worldwide with the majority of outbreaks linked to fresh produce and leafy greens. It is essential that we thoroughly understand the type of relationship and interactions that take place between plants and human norovirus to better utilize control strategies to reduce transmission of norovirus in the field onto plants harvested for human consumption. In this study the expression of gene markers for the salicylic acid (SA) and jasmonic acid (JA) plant defense pathways was measured and compared in romaine lettuce (Lactuca sativa) and Arabidopsis thaliana Col-0 plants that were inoculated with Murine Norovirus-1, Tulane Virus, human norovirus GII.4, or Hank's Balanced Salt Solution (control). Genes involving both the SA and JA pathways were expressed in both romaine lettuce and A. thaliana for all three viruses, as well as controls. Studies, including gene expression of SA- and JA-deficient A. thaliana mutant lines, suggest that the JA pathway is more likely involved in the plant immune response to human norovirus. This research provides the first pieces of information regarding how foodborne viruses interact with plants in the preharvest environment.

  14. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tetz, Lauren M., E-mail: ltetz@umich.edu [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Cheng, Adrienne A.; Korte, Cassandra S. [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Giese, Roger W.; Wang, Poguang [Department of Pharmaceutical Sciences, Northeastern University, 360 Huntingon Ave, Boston, MA 02115 (United States); Harris, Craig; Meeker, John D.; Loch-Caruso, Rita [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States)

    2013-04-01

    Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ► MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ► MEHP induced expression of PTGS2, a gene

  15. Human responses to wave slamming vibration on a polar supply and research vessel.

    Science.gov (United States)

    Omer, H; Bekker, A

    2018-02-01

    A polar supply and research vessel is pre-disposed to wave slamming which has caused complaints among crew and researchers regarding interference with sleep, equipment use and research activities. The present work undertook to survey passenger claims of sleep interference, disturbed motor tasks and equipment damage as a result of wave slamming during normal operations of this vessel. The hypothesis was investigated that whole-body vibration metrics from ISO 2631-1 are potentially suitable for the prediction of human slamming complaints. Full-scale acceleration measurements were performed and wave slamming events were subsequently identified from the human weighted acceleration time histories. A daily diary survey was also conducted to gather the human response. The vibration caused by wave slamming was found to be strongly correlated with sleep disturbances and activity interference. Sleep and equipment use were found to be the most affected parameters by slamming. Daily vibration dose values were determined by accumulating the vibration as a result of slamming over 24 h periods. This metric accounted for increased magnitudes and frequency of slamming incidents and proved to be the best metric to represent human responses to slamming vibration. The greatest percentage of activities affected by slamming related to sleep regardless of daily cumulative VDV magnitude. More than 50% of the recorded responses related to sleep when the daily cumulative VDV ranged between 8.0 m/s1.75-10.0 m/s1.75. The peak vertical vibration levels recorded on the vessel reach magnitudes which are associated with sleep disturbance in environments where acoustic noise is present. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses.

    Science.gov (United States)

    Clinard, Christopher G; Hodgson, Sarah L; Scherer, Mary Ellen

    2017-04-01

    The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (SπNo or SoNπ, respectively), relative to detection when signal and noise are in identical phase at each ear (SoNo). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: SoNo, SπNo, and SoNπ. BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21-26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the SπNo condition relative to SoNo and SoNπ conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., SoNo amplitude-SπNo amplitude) were significantly predictive of behavioral SπNo BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.

  17. Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

    Science.gov (United States)

    Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

    2008-06-01

    Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

  18. Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach.

    Science.gov (United States)

    Kelsen, Steven G; Duan, Xunbao; Ji, Rong; Perez, Oscar; Liu, Chunli; Merali, Salim

    2008-05-01

    Cigarette smoking, which exposes the lung to high concentrations of reactive oxidant species (ROS) is the major risk factor for chronic obstructive pulmonary disease (COPD). Recent studies indicate that ROS interfere with protein folding in the endoplasmic reticulum and elicit a compensatory response termed the "unfolded protein response" (UPR). The importance of the UPR lies in its ability to alter expression of a variety of genes involved in antioxidant defense, inflammation, energy metabolism, protein synthesis, apoptosis, and cell cycle regulation. The present study used comparative proteomic technology to test the hypothesis that chronic cigarette smoking induces a UPR in the human lung. Studies were performed on lung tissue samples obtained from three groups of human subjects: nonsmokers, chronic cigarette smokers, and ex-smokers. Proteomes of lung samples from chronic cigarette smokers demonstrated 26 differentially expressed proteins (20 were up-regulated, 5 were down-regulated, and 1 was detected only in the smoking group) compared with nonsmokers. Several UPR proteins were up-regulated in smokers compared with nonsmokers and ex-smokers, including the chaperones, glucose-regulated protein 78 (GRP78) and calreticulin; a foldase, protein disulfide isomerase (PDI); and enzymes involved in antioxidant defense. In cultured human airway epithelial cells, GRP78 and the UPR-regulated basic leucine zipper, transcription factors, ATF4 and Nrf2, which enhance expression of important anti-oxidant genes, increased rapidly (< 24 h) with cigarette smoke extract. These data indicate that cigarette smoke induces a UPR response in the human lung that is rapid in onset, concentration dependent, and at least partially reversible with smoking cessation. We speculate that activation of a UPR by cigarette smoke may protect the lung from oxidant injury and the development of COPD.

  19. Face-Likeness and Image Variability Drive Responses in Human Face-Selective Ventral Regions

    Science.gov (United States)

    Davidenko, Nicolas; Remus, David A.; Grill-Spector, Kalanit

    2012-01-01

    The human ventral visual stream contains regions that respond selectively to faces over objects. However, it is unknown whether responses in these regions correlate with how face-like stimuli appear. Here, we use parameterized face silhouettes to manipulate the perceived face-likeness of stimuli and measure responses in face- and object-selective ventral regions with high-resolution fMRI. We first use “concentric hyper-sphere” (CH) sampling to define face silhouettes at different distances from the prototype face. Observers rate the stimuli as progressively more face-like the closer they are to the prototype face. Paradoxically, responses in both face- and object-selective regions decrease as face-likeness ratings increase. Because CH sampling produces blocks of stimuli whose variability is negatively correlated with face-likeness, this effect may be driven by more adaptation during high face-likeness (low-variability) blocks than during low face-likeness (high-variability) blocks. We tested this hypothesis by measuring responses to matched-variability (MV) blocks of stimuli with similar face-likeness ratings as with CH sampling. Critically, under MV sampling, we find a face-specific effect: responses in face-selective regions gradually increase with perceived face-likeness, but responses in object-selective regions are unchanged. Our studies provide novel evidence that face-selective responses correlate with the perceived face-likeness of stimuli, but this effect is revealed only when image variability is controlled across conditions. Finally, our data show that variability is a powerful factor that drives responses across the ventral stream. This indicates that controlling variability across conditions should be a critical tool in future neuroimaging studies of face and object representation. PMID:21823208

  20. Factor structure of the human gamma band oscillatory response to visual (contrast) stimulation.

    Science.gov (United States)

    Carozzo, Simone; De Carli, Fabrizio; Beelke, Manolo; Saturno, Moreno; Garbarino, Sergio; Martello, Cristina; Sannita, Walter G

    2004-07-01

    Visual contrast stimulation evokes in man an oscillatory mass response at approximately 20.0-35.0 Hz, consistent with stimulus-dependent synchronous oscillations in multiunit animal recordings from visual cortex, but shorter in duration and phase-locked to stimulus. A factor analysis was applied to characterize the signal structure under stimulus conditions inducing an oscillatory response and to identify possible subcomponents in normal volunteers. Contrast stimuli were gratings with a sinusoidal luminance profile (9.0 degrees; 5.0 cycle/degree; 80% contrast; reversal 1.06 Hz). The amplitude spectrum of the signal was computed by Discrete Fourier Transform (DFT) and the oscillatory response was separated from the corresponding visually evoked potential (VEP) by DFT high-pass filter at 19.0 Hz. Nine consecutive waves were identified in all subjects (60 volunteers), with amplitudes/latencies consistent with normative studies. A factor analysis was computed 1- in the frequency domain, on the amplitude values of the signal components (2 Hz resolution), and 2- in the time domain, on the latencies/amplitudes of the averaged VEP and oscillatory responses. (1) Two non-overlapping factors accounted for the approximately 2-20.0 and approximately 20.0-40.0 Hz signal components, with separation of the approximately 20.0-35.0 Hz oscillatory response from low frequency VEPs. (2) Two factors on latencies and one factor on amplitudes (independent of each other and from those of VEPs) accounted for the average approximately 20.0-35.0 Hz oscillatory response. The factor structure further indicates an oscillatory structure and some independence from conventional VEPs of the human oscillatory response to contrast, with a separation between the oscillatory response early and late waves possibly reflecting functional differences.

  1. Evaluation of two algorithms for detecting human frequency-following responses to voice pitch.

    Science.gov (United States)

    Jeng, Fuh-Cherng; Hu, Jiong; Dickman, Brenda; Lin, Ching-Yu; Lin, Chia-Der; Wang, Ching-Yuan; Chung, Hsiung-Kwang; Li, Ximing

    2011-01-01

    Voice pitch carries important cues for speech perception in humans. Recent studies have shown the feasibility of recording the frequency-following response (FFR) to voice pitch in normal-hearing listeners. The presence of such a response, however, has been dependent on subjective interpretation of experimenters. The purpose of this study was to develop and test an automated procedure including a control-experimental protocol and response-threshold criteria suitable for extracting FFRs to voice pitch, and compare the results to human judgments. A set of four Mandarin tones (Tone 1 flat; Tone 2 rising; Tone 3 dipping; and Tone 4 falling) were prepared to reflect the four contrastive pitch contours. Two distinctive algorithms, short-term autocorrelation in the time domain and narrow-band spectrogram in the frequency domain, were used to estimate the Frequency Error, Slope Error, Tracking Accuracy, Pitch Strength and Pitch-Noise Ratio of the recordings from individual listeners as well as the power and false-positive rates of each algorithm. Eleven native speakers (five males; age: mean ± SD = 31.4 ± 4.7 years) of Mandarin Chinese were recruited. The results demonstrated that both algorithms were suitable for extracting FFRs and the objective measures showed comparable results to human judgments. The automated procedure used in this study, including the use of the control-experimental protocol and response thresholds used for each of the five objective indices, can be used for difficult-to-test patients and may prove to be useful as an assessment and diagnostic method in both clinical and basic research efforts.

  2. NK Cell Responses to Human Tick-Borne Encephalitis Virus Infection.

    Science.gov (United States)

    Blom, Kim; Braun, Monika; Pakalniene, Jolita; Lunemann, Sebastian; Enqvist, Monika; Dailidyte, Laura; Schaffer, Marie; Lindquist, Lars; Mickiene, Aukse; Michaëlsson, Jakob; Ljunggren, Hans-Gustaf; Gredmark-Russ, Sara

    2016-10-01

    Tick-borne encephalitis virus (TBEV) is a flavivirus that is transferred to humans by infected ticks. The virus causes tick-borne encephalitis, a severe infection of the CNS with a high risk for long-lasting sequelae. Currently, no treatment exists for the disease. Understanding the cellular immune response to this infection is important to gain further understanding into the pathogenesis, treatment, and prevention of the disease. NK cells are known to participate in the control of viral infections. We performed a longitudinal analysis of the human NK cell response to TBEV infection in a cohort of infected individuals from the onset of severe clinical symptoms to the convalescence phase. NK cell activation, as measured by expression of Ki67, was apparent at the time of hospitalization. By 3 wk after hospitalization, it decreased to levels seen in healthy controls. Concomitant with the increase in NK cell activation, augmented levels of IL-12, IL-15, IL-18, IFN-γ, and TNF were detected in patient plasma. This TBEV-induced NK cell activation was restricted predominantly to differentiated CD57(+)CD56(dim) NK cells. Functionally, CD56(dim) NK cells responded poorly to target cells at the time of hospitalization, but they recovered functional capacity to control levels during the convalescent phase. In contrast, the responsiveness of NK cells to cytokine stimulation remained intact throughout the disease. These findings demonstrate that NK cells respond to TBEV infection with characteristics that are distinct from those of other human viral infections and provide insights into the NK cell response to clinical TBEV infection. Copyright © 2016 by The American Association of Immunologists, Inc.

  3. Renal and Cardio-Endocrine Responses in Humans to Simulated Microgravity

    Science.gov (United States)

    Williams, Gordon H.

    1999-01-01

    mediator of the adaptive cardio-renal responses observed during space missions and is a special focus of this project. Thus, the overall goal of this project is to assess the impact of microgravity and sleep deprivation in humans on volume-regulating systems. To achieve this overall objective, we are evaluating renal blood flow and the status and responsiveness of the volume- regulating systems (RAAS, atrial natriuretic peptide and vasopressin), and the adrenergic system (plasma and urine catecholamines) in both simulated microgravity and normal gravity with and -Without sleep deprivation. Furthermore, the responses of the volume homeostatic mechanisms to acute stimulation by upright tilt testing, standing and exercise are being evaluated before and after achieving equilibrium with these interventions.

  4. Comparing human T cell and NK cell responses in viral-based malaria vaccine trials.

    Science.gov (United States)

    Berthoud, Tamara K; Fletcher, Helen; Porter, David; Thompson, Fiona; Hill, Adrian V S; Todryk, Stephen M

    2009-12-10

    Vaccination with viral-based vaccines continues to hold promise for the prevention of malaria. Whilst antigen-specific T cell responses are considered a major aim of such an approach, a role for induced NK cells as anti-malarial effector cells, or in shaping T cell responses, has received less attention. In this study naïve human volunteers were vaccinated in a prime-boost vaccination regimen comprising recombinant viral vectors fowlpox (FP9) and modified vaccinia Ankara (MVA) encoding liver-stage antigens, or a virosome vaccine. Significant T cell responses specific for the vectored vaccine antigens were demonstrated by IFNgamma ELISPOT and intracellular cytokine staining (ICS) for IFNgamma and IL-2, the ICS being associated with increased time to parasitaemia following subsequent challenge. Numbers of CD56(bright) lymphocytes increased significantly following vaccination, as did CD3(+) CD56(+) lymphocytes, whilst CD56(dim) cells did not. No such increases were seen with the virosome vaccine. There was no significant correlation of these CD56(+) populations with the antigen-specific T cell responses nor time to parasitaemia. To investigate pathways of immune activation that could contribute to these lymphocyte responses, viral vectors were shown in vitro to efficiently infect APCs but not lymphocytes, and stimulated inflammatory cytokines such as type I interferons. In conclusion, measuring antigen-specific T cells is more meaningful than NK cells in these vaccination regimens.

  5. Movements modulate the reflex responses of human flexor pollicis longus to stretch.

    Science.gov (United States)

    Wallace, C J; Miles, T S

    1998-01-01

    The reflex responses to brisk, ramp stretch perturbations of the human flexor pollicis longus muscle (FPL) were recorded during isometric and slow concentric or eccentric contractions at similar levels of muscle excitation. The subjects flexed their thumb to push down against a thumb-rest, whose position was controlled by a servo-controlled motor. In different runs, the stretch perturbations were imposed when the thumb-rest was stationary (isometric) or was flexing or extending the interphalangeal joint of the thumb at a constant velocity, i.e. during concentric or eccentric contractions of FPL. The latency of the most prominent component of the electromyographic reflex in the isometrically contracting muscle was about 60 ms, measured from the command signal. The amplitude of this response was sharply reduced during the non-isometric contractions. While not dependent on the direction, this modulation of the reflex response increased with the speed of active movement of the interphalangeal joint (flexion or extension). The response was greatly reduced during concentric or eccentric movements as slow as 1.6 mm x s[-1] (approximately 5 degrees x s (-1) at the joint). When the force rather than the position of the thumb-rest was servo-controlled, the stretch response to perturbation again diminished with speed in a self-paced flexion task, compared with an isometric "hold" condition.

  6. Analysis of non-linear response of the human body to vertical whole-body vibration.

    Science.gov (United States)

    Tarabini, Marco; Solbiati, Stefano; Moschioni, Giovanni; Saggin, Bortolino; Scaccabarozzi, Diego

    2014-01-01

    The human response to vibration is typically studied using linear estimators of the frequency response function, although different literature works evidenced the presence of non-linear effects in whole-body vibration response. This paper analyses the apparent mass of standing subjects using the conditioned response techniques in order to understand the causes of the non-linear behaviour. The conditioned apparent masses were derived considering models of increasing complexity. The multiple coherence function was used as a figure of merit for the comparison between the linear and the non-linear models. The apparent mass of eight male subjects was studied in six configurations (combinations of three vibration magnitudes and two postures). The contribution of the non-linear terms was negligible and was endorsed to the change of modal parameters during the test. Since the effect of the inter-subject variability was larger than that due to the increase in vibration magnitude, the biodynamic response should be more meaningfully modelled using a linear estimator with uncertainty rather than looking for a non-linear modelling.

  7. Deciphering the Contribution of Human Meningothelial Cells to the Inflammatory and Antimicrobial Response at the Meninges

    Science.gov (United States)

    Royer, Pierre-Joseph; Rogers, Andrew J.; Wooldridge, Karl G.; Tighe, Patrick; Mahdavi, Jafar; Rittig, Michael G.

    2013-01-01

    We have investigated the response of primary human meningothelial cells to Neisseria meningitidis. Through a transcriptome analysis, we provide a comprehensive examination of the response of meningothelial cells to bacterial infection. A wide range of chemokines are elicited which act to attract and activate the main players of innate and adaptive immunity. We showed that meningothelial cells expressed a high level of Toll-like receptor 4 (TLR4), and, using a gene silencing strategy, we demonstrated the contribution of this pathogen recognition receptor in meningothelial cell activation. Secretion of interleukin-6 (IL-6), CXCL10, and CCL5 was almost exclusively TLR4 dependent and relied on MyD88 and TRIF adaptor cooperation. In contrast, IL-8 induction was independent of the presence of TLR4, MyD88, and TRIF. Transcription factors NF-κB p65, p38 mitogen-activated protein kinase (MAPK), Jun N-terminal protein kinase (JNK1), IRF3, and IRF7 were activated after contact with bacteria. Interestingly, the protein kinase IRAK4 was found to play a minor role in the meningothelial cell response to Neisseria infection. Our work highlights the role of meningothelial cells in the development of an immune response and inflammation in the central nervous system (CNS) in response to meningococcal infection. It also sheds light on the complexity of intracellular signaling after TLR triggering. PMID:24002066

  8. Insights into Human Astrocyte Response to H5N1 Infection by Microarray Analysis

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    Xian Lin

    2015-05-01

    Full Text Available Influenza virus infects not only the respiratory system but also the central nervous system (CNS, leading to influenza-associated encephalopathy and encephalitis. Astrocytes are essential for brain homeostasis and neuronal function. These cells can also be infected by influenza virus. However, genome-wide changes in response to influenza viral infection in astrocytes have not been defined. In this study, we performed gene profiling of human astrocytes in response to H5N1. Innate immune and pro-inflammatory responses were strongly activated at 24 h post-infection (hpi. Antiviral genes, as well as several cytokines and chemokines, including CXCL9, CXCL10, and CXCL11, were robustly induced. Phosphorylation of p65 and p38 can be activated by viral infection, suggesting their potential critical roles in H5N1-induced pro-inflammatory response. Moreover, H5N1 infection significantly upregulated the gene expressions related to the neuroactive ligand-receptor interaction pathway at 24 hpi, such as MC2R, CHRNG, P2RY13, GABRA1, and HRH2, which participant in synaptic transmission and may take part in CNS disorders induced by H5N1 infection. Targeting key components of innate immune response and the neuroactive ligand-receptor interaction pathway may provide a strategy to control H5N1-induced encephalopathy and encephalitis. This research can contribute to the understanding of H5N1 pathogenesis in astrocytes.

  9. Family history of alcoholism and the human brain response to oral sucrose.

    Science.gov (United States)

    Eiler, William J A; Dzemidzic, Mario; Soeurt, Christina M; Carron, Claire R; Oberlin, Brandon G; Considine, Robert V; Harezlak, Jaroslaw; Kareken, David A

    2018-01-01

    A heightened hedonic response to sweet tastes has been associated with increased alcohol preference and alcohol consumption in both humans and animals. The principal goal of this study was to examine blood oxygenation level dependent (BOLD) activation to high- and low-concentration sweet solutions in subjects who are either positive (FHP) or negative (FHN) for a family history of alcoholism. Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8 ± 1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste test and underwent functional magnetic resonance imaging (fMRI) during oral delivery of water, 0.83 M, and 0.10 M sucrose. Sucrose compared to water produced robust activation in primary gustatory cortex, ventral insula, amygdala, and ventral striatum. FHP subjects displayed greater bilateral amygdala activation than FHN subjects in the low sucrose concentration (0.10 M). In secondary analyses, the right amygdala response to the 0.10 M sucrose was greatest in FHP women. When accounting for group differences in drinks per week, the family history groups remained significantly different in their right amygdala response to 0.10 M sucrose. Our findings suggest that the brain response to oral sucrose differs with a family history of alcoholism, and that this response to a mildly reinforcing primary reward might be an endophenotypic marker of alcoholism risk.

  10. ATM-mediated mitochondrial damage response triggered by nuclear DNA damage in normal human lung fibroblasts.

    Science.gov (United States)

    Shimura, Tsutomu; Sasatani, Megumi; Kawai, Hidehiko; Kamiya, Kenji; Kobayashi, Junya; Komatsu, Kenshi; Kunugita, Naoki

    2017-11-03

    Ionizing radiation (IR) elevates mitochondrial oxidative phosphorylation (OXPHOS) in response to the energy requirement for DNA damage responses. Reactive oxygen species (ROS) released during mitochondrial OXPHOS may cause oxidative damage to mitochondria in irradiated cells. In this paper, we investigated the association between nuclear DNA damage and mitochondrial damage following IR in normal human lung fibroblasts. In contrast to low-doses of acute single radiation, continuous exposure of chronic radiation or long-term exposure of fractionated radiation (FR) induced persistent Rad51 and γ-H2AX foci at least 24 hours after IR in irradiated cells. Additionally, long-term FR increased mitochondrial ROS accompanied with enhanced mitochondrial membrane potential (ΔΨm) and mitochondrial complex IV (cytochrome c oxidase) activity. Mitochondrial ROS released from the respiratory chain complex I caused oxidative damage to mitochondria. Inhibition of ATM kinase or ATM loss eliminated nuclear DNA damage recognition and mitochondrial radiation responses. Consequently, nuclear DNA damage activates ATM which in turn increases ROS level and subsequently induces mitochondrial damage in irradiated cells. In conclusion, we demonstrated that ATM is essential in the mitochondrial radiation responses in irradiated cells. We further demonstrated that ATM is involved in signal transduction from nucleus to the mitochondria in response to IR.

  11. Evolution and behavioural responses to human-induced rapid environmental change

    Science.gov (United States)

    Sih, Andrew; Ferrari, Maud C O; Harris, David J

    2011-01-01

    Almost all organisms live in environments that have been altered, to some degree, by human activities. Because behaviour mediates interactions between an individual and its environment, the ability of organisms to behave appropriately under these new conditions is crucial for determining their immediate success or failure in these modified environments. While hundreds of species are suffering dramatically from these environmental changes, others, such as urbanized and pest species, are doing better than ever. Our goal is to provide insights into explaining such variation. We first summarize the responses of some species to novel situations, including novel risks and resources, habitat loss/fragmentation, pollutants and climate change. Using a sensory ecology approach, we present a mechanistic framework for predicting variation in behavioural responses to environmental change, drawing from models of decision-making processes and an understanding of the selective background against which they evolved. Where immediate behavioural responses are inadequate, learning or evolutionary adaptation may prove useful, although these mechanisms are also constrained by evolutionary history. Although predicting the responses of species to environmental change is difficult, we highlight the need for a better understanding of the role of evolutionary history in shaping individuals’ responses to their environment and provide suggestion for future work. PMID:25567979

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

    Science.gov (United States)

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

    2017-01-01

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

  13. Characterization of ionizing radiation-induced unfolded protein response in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ju; Lee, Yoon Jin; Kang, Seong Man [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-04-15

    Misfolded or unfolded proteins within the endoplasmic reticulum (ER stress), viral infection, or amino acid deprivation induce eukaryotic translation initiation factor 2α phosphorylation (eIF2α) in eukaryotic cells, repressing global protein synthesis coincident with preferential translation of activating transcription factor 4 (ATF4). ATF4 is a transcriptional activator of genes involved in amino acid metabolism, cellular redox homeostasis, and regulation of apoptosis. When the eIF2α/ATF4 pathway is initiated by ER stress, the pathway is referred toas the unfolded protein response (UPR). In addition to DNA, proteins may be initial and important targets of ionizing radiation (IR), and the damaged protein can trigger ER stress pathway. Recent investigations suggested that IR induces ER stress followed by UPR in various cell types including intestinal epithelial cells. We conducted this study to determine whether IR can activate UPR in human vascular endothelial cells. Our data have shown that IR increased PERK-dependent eIF2α phosphorylation accompanied by induction in ATF4 protein levels in human vascular endothelial cells without alterations in expressions of XBP-1s and GRP78. Based on these data, we suggest that IR selectively activates PERK branch of unfolded protein response in human vascular endothelial cells.

  14. Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response.

    Science.gov (United States)

    Federici Canova, Donata; Pavlov, Anton M; Norling, Lucy V; Gobbetti, Thomas; Brunelleschi, Sandra; Le Fauder, Pauline; Cenac, Nicolas; Sukhorukov, Gleb B; Perretti, Mauro

    2015-11-10

    Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with α2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of α2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble α2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of α2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of α2MG with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Susceptibility and response of human blood monocyte subsets to primary dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Kok Loon Wong

    Full Text Available Human blood monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood monocytes are heterogeneous and divided into CD16(- and CD16(+ subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if monocyte subsets differentially contribute to dengue protection and pathogenesis. Here, we compared the susceptibility and response of the human CD16(- and CD16(+ blood monocyte subsets to primary dengue virus in vitro. We found that both monocyte subsets were equally susceptible to dengue virus (DENV2 NGC, and capable of supporting the initial production of new infective virus particles. Both monocyte subsets produced anti-viral factors, including IFN-α, CXCL10 and TRAIL. However, CD16(+ monocytes were the major producers of inflammatory cytokines and chemokines in response to dengue virus, including IL-1β, TNF-α, IL-6, CCL2, 3 and 4. The susceptibility of both monocyte subsets to infection was increased after IL-4 treatment, but this increase was more profound for the CD16(+ monocyte subset, particularly at early time points after virus exposure. These findings reveal the differential role that monocyte subsets might play during dengue disease.

  16. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Directory of Open Access Journals (Sweden)

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

  17. Innate Response Activator (IRA B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro.

    Directory of Open Access Journals (Sweden)

    Nico Chiappini

    Full Text Available Innate response activator (IRA B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA B cells in tonsils. We show that CD19⁺CD20⁺GM-CSF⁺ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19⁺CD20⁺GM-CSF⁻ B cells. These cells reside within the B cell follicles, are mostly IgM⁺IgD⁺, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.

  18. Innate Response Activator (IRA) B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro.

    Science.gov (United States)

    Chiappini, Nico; Cantisani, Rocco; Pancotto, Laura; Ruggiero, Paolo; Rosa, Domenico; Manetti, Andrea; Romano, Antonio; Montagnani, Francesca; Bertholet, Sylvie; Castellino, Flora; Del Giudice, Giuseppe

    2015-01-01

    Innate response activator (IRA) B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA) B cells in tonsils. We show that CD19⁺CD20⁺GM-CSF⁺ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19⁺CD20⁺GM-CSF⁻ B cells. These cells reside within the B cell follicles, are mostly IgM⁺IgD⁺, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.

  19. Histological assessment of pulpal responses to resin modified glass ionomer cements in human teeth

    Directory of Open Access Journals (Sweden)

    Ali Eskandarizadeh

    2015-01-01

    Full Text Available Background: The biocompatibility of resin-modified glass ionomers (RMGIs as a lining material is still under question. The present study evaluated the response of the pulp-dentin complex following application of resin-modified glass-ionomer cement, calcium hydroxide and conventional glass-ionomer in deep cavities prepared in human teeth. Materials and Methods: In this controlled clinical trial, 30 deep class V buccal cavities (3 mm × 2 mm × 2 mm were prepared in human premolars treatment planned to be extracted for orthodontic reasons and divided into 3 groups. Groups were lined by a RMGI (Vivaglass, conventional glass Ionomer (Ionocid and calcium hydroxide respectively. The cavities were subsequently filled with amalgam. Each group was then divided into two sub-groups according to time intervals 5 and 30 days. The patients were referred to Kerman Dental School and in accordance with orthodontic treatment plan; premolars were extracted and then prepared for histological assessment. The sections were stained with hematoxylin and eosin and periodic acid Schiff techniques. All of the samples were examined using a number of criteria including odontoblastic changes, inflammatory cells response, reactionary dentin formation and presence of microorganisms. The data were analyzed by Kruskal-Wallis and Mann-Whitney tests. P 0.05. Conclusion: Ionocid and Vivaglass resin-modified glass ionomers can be used as lining materials in human teeth.

  20. Complicated grief and posttraumatic stress disorder in humans' response to the death of pets/animals.

    Science.gov (United States)

    Adrian, Julie A Luiz; Deliramich, Aimee N; Frueh, B Christopher

    2009-01-01

    The present exploratory project represents a cross-sectional study designed to determine the percentage of people reporting significant symptoms of complicated grief (CG) and/or posttraumatic stress disorder (PTSD) in response to the death of companion pets/animals. Human participants (N = 106) were sampled from a veterinary clinic. Fifty-two percent of participants had lost one to three pets from natural causes, 60% had never lost a pet to euthanasia, and 37% had lost one to three pets to euthanasia. The study suggests that many people experience significant attachment to their pets/animals and experience significant features of grief reactions (about 20%) after the death of a pet/animal. However, the percentage of people experiencing major pathological disruption is relatively low (grief and sadness are relatively common human responses to the death of companion pets/animals and last 6 months or more for about 30% of those sampled. Severe pathological reactions do occur but are quite rare among human survivors. Implications for mental health clinicians working with affected populations are discussed.

  1. Gene expression in response to cyclic mechanical stretch in primary human dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    Maria Reichenbach

    2014-12-01

    Full Text Available The human dermal skin is permanently exposed to mechanical stress, for instance during facial expression, which might cause wrinkles with age. Cyclic mechanical stretching of cells results in cellular and cytoskeleton alignment perpendicular to the stretch direction regulating cellular response. With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. Here, the transcription activity of the genome in response to cyclic mechanical stress was measured using DNA microarray technology with Agilent SurePrint G3 Human GE 8x60k Microarrays, based on the overall measurement of the mRNA. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned. Gene expression data of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology and were deposited at http://www.ncbi.nlm.nih.gov/geo with the accession number GSE58389.

  2. Mitochondrial fragmentation in human macrophages attenuates palmitate-induced inflammatory responses.

    Science.gov (United States)

    Zezina, Ekaterina; Snodgrass, Ryan G; Schreiber, Yannick; Zukunft, Sven; Schürmann, Christoph; Heringdorf, Dagmar Meyer Zu; Geisslinger, Gerd; Fleming, Ingrid; Brandes, Ralf P; Brüne, Bernhard; Namgaladze, Dmitry

    2018-02-02

    Macrophages in adipose tissue contribute to inflammation and the development of insulin resistance in obesity. Exposure of macrophages to saturated fatty acids alters cell metabolism and activates pro-inflammatory signaling. How fatty acids influence macrophage mitochondrial dynamics is unclear. We investigated the mechanism of palmitate-induced mitochondrial fragmentation and its impact on inflammatory responses in primary human macrophages. Fatty acids, such as palmitate, caused mitochondrial fragmentation in human macrophages. Increased mitochondrial fragmentation was also observed in peritoneal macrophages from hyperlipidemic apolipoprotein E knockout mice. Fatty acid-induced mitochondrial fragmentation was independent of the fatty acid chain saturation and required dynamin-related protein 1 (DRP1). Mechanistically, mitochondrial fragmentation was regulated by incorporation of palmitate into mitochondrial phospholipids and their precursors. Palmitate-induced endoplasmic reticulum stress and loss of mitochondrial membrane potential did not contribute to mitochondrial fragmentation. Macrophages treated with palmitate maintained intact mitochondrial respiration and ATP levels. Pharmacological or genetic inhibition of DRP1 enhanced palmitate-induced mitochondrial ROS production, c-Jun phosphorylation, and inflammatory cytokine expression. Our results indicate that mitochondrial fragmentation is a protective mechanism attenuating inflammatory responses induced by palmitate in human macrophages. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Cardiovascular regulation in humans in response to oscillatory lower body negative pressure

    Science.gov (United States)

    Levenhagen, D. K.; Evans, J. M.; Wang, M.; Knapp, C. F.

    1994-01-01

    The frequency response characteristics of human cardiovascular regulation during hypotensive stress have not been determined. We therefore exposed 10 male volunteers to seven frequencies (0.004-0.1 Hz) of oscillatory lower body negative pressure (OLBNP; 0-50 mmHg). Fourier spectra of arterial pressure (AP), central venous pressure (CVP), stroke volume (SV), cardiac output (CO), heart rate (HR), and total peripheral resistance (TPR) were determined and first harmonic mean, amplitude, and phase angles with respect to OLBNP are presented. AP was relatively well regulated as demonstrated by small oscillations in half amplitude (3.5 mmHg) that were independent of OLBNP frequency and similar to unstressed control spectra. Due to the biomechanics of the system, the magnitudes of oscillations in calf circumference (CC) and CVP decreased with increasing frequency; therefore, we normalized responses by these indexes of the fluid volume shifted. The ratios of oscillations in AP to oscillations in CC increased by an order of magnitude, whereas oscillations in CVP to oscillations in CC and oscillations in AP to oscillations in CVP both tripled between 0.004 and 0.1 Hz. Therefore, even though the amount of fluid shifted by OLBNP decreased with increasing frequency, the magnitude of both CVP and AP oscillations per volume of fluid shifted increased (peaking at 0.08 Hz). The phase relationships between variables, particularly the increasing lags in SV and TPR, but not CVP, indicated that efferent responses with lags of 5-6 s could account for the observed responses. We conclude that, at frequencies below 0.02 Hz, the neural system of humans functioned optimally in regulating AP; OLBNP-induced decreases in SV (by as much as 50%) were counteracted by appropriate oscillations in HR and TPR responses. As OLBNP frequency increased, SV, TPR, and HR oscillations increasingly lagged the input and became less optimally timed for AP regulation.

  4. Human Memory CD4+ T Cell Immune Responses against Giardia lamblia.

    Science.gov (United States)

    Saghaug, Christina Skår; Sørnes, Steinar; Peirasmaki, Dimitra; Svärd, Staffan; Langeland, Nina; Hanevik, Kurt

    2015-09-16

    The intestinal protozoan parasite Giardia lamblia may cause severe prolonged diarrheal disease or pass unnoticed as an asymptomatic infection. T cells seem to play an important role in the immune response to Giardia infection, and memory responses may last years. Recently, TH17 responses have been found in three animal studies of Giardia infection. The aim of this study was to characterize the human CD4(+) T cell responses to Giardia. Peripheral blood mononuclear cells (PBMCs) were obtained from 21 returning travelers with recent or ongoing giardiasis and 12 low-risk healthy controls and stimulated in vitro with Giardia lamblia proteins. Production of tumor necrosis factor alpha (TNF-α), gamma interferon, interleukin-17A (IL-17A), IL-10, and IL-4 was measured in CD4(+) effector memory (EM) T cells after 24 h by flow cytometry. After 6 days of culture, activation and proliferation were measured by flow cytometry, while an array of inflammatory cytokine levels in supernatants were measured with multiplex assays. We found the number of IL-17A-producing CD4(+) EM T cells, as well as that of cells simultaneously producing both IL-17A and TNF-α, to be significantly elevated in the Giardia-exposed individuals after 24 h of antigen stimulation. In supernatants of PBMCs stimulated with Giardia antigens for 6 days, we found inflammation-associated cytokines, including 1L-17A, as well as CD4(+) T cell activation and proliferation, to be significantly elevated in the Giardia-exposed individuals. We conclude that symptomatic Giardia infection in humans induces a CD4(+) EM T cell response of which IL-17A production seems to be an important component. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Identification of functional hypoxia inducible factor response elements in the human lysyl oxidase gene promoter.

    Science.gov (United States)

    Wang, Victoria; Davis, David A; Yarchoan, Robert

    2017-08-19

    Human lysyl oxidase (LOX) is a hypoxia-responsive gene whose product catalyzes collagen crosslinking and is thought to be important in cancer metastasis and osteoarthritis. We previously demonstrated that LOX was upregulated by hypoxia inducible factor 2 (HIF-2) more strongly than hypoxia inducible 1 (HIF-1). Here, we further investigated the response of the LOX gene and LOX promoter to HIFs. LOX mRNA, measured by real time reverse transcriptase-PCR, was strongly up-regulated (almost 40-fold), by transfection of HEK-293T cells with a plasmid encoding the HIF-2α subunit of HIF-2, but only three-fold by a plasmid encoding HIF-1α. LOX protein was detectable by Western blot of cells transfected with HIF-2α, but not with HIF-1α. Analysis of a 1487 bp promoter sequence upstream of the human LOX gene revealed 9 potential hypoxia response elements (HREs). Promoter truncation allowed the mapping of two previously unidentified functional HREs, called here HRE8 and HRE7; -455 to -451 and -382 to -386 bp, respectively, upstream of the start codon for LOX. Removal or mutation of these HREs led to a substantial reduction in both HIF-1α and HIF-2α responsiveness. Also, expression of LOX was significantly inhibited by a small molecule specific HIF-2 inhibitor. In conclusion, LOX is highly responsive to HIF-2α and this is largely mediated by two previously unidentified HREs. These observations enhance our understanding of the regulation of this important gene involved in cancer and osteoarthritis, and suggest that these conditions may be targeted by HIF-2 inhibitors. Published by Elsevier Inc.

  6. Human Memory CD4+ T Cell Immune Responses against Giardia lamblia

    Science.gov (United States)

    Sørnes, Steinar; Peirasmaki, Dimitra; Svärd, Staffan; Langeland, Nina

    2015-01-01

    The intestinal protozoan parasite Giardia lamblia may cause severe prolonged diarrheal disease or pass unnoticed as an asymptomatic infection. T cells seem to play an important role in the immune response to Giardia infection, and memory responses may last years. Recently, TH17 responses have been found in three animal studies of Giardia infection. The aim of this study was to characterize the human CD4+ T cell responses to Giardia. Peripheral blood mononuclear cells (PBMCs) were obtained from 21 returning travelers with recent or ongoing giardiasis and 12 low-risk healthy controls and stimulated in vitro with Giardia lamblia proteins. Production of tumor necrosis factor alpha (TNF-α), gamma interferon, interleukin-17A (IL-17A), IL-10, and IL-4 was measured in CD4+ effector memory (EM) T cells after 24 h by flow cytometry. After 6 days of culture, activation and proliferation were measured by flow cytometry, while an array of inflammatory cytokine levels in supernatants were measured with multiplex assays. We found the number of IL-17A-producing CD4+ EM T cells, as well as that of cells simultaneously producing both IL-17A and TNF-α, to be significantly elevated in the Giardia-exposed individuals after 24 h of antigen stimulation. In supernatants of PBMCs stimulated with Giardia antigens for 6 days, we found inflammation-associated cytokines, including 1L-17A, as well as CD4+ T cell activation and proliferation, to be significantly elevated in the Giardia-exposed individuals. We conclude that symptomatic Giardia infection in humans induces a CD4+ EM T cell response of which IL-17A production seems to be an important component. PMID:26376930

  7. Class specific antibody responses to newborn larva antigens during Trichinella spiralis human infection

    Directory of Open Access Journals (Sweden)

    Mendez-Loredo B.

    2001-06-01

    Full Text Available A follow-up study of the class antibody responses to newborn larva (NBL antigens in individuals involved in an outbreak of human trichinellosis was carried out by ELISA assays. The data showed that similar kinetics of antibody responses of different magnitude developed in trichinellosis patients; it was low by week 3, a peak raised by week 5 and decreased from week 7 up to the end of the study. The IgA-ELISA assay was the most sensitive and specific while the IgM was the least sensitive and specific. IgA antibodies to NBL antigens were detected in 80 % of patients while IgE, IgG and IgM responses were observed in 44, 31 and 19 % of the patients by week 3, respectively. From weeks 5 to 7, IgA antibodies were found in 89 to 100 % of the patients while lower percentages (0-82 % were found for the other isotypes. Reactivity of IgA, IgE, IgG and IgM to NBL antigens decreased from week 37 to 57 after infection (0-38 %. These results suggest that detection of IgA antibodies may be useful for early diagnosis and epidemiological studies in human trichinellosis.

  8. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kazuyo [Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD (United States); Adhikari, Rewati [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); Yamada, Kenneth M. [National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Dhawan, Subhash, E-mail: subhash.dhawan@fda.hhs.gov [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2015-08-14

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection.

  9. Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques.

    Science.gov (United States)

    Grandin, Clément; Lucas-Hourani, Marianne; Clavel, Marine; Taborik, Fabrice; Vabret, Astrid; Tangy, Frédéric; Contamin, Hugues; Vidalain, Pierre-Olivier

    2015-04-01

    There is no large-scale therapy available against human respiratory syncytial virus (hRSV), a major pathogen responsible for acute respiratory diseases. Macaques represent an interesting animal model to evaluate potential treatments because of their genetic, anatomical and immunological proximity with humans. However, the parameters that influence hRSV growth and control in this model are still poorly understood. We have documented in the following study the influence of age as well as repeated infections on the virological, clinical and immunological parameters of this animal model. Following intranasal inoculation, hRSV replicated in the upper respiratory tract for less than 15 days with no clinical signs regardless of age. Interestingly, we observed the induction of a local immune response at the nasal mucosa as assessed by expression profiles of inflammatory and IFN-stimulated genes. Animals also developed specific antibodies and were immune to reinfection. Thus, we showed that even in infant macaques, intranasal hRSV infection induced both local and systemic immune responses to efficiently control the virus. © 2015 The Authors.

  10. Response of human dental pulp capped with biodentine and mineral trioxide aggregate.

    Science.gov (United States)

    Nowicka, Alicja; Lipski, Mariusz; Parafiniuk, Mirosław; Sporniak-Tutak, Katarzyna; Lichota, Damian; Kosierkiewicz, Anita; Kaczmarek, Wojciech; Buczkowska-Radlińska, Jadwiga

    2013-06-01

    Biodentine is a new bioactive cement that is similar to the widely used mineral trioxide aggregate (MTA). It has dentin-like mechanical properties, which may be considered a suitable material for clinical indications of dentin-pulp complex regeneration such as direct pulp capping. The purpose of the present study was to compare the response of the pulp-dentin complex in human teeth after direct capping with this new tricalcium silicate-based cement with that of MTA. Pulps in 28 caries-free maxillary and mandibular permanent intact human molars scheduled for extraction for orthodontic reasons were mechanically exposed and assigned to 1 of 2 experimental groups, Biodentine or MTA, and 1 control group. Assay of periapical response and clinical examination were performed. After 6 weeks, the teeth were extracted, stained with hematoxylin-eosin, and categorized by using a histologic scoring system. The majority of specimens showed complete dentinal bridge formation and an absence of inflammatory pulp response. Layers of well-arranged odontoblast and odontoblast-like cells were found to form tubular dentin under the osteodentin. Statistical analysis showed no significant differences between the Biodentine and MTA experimental groups during the observation period. Within the limitations of this study, Biodentine had a similar efficacy in the clinical setting and may be considered an interesting alternative to MTA in pulp-capping treatment during vital pulp therapy. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Aberrant response to commensal Bacteroides thetaiotaomicron in Crohn's disease: an ex vivo human organ culture study.

    Science.gov (United States)

    Edwards, L A; Lucas, M; Edwards, E A; Torrente, F; Heuschkel, R B; Klein, N J; Murch, S H; Bajaj-Elliott, M; Phillips, A D

    2011-05-01

    Human ex vivo evidence indicating that an inappropriate immune response(s) to nonpathogenic bacteria contributes to disease pathogenesis in pediatric Crohn's disease (CD) is limited. The aim of the present study was to compare and contrast the early innate immune response of pediatric "healthy" versus CD mucosa to pathogenic, probiotic, and commensal bacteria. "Healthy control" and CD pediatric mucosal biopsies (terminal ileum and transverse colon) were cocultured for 8 hours with E. coli O42, Lactobacillus GG (LGG), Bacteroidesthetaiotaomicron (B. theta), or stimulated with interleukin (IL)-1β (positive control). Matched nonstimulated biopsies served as experimental controls. IL-8 was the immune marker of choice. IL-8 mRNA and protein levels were quantified by quantitative polymerase chain reaction and sandwich enzyme-linked immunosorbent assay, respectively. IL-8 secretion was observed when control, ileal biopsies were exposed to pathogenic O42 and probiotic LGG, with no response noted to commensal B. theta. In comparison, Crohn's ileal biopsies showed impaired ability to induce IL-8 in response to O42 and LGG. Control colonic tissue showed a limited response to O42 or B. theta and LGG significantly reduced IL-8 secretion. Unlike control tissue, however, Crohn's ileal and colonic tissue did respond to B. theta, with more enhanced expression in the colon. We provide the first ex vivo data to support the notion that aberrant mucosal recognition of commensal bacteria may contribute to pediatric CD. While IL-8 responses to O42 and LGG varied with disease status and anatomical location, B. theta consistently induced significant IL-8 both in ileal and colonic CD tissue, which was not seen in control, healthy tissue. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

  12. Differential responses to x-irradiation of subpopulations of two heterogeneous human carcinomas in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Leith, J.T.; Dexter, D.L.; DeWyngaert, J.K.; Zeman, E.M.; Chu, M.Y.; Calabresi, P.; Glicksman, A.S.

    1982-07-01

    The responses of two heterogeneous human cancer cell lines and their derivative clones to graded single doses of X-rays were examined in vitro. One system consisted of the human colon carcinoma line DLD-1 and two subpopulations (clones A and D). The second system consisted of the human lung carcinoma line (LX1) and four subpopulations (LX1-1, LX1-2, LX1-3, and LX1-9). These subpopulations have previously been shown to be markedly heterogeneous in terms of such characteristics as karyotype, morphology, drug sensitivity, tumorigenicity, and expression of membrane glycoproteins (such as carcinoembryonic antigen and tumor colonic mucoprotein antigen). Exponentially growing cultures were irradiated with graded single doses of 100-kVp X-rays. Survival was assessed using colony formation as the end point, and responses from multiple experiments were fitted to the single-hit, multitarget equation of cell survival. Values for the mean lethal dose (D0, grays), quasithreshold dose (Dq, grays), and extrapolation number (n) were obtained. For the human colon adenocarcinoma system, these values for the three tumor lines were: DLD-1, 0.95, 2.34, and 11.7; clone A, 1.06, 2.23 and 8.20; and clone D, 1.08, 1.89, and 5.80. For the human lung carcinoma system, these values for the five sublines were: LX1, 1.14, 0.19, and 1.20; LX1-1, 0.96, 2.06, and 8.54; LX1-2, 0.98, 0.88, and 2.48; LX1-3, 0.68, 2.05, and 20.3; and LX1-9, 1.12, 0.00, and 1.00. These two human tumor systems therefore exhibit variability in their intrinsic sensitivity to X-irradiation. The data indicate that failure of some human carcinomas to respond to physical treatment modalities can be due to preexisting resistant subpopulations.

  13. Mechanical response of the herniated human abdomen to the placement of different prostheses.

    Science.gov (United States)

    Hernández-Gascón, Belén; Peña, Estefanía; Grasa, Jorge; Pascual, Gemma; Bellón, Juan M; Calvo, Begoña

    2013-05-01

    This paper describes a method designed to model the repaired herniated human abdomen just after surgery and examine its static mechanical response to the maximum intra-abdominal pressure provoked by a physiological movement (standing cough). The model is based on the real geometry of the human abdomen bearing a large incisional hernia with several anatomical structures differentiated by MRI. To analyze the outcome of hernia repair, the surgical procedure was simulated by modeling a prosthesis placed over the hernia. Three surgical meshes with different mechanical properties were considered: an isotropic heavy-weight mesh (Surgipro®), a slightly anisotropic light-weight mesh (Optilene®), and a highly anisotropic medium-weight mesh (Infinit®). Our findings confirm that anisotropic implants need to be positioned such that the most compliant axis of the mesh coincides with the craneo-caudal direction of the body.

  14. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    activation. Here, we show that, in a series of human colorectal adenomas, those with deregulation of cyclin D1 and/or p16(Ink4a) showed little evidence of constitutive DNA damage response (DDR), contrary to cyclin E-overexpressing higher-grade cases. These observations were consistent with diverse cell...... culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... cells, analogous to elevated cyclin E. These results highlight differential effect of diverse oncogenic events on driving the 'cancer cell cycles' and their ability to deregulate the replication-driving CDK2 kinase and to alarm the DDR as a potential anticancer barrier in accordance...

  15. A Hormone-responsive 3D Culture Model of the Human Mammary Gland Epithelium.

    Science.gov (United States)

    Speroni, Lucia; Sweeney, Michael F; Sonnenschein, Carlos; Soto, Ana M

    2016-02-07

    The process of mammary epithelial morphogenesis is influenced by hormones. The study of hormone action on the breast epithelium using 2D cultures is limited to cell proliferation and gene expression endpoints. However, in the organism, mammary morphogenesis occurs in a 3D environment. 3D culture systems help bridge the gap between monolayer cell culture (2D) and the complexity of the organism. Herein, we describe a 3D culture model of the human breast epithelium that is suitable to study hormone action. It uses the commercially available hormone-responsive human breast epithelial cell line, T47D, and rat tail collagen type 1 as a matrix. This 3D culture model responds to the main mammotropic hormones: estradiol, progestins and prolactin. The influence of these hormones on epithelial morphogenesis can be observed after 1- or 2-week treatment according to the endpoint. The 3D cultures can be harvested for analysis of epithelial morphogenesis, cell proliferation and gene expression.

  16. Distinct human antibody response to the biological warfare agent Burkholderia mallei.

    Science.gov (United States)

    Varga, John J; Vigil, Adam; DeShazer, David; Waag, David M; Felgner, Philip; Goldberg, Joanna B

    2012-10-01

    The genetic similarity between Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. In 2000, the first human case of glanders in North America since 1945 was reported in a microbiology laboratory worker. Leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohort of melioidosis patients in southeast Asia, we describe the antibody response in a human with glanders. Analysis of 156 peptides present on the array revealed antibodies against 17 peptides with a > 2-fold increase in this infection. Unexpectedly, when the glanders data were compared with a previous data set from B. pseudomallei infections, there were only two highly increased antibodies shared between these two infections. These findings have implications in the diagnosis and treatment of B. mallei and B. pseudomallei infections.

  17. On the long-latency reflex responses of the human flexor digitorum profundus.

    Science.gov (United States)

    Matthews, P B; Miles, T S

    1988-10-01

    1. Electromyography (surface and intramuscular) has been used to study the reflex responses of the human flexor digitorum profundus (FDP) to angular rotation of the distal interphalangeal joint of the 4th finger. This has been done with the hand in three separate positions which, owing to the arrangement of the various tendons, allow the movement to be transmitted to (a) both the flexor and extensor muscles, (b) FDP alone (extensors disengaged) and (c) neither flexor nor extensor muscles (all muscles disengaged, but cutaneous and joint receptors still potentially activated). The stimuli were applied while the subject was voluntarily contracting FDP to produce a constant level of EMG activity; this remained possible when the muscle was disengaged from the joint. 2. With all muscles connected, FDP behaved similarly to the analogous long flexor of the thumb. 'Stretch' elicited a prolonged complex response starting with a short-latency component corresponding to the tendon jerk. Unloading of the contracting muscle caused a pronounced reduction of its on-going EMG activity. The latency of this latter effect was approximately 20 ms greater than that of the initial stretch-evoked response, thereby demonstrating that it was not due to a disfacilitation via the short-latency pathway (on reduction of the tonic spindle afferent firing from FDP as it shortened). 3. With all muscles disengaged, movement of the joint in either direction evoked simply a weak, variable excitatory response, with a latency somewhat greater than that of the normal unloading response. This was attributed to the activation of cutaneous and/or joint receptors. The effectiveness of the disengagement of the flexor was demonstrated by the abolition of its normal stretch-evoked short-latency response. 4. With the flexor engaged and the extensors disengaged both stretch and release evoked their normal types of response. In control experiments, surface EMG recordings from the interosseus muscles confirmed

  18. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

    Directory of Open Access Journals (Sweden)

    Eaton John W

    2007-07-01

    Full Text Available Abstract Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing plasma or (fibrinogen-free serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior

  19. Mild metabolic acidosis impairs the β-adrenergic response in isolated human failing myocardium.

    Science.gov (United States)

    Schotola, Hanna; Toischer, Karl; Popov, Aron F; Renner, André; Schmitto, Jan D; Gummert, Jan; Quintel, Michael; Bauer, Martin; Maier, Lars S; Sossalla, Samuel

    2012-08-13

    Pronounced extracellular acidosis reduces both cardiac contractility and the β-adrenergic response. In the past, this was shown in some studies using animal models. However, few data exist regarding how the human end-stage failing myocardium, in which compensatory mechanisms are exhausted, reacts to acute mild metabolic acidosis. The aim of this study was to investigate the effect of mild metabolic acidosis on contractility and the β-adrenergic response of isolated trabeculae from human end-stage failing hearts. Intact isometrically twitching trabeculae isolated from patients with end-stage heart failure were exposed to mild metabolic acidosis (pH 7.20). Trabeculae were stimulated at increasing frequencies and finally exposed to increasing concentrations of isoproterenol (0 to 1 × 10(-6) M). A mild metabolic acidosis caused a depression in twitch-force amplitude of 26% (12.1 ± 1.9 to 9.0 ± 1.5 mN/mm(2); n = 12; P acidosis group, with an EC50 of 5.834 × 10(-8) M (confidence interval (CI), 3.48 × 10(-8) to 9.779 × 10(-8); n = 9), compared with the control group, which had an EC50 of 1.056 × 10(-8) M (CI, 2.626 × 10(-9) to 4.243 × 10(-8); n = 10; P metabolic acidosis reduces cardiac contractility and significantly impairs the β-adrenergic force response in human failing myocardium. Thus, our results could contribute to the still-controversial discussion about the therapy regimen of acidosis in patients with critical heart failure.

  20. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

    Science.gov (United States)

    Zdolsek, Johann; Eaton, John W; Tang, Liping

    2007-01-01

    Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age) were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing) plasma or (fibrinogen-free) serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior to, and shortly after

  1. Molecular genetics of human immune responsiveness to Lolium perenne (rye) allergen, Lol p III.

    Science.gov (United States)

    Ansari, A A; Freidhoff, L R; Marsh, D G

    1989-01-01

    Lol p II and III are each about 11-kD protein allergens from the pollen of Lolium perenne (rye grass). We have found that human immune responses (IgE and IgG antibodies) to both proteins are significantly associated with HLA-DR3. In addition, the two proteins are cross-reactive with the antibodies in many human sera (about 84% human sera showed the cross-reactivity). We have determined greater than 90% of the amino acid sequences of the two proteins and found that they are at least 54% homologous. Berzofsky found that 75% of the 23 known T cell sites in various proteins had an amphipathic structure. Our analysis by the same method showed that both Lol p II and III have a major region of amphipathicity (at residues 61-67, Lol p III numbering) which might contain sites for binding to an Ia molecule and a T cell receptor. This region is identical between Lol p II and III, except for an Arg-Lys substitution, and could account, in part, for the DR3 association with responsiveness to both molecules. An interesting difference between the two proteins is that immune response to Lol p III is associated with DR5 (in addition to DR3), whereas no DR5 association is found in the case of Lol p II. One possibility is that Lol p III has an additional site which binds to the DR5 Ia molecule. Lol p III indeed has a second highly amphiphathic peptide, 24-30 (Lol p III 24 R P G D T L A 30), which is different and not amphipathic in Lol p II.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Effect of training and familiarity on responsiveness to human cues in domestic dogs (Canis familiaris).

    Science.gov (United States)

    Cunningham, Clare L; Ramos, Mari F

    2014-05-01

    Domestic dogs (Canis familiaris) seem to possess an evolved competency to follow human-given cues, often out-performing their wild progenitor the wolf (Canis lupus) on cue-following tasks. However, domestication may not be solely responsible for the socio-cognitive skills of dogs, with ontogenetic experience also playing a role. This research evaluated the effects of intensive training on cue-following behaviour using an unreinforced object-choice paradigm. The responses of dogs that were trained to competitive levels were compared to those of pet dogs with only basic training, and dogs living in an animal shelter that demonstrated no or only rudimentary following of basic commands. Using a cue-following task where three types of cues were presented by familiar and unfamiliar human partners, the number of cues followed by each training group were recorded. All dogs found cues where gesture was combined with a congruent head and eye movement easier to follow than either gesture or eye gaze alone. Whether the cue-giver was familiar or not had a significant effect on number of cues followed in homed dogs, and the performance of shelter dogs was comparable to the other groups when faced with an unfamiliar cue-giver. Contrary to predictions, level of training did not improve performance on the cue-following task. This work does provide support for the presence of an evolved adaptation to exploit social cues provided by humans that can be augmented by familiarity with the cue giver. However, additional joint activity as experienced in an intensive training regime does not seem to increase accuracy in following human-given cues.

  3. Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

    Science.gov (United States)

    Connolly, Adam; Robson, Matthew D.; Schneider, Jürgen; Burton, Rebecca; Plank, Gernot; Bishop, Martin J.

    2017-09-01

    Novel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic. In this study, we sought to investigate how electric fields from implanted devices interact with the highly trabeculated human endocardial surface to better understand shock success in order to help optimise future clinical protocols. A bi-ventricular human computational model was constructed from high resolution (350 μm) ex-vivo MR data, including anatomically accurate endocardial structures. Monophasic shocks were applied between a basal right ventricular catheter and an exterior ground. Shocks of varying strengths were applied with both anodal [positive right ventricle (RV) electrode] and cathodal (negative RV electrode) polarities at different states of tissue refractoriness and during induced arrhythmias. Anodal shocks induced isolated positive VEs at the distal side of "detached" trabeculations, which rapidly spread into hyperpolarised tissue on the surrounding endocardial surfaces following the shock. Anodal shocks thus depolarised more tissue 10 ms after the shock than cathodal shocks where the propagation of activation from VEs induced on the proximal side of "detached" trabeculations was prevented due to refractory endocardium. Anodal shocks increased arrhythmia complexity more than cathodal shocks during failed anti-arrhythmia shocks. In conclusion, multiple detached

  4. Analyzing the EU Refugee Crisis: Humanity, Heritage and Responsibility to Protect

    Directory of Open Access Journals (Sweden)

    Amelia Hadfield

    2015-11-01

    Full Text Available 2015 has shaken the EU to its core. Hard upon the heels of geopolitical upheavals in Ukraine, as well as internal battles to define both Eurozone and energy governance, the refugee crisis has prompted a sober reckoning of the EU’s competence and its humanity. With an increasing number of articles and Special Issues in Politics and Governance focusing upon key aspects of the EU as both a political actor, and a source of governance, our autumn 2015 editorial looks briefly at the significance of the refugee crisis in the context of the EU’s current response and future options.

  5. Human Plasmacytoid Dendritic Cells Elicited Different Responses after Infection with Pathogenic and Nonpathogenic Junin Virus Strains.

    Science.gov (United States)

    Negrotto, Soledad; Mena, Hebe A; Ure, Agustin E; Jaquenod De Giusti, Carolina; Bollati-Fogolín, Mariela; Vermeulen, Elba M; Schattner, Mirta; Gómez, Ricardo M

    2015-07-01

    The arenavirus Junin virus (JUNV) is the etiologic agent of Argentine hemorrhagic fever. We characterized the JUNV infection of human peripheral blood-derived plasmacytoid dendritic cells (hpDC), demonstrating that hpDC are susceptible to infection with the C#1 strain (attenuated) and even more susceptible to infection with the P (virulent) JUNV strain. However, hpDC elicited different responses in terms of viability, activation, maturation, and cytokine expression after infection with both JUNV strains. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Responses of Human Medial Temporal Lobe Neurons Are Modulated by Stimulus Repetition

    Science.gov (United States)

    Pedreira, Carlos; Mormann, Florian; Kraskov, Alexander; Cerf, Moran; Fried, Itzhak; Koch, Christof

    2010-01-01

    Recent studies have reported the presence of single neurons with strong responses to visual inputs in the human medial temporal lobe. Here we show how repeated stimulus presentation—photos of celebrities and familiar individuals, landmark buildings, animals, and objects—modulates the firing rate of these cells: a consistent decrease in the neural activity was registered as images were repeatedly shown during experimental sessions. The effect of repeated stimulus presentation was not the same for all medial temporal lobe areas. These findings are consistent with the view that medial temporal lobe neurons link visual percepts to declarative memory. PMID:19864436

  7. In vivo biological response to extracorporeal shockwave therapy in human tendinopathy

    DEFF Research Database (Denmark)

    Waugh, C. M.; Morrissey, D.; Jones, E.

    2015-01-01

    Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session......-responders based on a minimum 5-fold increase in any inflammatory marker or MMP from pre- to post-ESWT. Our findings provide novel evidence of the biological mechanisms underpinning ESWT in humans in vivo. They suggest that the mechanical stimulus provided by ESWT might aid tendon remodelling in tendinopathy...

  8. Differential Antagonism of Human Innate Immune Responses by Tick-Borne Phlebovirus Nonstructural Proteins.

    Science.gov (United States)

    Rezelj, Veronica V; Li, Ping; Chaudhary, Vidyanath; Elliott, Richard M; Jin, Dong-Yan; Brennan, Benjamin

    2017-01-01

    In recent years, several newly discovered tick-borne viruses causing a wide spectrum of diseases in humans have been ascribed to the Phlebovirus genus of the Bunyaviridae family. The nonstructural protein (NSs) of bunyaviruses is the main virulence factor and interferon (IFN) antagonist. We studied the molecular mechanisms of IFN antagonism employed by the NSs proteins of human apathogenic Uukuniemi virus (UUKV) and those of Heartland virus (HRTV) and severe fever with thrombocytopenia syndrome virus (SFTSV), both of which cause severe disease. Using reporter assays, we found that UUKV NSs weakly inhibited the activation of the beta interferon (IFN-β) promoter and response elements. UUKV NSs weakly antagonized human IFN-β promoter activation through a novel interaction with mitochondrial antiviral-signaling protein (MAVS), confirmed by coimmunoprecipitation and confocal microscopy studies. HRTV NSs efficiently antagonized both IFN-β promoter activation and type I IFN signaling pathways through interactions with TBK1, preventing its phosphorylation. HRTV NSs exhibited diffused cytoplasmic localization. This is in comparison to the inclusion bodies formed by SFTSV NSs. HRTV NSs also efficiently interacted with STAT2 and impaired IFN-β-induced phosphorylation but did not affect STAT1 or its translocation to the nucleus. Our results suggest that a weak interaction between STAT1 and HRTV or SFTSV NSs may explain their inability to block type II IFN signaling efficiently, thus enabling the activation of proinflammatory responses that lead to severe disease. Our findings offer insights into how pathogenicity may be linked to the capacity of NSs proteins to block the innate immune system and illustrate the plethora of viral immune evasion strategies utilized by emerging phleboviruses. IMPORTANCE Since 2011, there has been a large expansion in the number of emerging tick-borne viruses that have been assigned to the Phlebovirus genus. Heartland virus (HRTV) and SFTS

  9. The Genetic Influences on Oxycodone Response Characteristics in Human Experimental Pain

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Sato, Hiroe; Nielsen, Lecia Møller

    2015-01-01

    Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response...... PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P ... to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral...

  10. Effects of d-Amphetamine and Haloperidol on Modulation of the Human Acoustic Startle Response

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    Hossein Kaviani

    2006-04-01

    Full Text Available "nObjective:This study aimed to examine the effects of haloperidol and amphetamine on human startle response modulated by emotionally-toned film clips. "n "n Method:Sixty participants, in two groups (one receiving haloperidol and the other receiving amphetamine were tested using electromyography (EMG to measure eye-blink muscle (orbicular oculi while different emotions were induced by six 2-minute film clips. Results:An affective rating shows the negative and positive effects of the two drugs on emotional reactivity, neither amphetamine nor haloperidol had any impact on the modulation of the startle response. Conclusion: The methodological and theoretical aspects of the study and findings will be discussed.

  11. Interplay between Human Cytomegalovirus and Intrinsic/Innate Host Responses: A Complex Bidirectional Relationship

    Science.gov (United States)

    Rossini, Giada; Cerboni, Cristina; Santoni, Angela; Landini, Maria Paola; Landolfo, Santo; Gatti, Deborah; Gribaudo, Giorgio; Varani, Stefania

    2012-01-01

    The interaction between human cytomegalovirus (HCMV) and its host is a complex process that begins with viral attachment and entry into host cells, culminating in the development of a specific adaptive response that clears the acute infection but fails to eradicate HCMV. We review the viral and cellular partners that mediate early host responses to HCMV with regard to the interaction between structural components of virions (viral glycoproteins) and cellular receptors (attachment/entry receptors, toll-like receptors, and other nucleic acid sensors) or intrinsic factors (PML, hDaxx, Sp100, viperin, interferon inducible protein 16), the reactions of innate immune cells (antigen presenting cells and natural killer cells), the numerous mechanisms of viral immunoevasion, and the potential exploitation of events that are associated with early phases of virus-host interplay as a therapeutic strategy. PMID:22701276

  12. Response of isolated muscle of the human cervix to electrofield stimulation.

    Science.gov (United States)

    Bryman, I; Lindblom, B; Norström, A

    1988-01-01

    Contractile activity was registered isometrically in isolated strip biopsies from the uterine cervix of nonpregnant, early pregnant and term pregnant women, and the influence of electrofield stimulation (EFS) was studied. In the great majority of women an excitatory effect was observed, but occasionally an inhibitory response occurred. The excitatory effect of EFS was reduced and, in many cases, changed to inhibition during treatment with guanethidine and phenoxybenzamine. These inhibitory effects were not antagonized by treatment with propranolol, indicating that the responses were not mediated by beta-adrenoceptors. Tetrodotoxin reduced or abolished the excitatory effect of EFS. The data suggest that contractile activity of the human cervix is influenced by both adrenergic and nonadrenergic neurons, which remain intact throughout pregnancy. This innervation may be a central part of neuromuscular control systems which undergo important adaptive changes during pregnancy and in connection with parturition.

  13. Galactomannan Downregulates the Inflammation Responses in Human Macrophages via NFκB2/p100

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    Víctor Toledano

    2015-01-01

    Full Text Available We show that galactomannan, a polysaccharide consisting of a mannose backbone with galactose side groups present on the cell wall of several fungi, induces a reprogramming of the inflammatory response in human macrophages through dectin-1 receptor. The nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NFκB2/p100 was overexpressed after galactomannan challenge. Knocking down NFκB2/p100 using small interfering RNA (siRNA indicated that NFκB2/p100 expression is a crucial factor in the progression of the galactomannan-induced refractoriness. The data presented in this study could be used as a modulator of inflammatory response in clinical situations where refractory state is required.

  14. Effect of Losartan on the Acute Response of Human Elderly Skeletal Muscle to Exercise

    DEFF Research Database (Denmark)

    Heisterberg, Mette Flindt; Andersen, Jesper L; Schjerling, Peter

    2017-01-01

    PURPOSE: To investigate the effect of blocking the angiotensin II type I receptor (AT1R) upon the response to acute heavy resistance exercise in elderly human skeletal muscle. The hypothesis was that AT1R blocking would result in a superior myogenic response accompanied by downregulation of TGF......-β and upregulation of IGF-1 signalling. METHODS: 28 healthy elderly men (+64 years) were randomized into two groups, consuming either AT1R blocker (Losartan, 100mg/day) or Placebo for 18 days prior to exercise. Participants performed one bout of heavy unilateral resistance exercise. Six muscle biopsies were obtained...... from the vastus lateralis muscles of each subject: two before exercise, and four after exercise (4.5 hours and 1, 4 and 7 days). Blood pressure and blood samples were collected at the same time points. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells...

  15. Immune Response to Human Metapneumovirus Infection: What We Have Learned from the Mouse Model

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    Nagarjuna R. Cheemarla

    2015-09-01

    Full Text Available Human Metapneumovirus (hMPV is a leading respiratory viral pathogen associated with bronchiolitis, pneumonia, and asthma exacerbation in young children, the elderly and immunocompromised individuals. The development of a potential vaccine against hMPV requires detailed understanding of the host immune system, which plays a significant role in hMPV pathogenesis, susceptibility and vaccine efficacy. As a result, animal models have been developed to better understand the mechanisms by which hMPV causes disease. Several animal models have been evaluated and established so far to study the host immune responses and pathophysiology of hMPV infection. However, inbred laboratory mouse strains have been one of the most used animal species for experimental modeling and therefore used for the studies of immunity and immunopathogenesis to hMPV. This review summarizes the contributions of the mouse model to our understanding of the immune response against hMPV infection.

  16. Premature infants have impaired airway antiviral IFNγ responses to human metapneumovirus compared to respiratory syncytial virus.

    Science.gov (United States)

    Pancham, Krishna; Perez, Geovanny F; Huseni, Shehlanoor; Jain, Amisha; Kurdi, Bassem; Rodriguez-Martinez, Carlos E; Preciado, Diego; Rose, Mary C; Nino, Gustavo

    2015-10-01

    It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. Nasal airway secretions were collected from 140 children ≤ 3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (respiratory disease in children with history of prematurity.

  17. Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans

    DEFF Research Database (Denmark)

    Astrup, A; Andersen, T; Christensen, N J

    1990-01-01

    in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose......A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower...... was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may...

  18. Phenotypic and functional characterization of human memory T cell responses to Burkholderia pseudomallei.

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    Patcharaporn Tippayawat

    Full Text Available Infection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas. In animal models, production of interferon-gamma (IFN-gamma is critical for resistance, but in humans the characteristics of IFN-gamma production and the bacterial antigens that are recognized by the cell-mediated immune response have not been defined.Peripheral blood from 133 healthy individuals who lived in the endemic area and had no history of melioidosis, 60 patients who had recovered from melioidosis, and 31 other patient control subjects were stimulated by whole bacteria or purified bacterial proteins in vitro, and IFN-gamma responses were analyzed by ELISPOT and flow cytometry.B. pseudomallei was a potent activator of human peripheral blood NK cells for innate production of IFN-gamma. In addition, healthy individuals with serological evidence of exposure to B. pseudomallei and patients recovered from active melioidosis developed CD4(+ (and CD8(+ T cells that recognized whole bacteria and purified proteins LolC, OppA, and PotF, members of the B. pseudomallei ABC transporter family. This response was primarily mediated by terminally differentiated T cells of the effector-memory (T(EMRA phenotype and correlated with the titer of anti-B. pseudomallei antibodies in the serum.Individuals living in a melioidosis-endemic region show clear evidence of T cell priming for the ability to make IFN-gamma that correlates with their serological status. The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide-conjugate subunit vaccines against this important but neglected disease.

  19. Mode-locking neurodynamics predict human auditory brainstem responses to musical intervals.

    Science.gov (United States)

    Lerud, Karl D; Almonte, Felix V; Kim, Ji Chul; Large, Edward W

    2014-02-01

    The auditory nervous system is highly nonlinear. Some nonlinear responses arise through active processes in the cochlea, while others may arise in neural populations of the cochlear nucleus, inferior colliculus and higher auditory areas. In humans, auditory brainstem recordings reveal nonlinear population responses to combinations of pure tones, and to musical intervals composed of complex tones. Yet the biophysical origin of central auditory nonlinearities, their signal processing properties, and their relationship to auditory perception remain largely unknown. Both stimulus components and nonlinear resonances are well represented in auditory brainstem nuclei due to neural phase-locking. Recently mode-locking, a generalization of phase-locking that implies an intrinsically nonlinear processing of sound, has been observed in mammalian auditory brainstem nuclei. Here we show that a canonical model of mode-locked neural oscillation predicts the complex nonlinear population responses to musical intervals that have been observed in the human brainstem. The model makes predictions about auditory signal processing and perception that are different from traditional delay-based models, and may provide insight into the nature of auditory population responses. We anticipate that the application of dynamical systems analysis will provide the starting point for generic models of auditory population dynamics, and lead to a deeper understanding of nonlinear auditory signal processing possibly arising in excitatory-inhibitory networks of the central auditory nervous system. This approach has the potential to link neural dynamics with the perception of pitch, music, and speech, and lead to dynamical models of auditory system development. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells

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    Molenaar Douwe

    2010-11-01

    Full Text Available Abstract Background Modulation of the immune system is one of the most plausible mechanisms underlying the beneficial effects of probiotic bacteria on human health. Presently, the specific probiotic cell products responsible for immunomodulation are largely unknown. In this study, the genetic and phenotypic diversity of strains of the Lactobacillus plantarum species were investigated to identify genes of L. plantarum with the potential to influence the amounts of cytokines interleukin 10 (IL-10 and IL-12 and the ratio of IL-10/IL-12 produced by peripheral blood mononuclear cells (PBMCs. Results A total of 42 Lactobacillus plantarum strains isolated from diverse environmental and human sources were evaluated for their capacity to stimulate cytokine production in PBMCs. The L. plantarum strains induced the secretion of the anti-inflammatory cytokine IL-10 over an average 14-fold range and secretion of the pro-inflammatory cytokine IL-12 over an average 16-fold range. Comparisons of the strain-specific cytokine responses of PBMCs to comparative genome hybridization profiles obtained with L. plantarum WCFS1 DNA microarrays (also termed gene-trait matching resulted in the identification of 6 candidate genetic loci with immunomodulatory capacities. These loci included genes encoding an N-acetyl-glucosamine/galactosamine phosphotransferase system, the LamBDCA quorum sensing system, and components of the plantaricin (bacteriocin biosynthesis and transport pathway. Deletion of these genes in L. plantarum WCFS1 resulted in growth phase-dependent changes in the PBMC IL-10 and IL-12 cytokine profiles compared with wild-type cells. Conclusions The altered PBMC cytokine profiles obtained with the L. plantarum WCFS1 mutants were in good agreement with the predictions made by gene-trait matching for the 42 L. plantarum strains. This study therefore resulted in the identification of genes present in certain strains of L. plantarum which might be responsible for

  1. Phenotypic and functional characterization of human memory T cell responses to Burkholderia pseudomallei.

    Science.gov (United States)

    Tippayawat, Patcharaporn; Saenwongsa, Wipawee; Mahawantung, Jirawan; Suwannasaen, Duangchan; Chetchotisakd, Ploenchan; Limmathurotsakul, Direk; Peacock, Sharon J; Felgner, Philip L; Atkins, Helen S; Titball, Richard W; Bancroft, Gregory J; Lertmemongkolchai, Ganjana

    2009-01-01

    Infection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas. In animal models, production of interferon-gamma (IFN-gamma) is critical for resistance, but in humans the characteristics of IFN-gamma production and the bacterial antigens that are recognized by the cell-mediated immune response have not been defined. Peripheral blood from 133 healthy individuals who lived in the endemic area and had no history of melioidosis, 60 patients who had recovered from melioidosis, and 31 other patient control subjects were stimulated by whole bacteria or purified bacterial proteins in vitro, and IFN-gamma responses were analyzed by ELISPOT and flow cytometry. B. pseudomallei was a potent activator of human peripheral blood NK cells for innate production of IFN-gamma. In addition, healthy individuals with serological evidence of exposure to B. pseudomallei and patients recovered from active melioidosis developed CD4(+) (and CD8(+)) T cells that recognized whole bacteria and purified proteins LolC, OppA, and PotF, members of the B. pseudomallei ABC transporter family. This response was primarily mediated by terminally differentiated T cells of the effector-memory (T(EMRA)) phenotype and correlated with the titer of anti-B. pseudomallei antibodies in the serum. Individuals living in a melioidosis-endemic region show clear evidence of T cell priming for the ability to make IFN-gamma that correlates with their serological status. The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide-conjugate subunit vaccines against this important but neglected disease.

  2. Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Ying; Zhang, Ningzhe; Ellerby, Lisa M.; Davalos, Albert R.; Zeng, Xianmin; Campisi, Judith [Buck Institute for Research on Aging, Novato, CA 94945 (United States); Desprez, Pierre-Yves, E-mail: pydesprez@cpmcri.org [Buck Institute for Research on Aging, Novato, CA 94945 (United States); California Pacific Medical Center, Research Institute, San Francisco, CA 94107 (United States)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer hESCs and their progeny, NSCs and neurons, were exposed to ionizing radiation. Black-Right-Pointing-Pointer Upon irradiation, most hESCs died within 5-7 h. Black-Right-Pointing-Pointer Surviving NSCs underwent senescence and displayed features of astrocytes. Black-Right-Pointing-Pointer Surviving NSCs did not display the secretory phenotype expressed by pure astrocytes. Black-Right-Pointing-Pointer This study is to better understand the stress-responses of hESCs and their progeny. -- Abstract: Human embryonic stem cells (hESCs) hold promise for the treatment of many human pathologies. For example, hESCs and the neuronal stem cells (NSCs) and neurons derived from them have significant potential as transplantation therapies for a variety of neurodegenerative diseases. Two concerns about the use of hESCs and their differentiated derivatives are their ability to function and their ability to resist neoplastic transformation in response to stresses that inevitably arise during their preparation for transplantation. To begin to understand how these cells handle genotoxic stress, we examined the responses of hESCs and derived NSCs and neurons to ionizing radiation (IR). Undifferentiated hESCs were extremely sensitive to IR, with nearly all the cells undergoing cell death within 5-7 h. NSCs and neurons were substantially more resistant to IR, with neurons showing the most resistant. Of interest, NSCs that survived IR underwent cellular senescence and acquired astrocytic characteristics. Unlike IR-treated astrocytes, however, the NSC-derived astrocytic cells that survived IR did not display the typical pro-inflammatory, pro-carcinogenic senescence-associated secretory phenotype. These findings suggest distinct genotoxic stress-responses of hESCs and derived NSC and neuronal populations, and suggest that damaged NSCs, while failing to function, may not cause local inflammation.

  3. Bayesian approach to model CD137 signaling in human M. tuberculosis in vitro responses.

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    Darío A Fernández Do Porto

    Full Text Available Immune responses are qualitatively and quantitatively influenced by a complex network of receptor-ligand interactions. Among them, the CD137:CD137L pathway is known to modulate innate and adaptive human responses against Mycobacterium tuberculosis. However, the underlying mechanisms of this regulation remain unclear. In this work, we developed a Bayesian Computational Model (BCM of in vitro CD137 signaling, devised to fit previously gathered experimental data. The BCM is fed with the data and the prior distribution of the model parameters and it returns their posterior distribution and the model evidence, which allows comparing alternative signaling mechanisms. The BCM uses a coupled system of non-linear differential equations to describe the dynamics of Antigen Presenting Cells, Natural Killer and T Cells together with the interpheron (IFN-γ and tumor necrosis factor (TNF-α levels in the media culture. Fast and complete mixing of the media is assumed. The prior distribution of the parameters that describe the dynamics of the immunological response was obtained from the literature and theoretical considerations Our BCM applies successively the Levenberg-Marquardt algorithm to find the maximum a posteriori likelihood (MAP; the Metropolis Markov Chain Monte Carlo method to approximate the posterior distribution of the parameters and Thermodynamic Integration to calculate the evidence of alternative hypothesis. Bayes factors provided decisive evidence favoring direct CD137 signaling on T cells. Moreover, the posterior distribution of the parameters that describe the CD137 signaling showed that the regulation of IFN-γ levels is based more on T cells survival than on direct induction. Furthermore, the mechanisms that account for the effect of CD137 signaling on TNF-α production were based on a decrease of TNF-α production by APC and, perhaps, on the increase in APC apoptosis. BCM proved to be a useful tool to gain insight on the mechanisms of CD

  4. Extinction of Conditioned Responses to Methamphetamine-Associated Stimuli in Healthy Humans.

    Science.gov (United States)

    Cavallo, Joel S; Ruiz, Nicholas A; de Wit, Harriet

    2016-07-01

    Contextual stimuli present during drug experiences become associated with the drug through Pavlovian conditioning and are thought to sustain drug-seeking behavior. Thus, extinction of conditioned responses is an important target for treatment. To date, acquisition and extinction to drug-paired cues have been studied in animal models or drug-dependent individuals, but rarely in non-drug users. We have recently developed a procedure to study acquisition of conditioned responses after single doses of methamphetamine (MA) in healthy volunteers. Here, we examined extinction of these responses and their persistence after conditioning. Healthy adults (18-35 years; N = 20) received two pairings of audio-visual stimuli with MA (20 mg oral) or placebo. Responses to stimuli were assessed before and after conditioning, using three tasks: behavioral preference, attentional bias, and subjective "liking." Subjects exhibited behavioral preference for the drug-paired stimuli at the first post-conditioning test, but this declined rapidly on subsequent extinction tests. They also exhibited a bias to initially look towards the drug-paired stimuli at the first post-test session, but not thereafter. Subjects who experienced more positive subjective drug effects during conditioning exhibited a smaller decline in preference during the extinction phase. Further, longer inter-session intervals during the extinction phase were associated with less extinction of the behavioral preference measure. Conditioned responses after two pairings with MA extinguish quickly, and are influenced by both subjective drug effects and the extinction interval. Characterizing and refining this conditioning procedure will aid in understanding the acquisition and extinction processes of drug-related conditioned responses in humans.

  5. The speed of learning instructed stimulus-response association rules in human: experimental data and model.

    Science.gov (United States)

    Bugmann, Guido; Goslin, Jeremy; Duchamp-Viret, Patricia

    2013-11-06

    Humans can learn associations between visual stimuli and motor responses from just a single instruction. This is known to be a fast process, but how fast is it? To answer this question, we asked participants to learn a briefly presented (200ms) stimulus-response rule, which they then had to rapidly apply after a variable delay of between 50 and 1300ms. Participants showed a longer response time with increased variability for short delays. The error rate was low and did not vary with the delay, showing that participants were able to encode the rule correctly in less than 250ms. This time is close to the fastest synaptic learning speed deemed possible by diffusive influx of AMPA receptors. Learning continued at a slower pace in the delay period and was fully completed in average 900ms after rule presentation onset, when response latencies dropped to levels consistent with basic reaction times. A neural model was proposed that explains the reduction of response times and of their variability with the delay by (i) a random synaptic learning process that generates weights of average values increasing with the learning time, followed by (ii) random crossing of the firing threshold by a leaky integrate-and-fire neuron model, and (iii) assuming that the behavioural response is initiated when all neurons in a pool of m neurons have fired their first spike after input onset. Values of m=2 or 3 were consistent with the experimental data. The proposed model is the simplest solution consistent with neurophysiological knowledge. Additional experiments are suggested to test the hypothesis underlying the model and also to explore forgetting effects for which there were indications for the longer delay conditions. This article is part of a Special Issue entitled Neural Coding 2012. © 2013 Elsevier B.V. All rights reserved.

  6. Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.

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    Edwin Choy

    2008-11-01

    Full Text Available Lymphoblastoid cell lines (LCLs, originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance--i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding.

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

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    Dai, Jiawen [Molecular Radiobiology Laboratory, Division of Cellular and Molecular Research (Singapore); Itahana, Koji, E-mail: koji.itahana@duke-nus.edu.sg [Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School (Singapore); Baskar, Rajamanickam, E-mail: r.baskar@nccs.com.sg [Molecular Radiobiology Laboratory, Division of Cellular and Molecular Research (Singapore); Department of Radiation Oncology, National Cancer Centre (Singapore)

    2015-02-27

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

  8. Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

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    Alexandre Lehmann

    Full Text Available Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.

  9. Kiwifruit Non-Sugar Components Reduce Glycaemic Response to Co-Ingested Cereal in Humans

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    Suman Mishra

    2017-10-01

    Full Text Available Kiwifruit (KF effects on the human glycaemic response to co-ingested wheat cereal were determined. Participants (n = 20 consumed four meals in random order, all being made to 40 g of the same available carbohydrate, by adding kiwifruit sugars (KF sug; glucose, fructose, sucrose 2:2:1 to meals not containing KF. The meals were flaked wheat biscuit (WB+KFsug, WB+KF, WB+guar gum+KFsug, WB+guar gum+KF, that was ingested after fasting overnight. Blood glucose was monitored 3 h and hunger measured at 180 min post-meal using a visual analogue scale. KF and guar reduced postprandial blood glucose response amplitude, and prevented subsequent hypoglycaemia that occurred with WB+KFsug. The area between the blood glucose response curve and baseline from 0 to 180 min was not significantly different between meals, 0–120 min areas were significantly reduced by KF and/or guar. Area from 120 to 180 min was positive for KF, guar, and KF+guar, while the area for the WB meal was negative. Hunger at 180 min was significantly reduced by KF and/or guar when compared with WB. We conclude that KF components other than available carbohydrate may improve the glycaemic response profile to co-ingested cereal food.

  10. Children’s rights and human trafficking and responsible parenthood in west african country nigeria.

    Directory of Open Access Journals (Sweden)

    Abba Joebarth

    2014-06-01

    Full Text Available Every child has right to life and if so, it is a responsible parent that could make this workable and realistic to uphold the children’s rights and existence to life. Time is now ripped for the society to look into the Children`s Rights and Human Trafficking and Responsible Parents in Western African country Nigeria.  Children have the natural rights to exist, grow maturely and to develop in whichever hemisphere or environment they find themselves. A good child born to a good and responsible parent ought not and should not encounter or experience in anyway the so called children’s problem through one´s  good mother and father’s care in any family. We are to peruse here the issue concerning the West African Nigerian child’s rights a responsible parent. On why a child’s rights should not be violated or trampled upon; the expected parental duties, neglect of a child’s education and upbringing, child’s trafficking, malnutrition and maltreatment sagas, the harms with street children and various problems which different children encounter are what this article is all about.  We shall base our knowledge here basically on descriptive, analytical and evaluative methods.  The issues of solution, suggestions and remedies and the way forward are looked into for the better society of the present era.

  11. Cortically evoked responses of human pallidal neurons recorded during stereotactic neurosurgery.

    Science.gov (United States)

    Nishibayashi, Hiroki; Ogura, Mitsuhiro; Kakishita, Koji; Tanaka, Satoshi; Tachibana, Yoshihisa; Nambu, Atsushi; Kita, Hitoshi; Itakura, Toru

    2011-02-15

    Responses of neurons in the globus pallidus (GP) to cortical stimulation were recorded for the first time in humans. We performed microelectrode recordings of GP neurons in 10 Parkinson's disease (PD) patients and 1 cervical dystonia (CD) patient during surgeries to implant bilateral deep brain stimulation electrodes in the GP. To identify the motor territories in the external (GPe) and internal (GPi) segments of the GP, unitary responses evoked by stimulation of the primary motor cortex were observed by constructing peristimulus time histograms. Neurons in the motor territories of the GPe and GPi responded to cortical stimulation. Response patterns observed in the PD patients were combinations of an early excitation, an inhibition, and a late excitation. In addition, in the CD patient, a long-lasting inhibition was prominent, suggesting increased activity along the cortico-striato-GPe/GPi pathways. The firing rates of GPe and GPi neurons in the CD patient were lower than those in the PD patients. Many GPe and GPi neurons of the PD and CD patients showed burst or oscillatory burst activity. Effective cathodal contacts tended to be located close to the responding neurons. Such unitary responses induced by cortical stimulation may be of use to target motor territories of the GP for stereotactic functional neurosurgery. Future findings utilizing this method may give us new insights into understanding the pathophysiology of movement disorders. Copyright © 2011 Movement Disorder Society.

  12. Mediators of compassionate goal intervention effects on human neuroendocrine responses to the Trier Social Stress Test.

    Science.gov (United States)

    Erickson, Thane M; Mayer, Stefanie E; Lopez-Duran, Nestor L; Scarsella, Gina M; McGuire, Adam P; Crocker, Jennifer; Abelson, James L

    2017-11-01

    The hypothalamic-pituitary-adrenal (HPA) axis is thought to mediate the effects of stress on illness. Research has identified a limited number of psychological variables that modulate human HPA responses to stressors (e.g. perceived control and social support). Prosocial goals can reduce subjective stress, but have not been carefully examined in experimental settings where pathways of impact on biological stress markers may be traced. Recent work demonstrated that coaching individuals to strive to help others reduced HPA responses to the Trier Social Stress Test (TSST) relative to other cognitive interventions. However, identification of mediational pathways, which were not examined in the original study, is necessary to determine whether the HPA buffering effects were due to helping motivations (compassionate goals; CGs) rather than via previously identified variables such as control or support. In this new analysis, we combined the original cortisol data with novel observer ratings of interpersonal behavior and psychological variables during the stress task, and conducted new, theory-driven analyses to determine psychological mediators for the intervention's effect on cortisol responses (N = 54; 21 females, 33 males; 486 cortisol samples). Control, support, and task ego-threat failed to account for the effects of the intervention. As hypothesized, self and observer-rated CGs, as well as observer-rated perceptions of participants' interpersonal behavior as morally desirable (but not as dominant or affiliative) were significant mediators of neuroendocrine responses. The findings suggest that stress-reduction interventions based on prosocial behavior should target particular motivational and interpersonal features.

  13. Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice.

    Science.gov (United States)

    Miao, Carol H; Ye, Peiqing; Thompson, Arthur R; Rawlings, David J; Ochs, Hans D

    2006-07-01

    A robust humoral immune response against human factor VIII (hFVIII) following naked DNA transfer into immunocompetent hemophilia A mice completely inhibits circulating FVIII activity despite initial high-level hFVIII gene expression. To prevent this undesirable response, we compared transient immunomodulation strategies. Eight groups of mice (n = 4-9 per group) were treated with naked DNA transfer of pBS-HCRHPI-hFVIIIA simultaneously with immunosuppressive reagents that included cyclosporine A (CSA), rapamycin (RAP), mycophenylate mofetil (MMF), a combination of CSA and MMF, a combination of RAP and MMF, a monoclonal antibody against murine CD40 ligand (MR1), recombinant murine Ctla4Ig, and a combination of MR1 and Ctla4Ig. All animals except those receiving only CSA exhibited delayed or absent immune responses against hFVIII. The most effective immunosuppressive regimen, the combination of Ctla4Ig and MR1, prevented inhibitor formation in 8 of 9 animals; the ninth had transient low-titer antibodies. All 9 mice of this group produced persistent, therapeutic levels of hFVIII for more than 6 months. When challenged with the T-dependent antigen bacteriophage Phix174, tolerized mice exhibited normal primary and secondary antibody responses, suggesting that transient immunomodulation to disrupt B/T-cell interaction at the time of plasmid injection effectively promoted long-term immune tolerance specific for hFVIII.

  14. Common cortical responses evoked by appearance, disappearance and change of the human face

    Directory of Open Access Journals (Sweden)

    Kida Tetsuo

    2009-04-01

    Full Text Available Abstract Background To segregate luminance-related, face-related and non-specific components involved in spatio-temporal dynamics of cortical activations to a face stimulus, we recorded cortical responses to face appearance (Onset, disappearance (Offset, and change (Change using magnetoencephalography. Results Activity in and around the primary visual cortex (V1/V2 showed luminance-dependent behavior. Any of the three events evoked activity in the middle occipital gyrus (MOG at 150 ms and temporo-parietal junction (TPJ at 250 ms after the onset of each event. Onset and Change activated the fusiform gyrus (FG, while Offset did not. This FG activation showed a triphasic waveform, consistent with results of intracranial recordings in humans. Conclusion Analysis employed in this study successfully segregated four different elements involved in the spatio-temporal dynamics of cortical activations in response to a face stimulus. The results show the responses of MOG and TPJ to be associated with non-specific processes, such as the detection of abrupt changes or exogenous attention. Activity in FG corresponds to a face-specific response recorded by intracranial studies, and that in V1/V2 is related to a change in luminance.

  15. Unsupervised feature learning improves prediction of human brain activity in response to natural images.

    Directory of Open Access Journals (Sweden)

    Umut Güçlü

    2014-08-01

    Full Text Available Encoding and decoding in functional magnetic resonance imaging has recently emerged as an area of research to noninvasively characterize the relationship between stimulus features and human brain activity. To overcome the challenge of formalizing what stimulus features should modulate single voxel responses, we introduce a general approach for making directly testable predictions of single voxel responses to statistically adapted representations of ecologically valid stimuli. These representations are learned from unlabeled data without supervision. Our approach is validated using a parsimonious computational model of (i how early visual cortical representations are adapted to statistical regularities in natural images and (ii how populations of these representations are pooled by single voxels. This computational model is used to predict single voxel responses to natural images and identify natural images from stimulus-evoked multiple voxel responses. We show that statistically adapted low-level sparse and invariant representations of natural images better span the space of early visual cortical representations and can be more effectively exploited in stimulus identification than hand-designed Gabor wavelets. Our results demonstrate the potential of our approach to better probe unknown cortical representations.

  16. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

    Directory of Open Access Journals (Sweden)

    Howard Y Chang

    2004-02-01

    Full Text Available Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas.

  17. The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans

    Directory of Open Access Journals (Sweden)

    Kasper W. ter Horst

    2017-11-01

    Conclusions: Fructose ingestion in obese humans stimulates FGF21 secretion, and this response is related to systemic metabolism. Further studies are needed to establish if FGF21 signaling is (pathophysiologically involved in fructose metabolism and metabolic health.

  18. Effect of various pre-crash braking strategies on simulated human kinematic response with varying levels of driver attention

    NARCIS (Netherlands)

    Rooij, L. van

    2011-01-01

    In this study, human kinematic response resulting from various pre-crash braking scenarios is quantified. The underlying question is what kind of effect do pre-crash braking systems have on the driver or the front seat passenger.

  19. Combining Human Computing and Machine Learning to Make Sense of Big (Aerial) Data for Disaster Response.

    Science.gov (United States)

    Ofli, Ferda; Meier, Patrick; Imran, Muhammad; Castillo, Carlos; Tuia, Devis; Rey, Nicolas; Briant, Julien; Millet, Pauline; Reinhard, Friedrich; Parkan, Matthew; Joost, Stéphane

    2016-03-01

    Aerial imagery captured via unmanned aerial vehicles (UAVs) is playing an increasingly important role in disaster response. Unlike satellite imagery, aerial imagery can be captured and processed within hours rather than days. In addition, the spatial resolution of aerial imagery is an order of magnitude higher than the imagery produced by the most sophisticated commercial satellites today. Both the United States Federal Emergency Management Agency (FEMA) and the European Commission's Joint Research Center (JRC) have noted that aerial imagery will inevitably present a big data challenge. The purpose of this article is to get ahead of this future challenge by proposing a hybrid crowdsourcing and real-time machine learning solution to rapidly process large volumes of aerial data for disaster response in a time-sensitive manner. Crowdsourcing can be used to annotate features of interest in aerial images (such as damaged shelters and roads blocked by debris). These human-annotated features can then be used to train a supervised machine learning system to learn to recognize such features in new unseen images. In this article, we describe how this hybrid solution for image analysis can be implemented as a module (i.e., Aerial Clicker) to extend an existing platform called Artificial Intelligence for Disaster Response (AIDR), which has already been deployed to classify microblog messages during disasters using its Text Clicker module and in response to Cyclone Pam, a category 5 cyclone that devastated Vanuatu in March 2015. The hybrid solution we present can be applied to both aerial and satellite imagery and has applications beyond disaster response such as wildlife protection, human rights, and archeological exploration. As a proof of concept, we recently piloted this solution using very high-resolution aerial photographs of a wildlife reserve in Namibia to support rangers with their wildlife conservation efforts (SAVMAP project, http://lasig.epfl.ch/savmap ). The

  20. Immune response after neonatal transfer of a human factor IX-expressing retroviral vector in dogs, cats, and mice.

    Science.gov (United States)

    Xu, Lingfei; Mei, Manxue; Haskins, Mark E; Nichols, Timothy C; O'donnell, Patricia; Cullen, Karyn; Dillow, Aaron; Bellinger, Dwight; Ponder, Katherine P

    2007-01-01

    Gene therapy could prevent bleeding in hemophilia. However, antibodies could inhibit coagulation, while cytotoxic T lymphocytes could destroy modified cells. The immaturity of the newborn immune system might prevent these immune responses from occurring after neonatal gene therapy. Newborn dogs, cats, or mice were injected intravenously with a retroviral vector expressing human Factor IX. Plasma was evaluated for antigen and anti-human Factor IX antibodies. Cytotoxic T lymphocyte responses were evaluated indirectly by analysis of retroviral vector RNA in liver. Lymphocytes were evaluated for cytokine secretion and the ability to suppress an immune response to human Factor IX in mice. Hemophilia B dogs that achieved 942+/-500 ng/ml (19% normal) or 5+/-0.4 ng/ml (0.1% normal) of human Factor IX in plasma only bled 0 or 1.2 times per year, respectively, and were tolerant to infusion of human Factor IX. Normal cats expressed human Factor IX at 118+/-29 ng/ml (2% normal) in plasma without antibody formation. However, plasma human Factor IX disappeared at late times in 1 of 4 cats, which was probably due to a cytotoxic T lymphocyte response that destroyed cells with high expression. C3H mice were tolerant to human Factor IX after neonatal gene therapy, which may involve clonal deletion of human Factor IX-responsive cells. These data demonstrate that neonatal gene therapy does not induce antibodies to human Factor IX in dogs, cats, or mice. The putative cytotoxic T lymphocyte response in one cat requires further study.

  1. Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.

    Science.gov (United States)

    Liang, Christine L; Ances, Beau M; Perthen, Joanna E; Moradi, Farshad; Liau, Joy; Buracas, Giedrius T; Hopkins, Susan R; Buxton, Richard B

    2013-01-01

    The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of unde